US 2006O122243A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0122243 A1 Muto et al. (43) Pub. Date: Jun. 8, 2006

(54) ANTIALLERGIC teromyoma which comprises as an active ingredient a Sub stance selected from the group consisting of a compound (76) Inventors: Susumu Muto, Tokyo (JP); Akiko Itai, represented by the following general formula (I) and a Tokyo (JP) pharmacologically acceptable salt thereof, and a hydrate Correspondence Address: thereof and a solvate thereof: GREENBLUM & BERNSTEIN, P.L.C. 1950 ROLAND CLARKE PLACE RESTON, VA 20191 (US) (I) (21) Appl. No.: 10/515,623 (22) PCT Filed: Jun. 5, 2003 (86). PCT No.: PCT/UP03/07120 (30) Foreign Application Priority Data wherein X represents a connecting group whose number of Jun. 6, 2002 (JP)...... 2002-165148 atoms in the main chain is 2 to 5 (said connecting group may be substituted). A represents hydrogen atom or acetyl group, Publication Classification E represents an aryl group which may be substituted or a hetero aryl group which may be substituted, ring Z repre (51) Int. Cl. A6 IK 3/426 (2006.01) sents an arene which may have one or more Substituents in A6 IK 3L/65 (2006.01) addition to the group represented by formula—O-A wherein C07D 277/34 (2006.01) A has the same meaning as that defined above and the group CD7C 235/40 (2006.01) represented by formula —X-E wherein each of X and E has (52) U.S. Cl...... 514/369; 514/620: 514/621; the same meaning as that defined above, or a heteroarene 548/183: 564/167 which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the (57) ABSTRACT same meaning as that defined above and the group repre A medicament for the preventive and/or therapeutic treat sented by formula —X-E wherein each of X and E has the ment of allergic diseases and/or endometriosis and/or hys same meaning as that defined above. Patent Application Publication Jun. 8, 2006 Sheet 1 of 2 US 2006/0122243 A1

70

60 -- Diluent -e- Test comp. 50

3 O

Pre 30 60 120 240 360 480 1440 Time (min) Patent Application Publication Jun. 8, 2006 Sheet 2 of 2 US 2006/O122243 A1

-- inhibitor -O-- Placebo

250 -- inhibitor -O- Placebo 2OO

150

OO

SO

Pre Post US 2006/0122243 A1 Jun. 8, 2006

ANTIALLERGIC 0005 Therefore, an antiallergic drug, which strongly inhibits activation of mast cells and can be used as a FIELD OF INVENTION therapeutic agent for radical treatment of allergic diseases, is 0001. The present invention relates to pharmaceutical usable as an effective therapeutic agent for endometriosis. compositions effective for preventive and/or therapeutic 0006 45% of patients with endometriosis are suffered treatment of allergic diseases such as pollinosis, bronchial from hysteromyoma, which suggests a relation of hyster asthma, atopic dermatitis, urticaria; endometriosis, and hys omyoma and allergy in the same manner as endometriosis. teromyoma. Accordingly, it is highly probable that an antiallergic agent, which can be used as a therapeutic agent for radical treat BACKGROUND ART ment of allergic diseases, is useful as a therapeutic agent for 0002 Allergic diseases are understood to be caused by hysteromyoma. production of IgE by an antigen stimulation invaded in a 0007 N-phenylsalicylamide derivatives are disclosed as body, and Successive release of various chemical mediators Such as inflammatory cytokine, histamine, leukotriene and a plant growth inhibitor in the specification of U.S. Pat. the like by a degranulation from an activated mast cell No.4,358,443. As medicaments, said derivatives are dis stimulated by a complex of the antigen and IgE, thereby closed as anti-inflammatory agents in the specification of constriction of airway, accentuation of vascular permeabil European Patent No. 0.221.211, Japanese Patent Unexam ity, inflammation of skin, bronchi and the like are induced. ined Publication (KOKAI) No. (Sho)62-99329, and the Accordingly, antiallergic agents are understood mainly as specification of U.S. Pat. No. 6,117,859. Furthermore, they drugs inhibiting allergic reaction type I and Successively are disclosed as NF-K B inhibitors in the pamphlets of induced allergic inflammation, particularly as drugs inhib International Publication WO99/65499, International Publi iting the production and release of the mediators from mast cation WO02/49632, and International Publication WO02/ cells, or those as being antagonists against the aforemen 076918, and as inhibitors against the production of cytok tioned actions. At present, steroids, antihistaminic drugs, ines in the pamphlet of International Publication WO02/ suppressants or inhibitors of the release of mediators and the O51397. like have been used as antiallergic agents. Although steroids are very effective drugs, they have a problem of side effects. DISCLOSURE OF THE INVENTION Antihistaminic drugs are only for symptomatic therapies and fail to achieve radical therapy. Suppressants or inhibitors of 0008 An object of the present invention is to provide the release of mediators are considered to have a high medicaments that enable radical preventive and/or therapeu effectiveness. However, some of them lack immediate effec tic treatment of allergy by an inhibition of allergic reactions. tiveness or have central side effects. Accordingly, the anti To achieve the aforementioned object, the inventors of the allergic drugs currently available are not fully satisfactory as present invention conducted various researches on the anti they are. allergic actions of salicylamide derivatives which are gen erally believed to have low toxicity. As a result, they found 0003 Patients with endometriosis are increasing in recent that N-substituted salicylamide derivatives, particularly years, and currently, 10 to 14% of females are considered to N-arylsalicylamide derivatives, specifically N-phenylsalicy be suffered from the disease. Endometriosis has been lamide derivatives wherein aniline moiety is substituted in focused as a cause of sterility, as well as the disease lowers both of 2- and 5-positions or in both of 3- and 5-positions, the quality of life of patients with severe pains during and N-thiazol-2-yl-salicylamide derivatives wherein thiaz menstruation and coitus. For a treatment of the disease, a therapy by using a hormone drug has been currently applied ole ring is substituted in both of 4- and 5-positions have as a pseudo menopausal therapy. However, the aforemen extremely Superior activity in inhibitory action against the tioned therapy induces strong side effects, and it also has a proliferation of mast cells, inhibitory action against the risk of causing osteoporosis during a long-term administra degranulation from mast cells by antigen and IgE stimula tion. Therefore, at present, a drug or a method for treatment tion, and inhibitory action against the production of IgE with safety and high efficacy is not available. from activated B cells, and that radical preventive and/or therapeutic treatment of allergic diseases can be achieved. 0004. In recent years, it was found that mast cells exist The inventors also conducted researches on hydroxyaryl apparently with high density in the lesion of endometriosis derivatives which are analogous compounds thereof. The (American Journal of Reproductive Immunology (New present invention was achieved on the basis of these find York: 1998), (Denmark), Vol. 40, No. 4, p. 291-294), and 1ngS. that mast cells are activated to lead degranulation (Nikkei Medical, 2002, No. 415, p. 28; Fertility and Sterility, (USA), 0009. The present invention thus provides: 2002, Vol. 78, No. 4, p. 782-786). Furthermore, a relation between endometriosis and allergy is strongly suggested, 0010 (1) A medicament for preventive and/or therapeutic because interstitial hyperplasia, which is a major step of treatment of allergic diseases and/or endometriosis and/or infiltration and lesion of mast cells, is significantly inhibited hysteromyoma which comprises as an active ingredient a by the administration of a leukotriene antagonist having Substance selected from the group consisting of a com antiallergic action to an endometriosis model rat (Nikkei pound represented by the following general formula (I) Medical, 2002, No. 415, p. 28; Fertility and Sterility, (USA), and a pharmacologically acceptable Salt thereof, and a 2002, Vol. 78, No. 4, p. 782-786). hydrate thereof and a solvate thereof: US 2006/0122243 A1 Jun. 8, 2006

-continued -C=N-N-C-, -N-C-N-, (I) | || | || | H H. O H. O. H H -C-N-N-C-, -C-N-N-C-, | O H H O O H. H. H. -C-O-, -C-N-N- | | 0.011 wherein X represents a connecting group whose O O H. H. p g group S number of atoms in a main chain is 2 to 5 (said connecting group may be substituted), -C=N-N-, X--- 0012. A represents hydrogen atom or acetyl group, H H u? H.| O|| H 0013 E represents an aryl group which may be substi O tuted or a heteroaryl group which may be substituted, N 0014 ring Z represents an arene which may have one or N-C- more Substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one 0018 wherein a bond at the left end binds to ring Z and or more substituents in addition to the group represented a bond at the right end binds to E: by formula —O-A wherein A has the same meaning as 0019 (3) the aforementioned medicament which com that defined above and the group represented by formula prises as an active ingredient a Substance selected from —X-E wherein each of X and E has the same meaning as the group consisting of the compound and a pharmaco that defined above. logically acceptable salt thereof, and a hydrate thereof and 00.15 Examples of preferred medicaments provided by a solvate thereof, wherein X is a group represented by the the present invention include: following formula (said group may be substituted): 0016 (2) the aforementioned medicament which com prises as an active ingredient a substance selected from the group consisting of the compound and a pharmaco -C-N- logically acceptable Salt thereof, and a hydrate thereof and O H a solvate thereof, wherein X is a group selected from the following connecting group C. (said group may be Sub stituted): 0020 wherein a bond at the left end binds to ring Z and 0017 Connecting group C. The groups of the following a bond at the right end binds to E: formulas: 0021 (4) the aforementioned medicament which com prises as an active ingredient a Substance selected from the group consisting of the compound and a pharmaco logically acceptable Salt thereof, and a hydrate thereof and | a solvate thereof, wherein A is a hydrogen atom; -C-N-, -C-N-C-, | | | | 0022 (5) the aforementioned medicament which com O H O H. H. prises as an active ingredient a Substance selected from the group consisting of the compound and a pharmaco logically acceptable Salt thereof, and a hydrate thereof and -C-N-C-C-, -C-C-C-, | | | | | a Solvate thereof, wherein ring Z is a C to Co. arene O H. H. H. O H. H. which may have one or more Substituents in addition to H H O the group represented by formula —O-A wherein A has the same meaning as that defined in the general formula -C-C=C-, -C=C-, -S-N- | | (I) and the group represented by formula —X-E wherein O H H O H each of X and E has the same meaning as that defined in O H the general formula (I), or a 5 to 13-membered het | eroarene which may have one or more Substituents in -N-C-, -N-S-, -C-N-, addition to the group represented by formula —O-A | || | || wherein A has the same meaning as that defined in the H. O H. O H. H. general formula (I) and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined in the general formula (I); 0023 (6) the aforementioned medicament which com prises as an active ingredient a Substance selected from US 2006/0122243 A1 Jun. 8, 2006

the group consisting of the compound and a pharmaco the group consisting of the compound and a pharmaco logically acceptable Salt thereof, and a hydrate thereof and logically acceptable Salt thereof, and a hydrate thereof and a Solvate thereof, wherein ring Z is a ring selected from a solvate thereof, wherein E is 3,5-bis(trifluorometh the following ring group B: yl)phenyl group; 0024 Ring Group f benzene ring, naphthalene ring, 0032 (13) the aforementioned medicament which com thiophene ring, pyridine ring, indole ring, quinoxaline prises as an active ingredient a Substance selected from ring, and carbazole ring the group consisting of the compound and a pharmaco 0.025 wherein said ring may have one or more substitu logically acceptable Salt thereof, and a hydrate thereof and ents in addition to the group represented by formula a solvate thereof, wherein E is a 5-membered heteroaryl —O-A wherein A has the same meaning as that defined in group which may be substituted. the general formula(I) and the group represented by 0033. From another aspect, the present invention pro formula —X-E wherein each of X and E has the same vides use of each of the aforementioned substances for meaning as that defined in the general formula (I); manufacture of the medicament according to the aforemen 0026 (7) the aforementioned medicament which com tioned (1) to (13). prises as an active ingredient a substance selected from 0034. The present invention further provides a method the group consisting of the compound and a pharmaco for preventive and/or therapeutic treatment of allergic dis logically acceptable Salt thereof, and a hydrate thereof and eases and/or endometriosis and/or hysteromyoma in a mam a solvate thereof, wherein ring Z is a benzene ring which mal including a human, which comprises the step of admin may have one or more Substituents in addition to the istering preventively and/or therapeutically effective amount group represented by formula —O-A wherein A has the of the aforementioned substances to a mammal including a same meaning as that defined in the general formula (I) human. and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined in 0035) The present invention further provides: the general formula (I); 0036 (1) a compound represented by the general formula 0027 (8) the aforementioned medicament which com (I-1) or a salt thereof, or a hydrate thereof or a solvate prises as an active ingredient a substance selected from thereof: the group consisting of the compound and a pharmaco logically acceptable salt thereof, and a hydrate thereof and a solvate thereof, wherein ring Z is a benzene ring which (I-1) is Substituted with halogen atom(s) in addition to the group represented by formula —O-A wherein A has the same meaning as that defined in the general formula (I) and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined in the general formula (I); 0028 (9) the aforementioned medicament which com 0037 wherein Z' represents 2-hydroxyphenyl group prises as an active ingredient a substance selected from which may be substituted in the 5-position or 2-acetox the group consisting of the compound and a pharmaco yphenyl group which may be substituted in the 5-position, logically acceptable Salt thereof, and a hydrate thereof and and E' represents a phenyl group which may be substi a solvate thereof, wherein ring Z is a naphthalene ring tuted. which may have one or more Substituents in addition to 0038 Preferably, provided is: the group represented by formula —O-A wherein A has the same meaning as that defined in the general formula 0039 (2) the compound or a salt thereof, or a hydrate (I) and the group represented by formula —X-E wherein thereof or a solvate thereof, wherein E' is 2.5-bis(trifluo each of X and E has the same meaning as that defined in romethyl)phenyl group or 3.5-bis(trifluoromethyl)phenyl the general formula (I); group, except that the following compounds are excluded: 0029 (10) the aforementioned medicament which com 0040 N-3,5-bis(trifluoromethyl)phenyl-2-hydroxyben prises as an active ingredient a substance selected from Zamide, the group consisting of the compound and a pharmaco 0041 N-3,5-bis(trifluoromethyl)phenyl-5-chloro-2-hy logically acceptable Salt thereof, and a hydrate thereof and droxybenzamide, a Solvate thereof, wherein E is a C to Co aryl group which may be substituted or a 5 to 13-membered het 0042 N-3,5-bis(trifluoromethyl)phenyl-5-bromo-2-hy eroaryl group which may be substituted; droxybenzamide, 0030 (11) the aforementioned medicament which com 0043 N-3,5-bis(trifluoromethyl)phenyl-2-hydroxy-5- prises as an active ingredient a substance selected from iodobenzamide, and the group consisting of the compound and a pharmaco 0044) N-3,5-bis(trifluoromethyl)phenyl-2-hydroxy-5- logically acceptable Salt thereof, and a hydrate thereof and nitrobenzamide. a Solvate thereof, wherein E is a phenyl group which may be substituted; 0045 More preferably, provided is: 0031 (12) the aforementioned medicament which com 0046 (3) the compound or a salt thereof, or a hydrate prises as an active ingredient a substance selected from thereof or a solvate thereof, wherein Z' is 2-hydroxyphe US 2006/0122243 A1 Jun. 8, 2006

nyl group which is Substituted with a halogen atom in the 5-position or 2-acetoxyphenyl group which is substituted with a halogen atom in the 5-position. (I-3) 0047 Moreover, the present invention provides: 0.048 (1) a compound represented by the general formula (I-2) or a salt thereof, or a hydrate thereof or a solvate thereof: 0062) wherein Z represents 2-hydroxyphenyl group which may be substituted in the 5-position or 2-acetox (I-2) yphenyl group which may be substituted in the 5-position, O E represents a group represented by the following for mula: Z2 ls E2

H

0049) wherein Z represents 2-hydroxyphenyl group which may be substituted in the 5-position or 2-acetox yphenyl group which may be substituted in the 5-position, E represents a 2,5-di-substituted phenyl group wherein one of said Substituents is trifluoromethyl group or a 0063 wherein one of R and R represents hydrogen 3,5-di-substituted phenyl group wherein one of said sub atom and the other represents a hydrocarbon group which stituents is trifluoromethyl group, provided that the fol may be substituted or hydroxyl group which may be lowing compounds are excluded: Substituted, and 0050 5-chloro-N-5-chloro-3-(trifluoromethyl)phenyl 0064) R' represents a C to C. hydrocarbon group 2-hydroxybenzamide, which may be substituted. 0065 Preferably, provided is: 0051 5-fluoro-2-hydroxy-N-2-(2.2.2-trifluoroethoxy)- 0066 (2) the compound according to claim 18 or a salt 5-(trifluoromethyl)phenylbenzamide, thereof, or a hydrate thereof or a solvate thereof, wherein Z is 2-hydroxyphenyl group which is substituted with a 0.052 5-fluoro-2-hydroxy-N-2-(6,6,6-trifluorohexy halogen atom in the 5-position or 2-acetoxyphenyl group loxy)-5-(trifluoromethyl)phenyl-benzamide, which is substituted with a halogen atom in the 5-position. 0053 5-chloro-N-2-(4-chlorophenoxy)-5-(trifluorom 0067. The present invention also provides: ethyl)phenyl-2-hydroxybenzamide, 0068 (1) a compound represented by the general formula (I-4) or a salt thereof, or a hydrate thereof or a solvate 0054 5-chloro-2-hydroxy-N-2-(4-methylphenoxy)-5- thereof: (trifluoromethyl)phenylbenzamide, (I-4) 0.055 5-chloro-N-2-(4-chlorophenyl)sulfanyl-5-(trifluo O romethyl)phenyl-2-hydroxybenzamide, 4 0056 5-chloro-2-hydroxy-N-2-(1-naphthyloxy)-5-(trif --- luoromethyl)phenylbenzamide, and H 0057 5-chloro-2-hydroxy-N-2-(2-naphthyloxy)-5-(trif 0069 wherein Z represents 2-hydroxyphenyl group luoromethyl)phenylbenzamide. which may be substituted in the 5-position or 2-acetox yphenyl group which may be substituted in the 5-position, 0.058 Preferably, provided is: E" represents a group represented by the following for 0059 (2) the compound or a salt thereof, or a hydrate mula: thereof or a solvate thereof, wherein Z is 2-hydroxyphe nyl group which is Substituted with a halogen atom in the 5-position or 2-acetoxyphenyl group which is substituted with a halogen atom in the 5-position. - C 0060 Moreover, the present invention provides: 0070 wherein R represents a hydrocarbon group 0061 (1) a compound represented by the general formula which may be substituted, R“represents a halogenatom, (I-3) or a salt thereof, or a hydrate thereof or a solvate cyano group, an acyl group which may be substituted, or thereof: a heterocyclic group which may be substituted. US 2006/0122243 A1 Jun. 8, 2006

0071 Preferably, provided is: en-1-yl, hex-4-en-1-yl, hex-5-en-1-yl 4-methylpent-3-en-1- y1. 4-methylpent-3-en-1-yl, hept-1-en-1-yl, hept-6-en-1-yl, 0072 (2) the compound or a salt thereof, or a hydrate oct-1-en-1-yl, oct-7-en-1-yl. non-1-en-1-yl, non-8-en-1-yl, thereof or a solvate thereof, wherein Z is 2-hydroxyphe dec-1-en-1-yl, dec-9-en-1-yl, undec-1-en-1-yl, undec-10-en nyl group which is Substituted with a halogen atom in the 1-yl, dodec-1-en-1-yl, dodec-11-en-1-yl, tridec-1-en-1-yl, 5-position or 2-acetoxyphenyl group which is substituted tridec-12-en-1-yl, tetradec-1-en-1-yl, tetradec-13-en-1-yl, with a halogen atom in the 5-position. pentadec-1-en-1-yl, and pentadec-14-en-1-yl, which are C to Cs straight chain or branched chain alkenyl groups. BRIEF EXPLANATION OF THE DRAWINGS 0082) Examples of the alkynyl group include, for 0073 FIG. 1 shows inhibitory effect of the medicament example, ethynyl, prop-1-yn-1-yl, prop-2-yn-1-yl, but-1-yn of the present invention (compound No. 50) against imme 1-yl, but-3-yn-1-yl, 1-methylprop-2-yn-1-yl, pent-1-yn-1-yl, diate type allergy. pent-4-yn-1-yl, hex-1-yn-1-yl, hex-5-yn-1-yl, hept-1-yn-1- yl, hept-6-yn-1-yl, oct-1-yn-1-yl, oct-7-yn-1-yl, non-1-yn 0074 FIG. 2 shows inhibitory effect of the medicament 1-yl. non-8-yn-1-yl, dec-1-yn-1-yl, dec-9-yn-1-yl, undec-1- of the present invention (compound No. 50) against derma yn-1-yl, undec-10-yn-1-yl, dodec-1-yn-1-yl, dodec-11-yn-1- titis with an atopic dermatitis model. yl, tridec-1-yn-1-yl, tridec-12-yn-1-yl, tetradec-1-yn-1-yl, tetradec-13-yn-1-yl, pentadec-1-yn-1-yl, and pentadec-14 BEST MODE FOR CARRYING OUT THE yn-1-yl, which are C to Cs straight chain or branched chain INVENTION alkynyl groups. 0075) Reference to the disclosure of the pamphlet of 0083. Examples of the alkylene group include, for International Publication WOO2/49632 is useful for better example, methylene, ethylene, ethane-1,1-diyl, propane-1, understanding of the present invention. The entire disclosure 3-diyl, propane-1,2-diyl, propane-2,2-diyl, butane-1,4-diyl. of the aforementioned pamphlet of International Publication pentane-1,5-diyl, hexane-1,6-diyl, and 1,1,4,4-tetrameth WO02/49632 is incorporated by reference in the disclosures ylbutane-1,4-diyl group, which are C to Cs straight chain or of the present specification. branched chain alkylene groups. 0.076 The terms used in the present specification have the 0084 Examples of the alkenylene group include, for following meanings. example, ethene-1,2-diyl, propene-1,3-diyl, but-1-ene-1,4- 0077. As the halogenatom, any of fluorine atom, chlorine diyl, but-2-ene-1,4-diyl, 2-methylpropene-1,3-diyl, pent-2- atom, bromine atom, or iodine atom may be used unless ene-1,5-diyl, and hex-3-ene-1,6-diyl, which are C to C. otherwise specifically referred to. straight chain or branched chain alkylene groups. 0078 Examples of the hydrocarbon group include, for 0085 Examples of the alkylidene group include, for example, an aliphatic hydrocarbon group, an aryl group, an example, methylidene, ethylidene, propylidene, isopropy arylene group, an aralkyl group, a bridged cyclic hydrocar lidene, butylidene, pentylidene, and hexylidene, which are bon group, a spiro cyclic hydrocarbon group, and a terpene C, to Co straight chain or branched chain alkylidene groups. hydrocarbon. 0086 Examples of the cycloalkyl group include, for 0079 Examples of the aliphatic hydrocarbon group example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, include, for example, alkyl group, alkenyl group, alkynyl cycloheptyl, and cyclooctyl, which are C to Cs cycloalkyl group, alkylene group, alkenylene group, alkylidene group groups. and the like which are straight chain or branched chain 0087. The aforementioned cycloalkyl group may be monovalent or bivalent acyclic hydrocarbon groups; fused with benzene ring, naphthalene ring and the like, and cycloalkyl group, cycloalkenyl group, cycloalkanedienyl examples include, for example, 1-indanyl, 2-indanyl, 1.2.3, group, cycloalkyl-alkyl group, cycloalkylene group, and 4-tetrahydronaphthalen-1-yl, and 1.2.3,4-tetrahydronaph cycloalkenylene group, which are saturated or unsaturated thalen-2-yl. monovalent or bivalent alicyclic hydrocarbon groups. 0088. Examples of the cycloalkenyl group include, for 0080 Examples of the alkyl group include, for example, example, 2-cyclopropen-1-yl, 2-cyclobuten-1-yl, 2-cyclo methyl, ethyl, n-propyl, isopropyl. n-butyl, isobutyl, sec penten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-cy butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, 1-me clohexen-1-yl, 1-cyclobuten-1-yl, and 1-cyclopenten-1-yl, thylbutyl, neopentyl, 1,2-dimethylpropyl, 1-ethylpropyl. which are C to Ce cycloalkenyl groups. n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpenty1, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1.1- 0089. The aforementioned cycloalkenyl group may be dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2.3- fused with benzene ring, naphthalene ring and the like, and dimethylbutyl, 2-ethylbutyl, 1-ethylbutyl, 1-ethyl-1-methyl examples include, for example, 1-indanyl, 2-indanyl, 1.2.3, propyl, n-heptyl, n-octyl, n-nonyl, n-decyl. n-undecyl. 4-tetrahydronaphthalen-1-yl, 1.2.3,4-tetrahydronaphthalen n-dodecyl, n-tridecyl, n-tetradecyl, and n-pentadecyl, which 2-yl, 1-indenyl, and 2-indenyl. are C to Cs straight chain or branched chain alkyl groups. 0090. Examples of the cycloalkanedienyl group include, 0081 Examples of the alkenyl group include, for for example, 2.4-cyclopentadien-1-yl, 2.4-cyclohexanedien example, vinyl, prop-1-en-1-yl, allyl, isopropenyl, but-1-en 1-yl, and 2.5-cyclohexanedien-1-yl, which are Cs to C 1-yl, but-2-en-1-yl, but-3-en-1-yl, 2-methylprop-2-en-1-yl, cycloalkanedienyl groups. 1-methylprop-2-en-1-yl, pent-1-en-1-yl, pent-2-en-1-yl, 0091. The aforementioned cycloalkanedienyl group may pent-3-en-1-yl, pent-4-en-1-yl, 3-methylbut-2-en-1-yl, be fused with benzene ring, naphthalene ring and the like, 3-methylbut-3-en-1-yl, hex-1-en-1-yl, hex-2-en-1-yl, hex-3- and examples include, for example, 1-indenyl and 2-indenyl. US 2006/0122243 A1 Jun. 8, 2006

0092. Examples of the cycloalkyl-alkyl group include the 0099 Examples of the bridged cyclic hydrocarbon group groups in which one hydrogen atom of the alkyl group is include, for example, bicyclo2.1.0pentyl, bicyclo2.2.1 Substituted with a cycloalkyl group, and include, for heptyl, bicyclo2.2.1]octyl, and adamantyl. example, cyclopropylmethyl, 1-cyclopropylethyl 2-cyclo 0.100 Examples of the spiro cyclic hydrocarbon group propylethyl, 3-cyclopropylpropyl, 4-cyclopropylbutyl, 5-cy include, for example, spiro3.4loctyl, and spiro4.5deca-1, clopropylpentyl, 6-cyclopropylhexyl, cyclobutylmethyl, 6-dienyl. cyclopentylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclohexylpropyl, cyclohexylbutyl, 0101 Examples of the terpene hydrocarbon include, for cycloheptylmethyl, cyclooctylmethyl, and 6-cyclooctyl example, geranyl. neryl, linallyl, phytyl menthyl, and hexyl, which are C to C cycloalkyl-alkyl groups. bornyl. 0093 Examples of the cycloalkylene group include, for 0102) Examples of the halogenated alkyl group include example, cyclopropane-1,1-diyl, cyclopropane-1,2-diyl. the groups in which one hydrogen atom of the alkyl group cyclobutane-1,1-diyl, cyclobutane-1,2-diyl, cyclobutane-1, is Substituted with a halogen atom, and include, for example, 3-diyl, cyclopentane-1,1-diyl cyclopentane-1,2-diyl, cyclo fluoromethyl, difluoromethyl, trifluoromethyl, chlorom pentane-1,3-diyl, cyclohexane-1,1-diyl, cyclohexane-1,2- ethyl, dichloromethyl, trichloromethyl, bromomethyl, dibro diyl. cyclohexane-1,3-diyl. cyclohexane-1,4-diyl. momethyl, tribromomethyl, iodomethyl, diiodomethyl, tri cycloheptane-1,1-diyl cycloheptane-1,2-diyl, cyclooctane iodomethyl, 2.2.2-trifluoroethyl, pentafluoroethyl, 3,3,3- 1,1-diyl, and cyclooctane-1,2-diyl, which are C to Cs trifluoropropyl, heptafluoropropyl, heptafluoroisopropyl. cycloalkylene groups. nonafluorobutyl, and perfluorohexyl, which are C to C straight chain or branched chain halogenated alkyl groups 0094) Examples of the cycloalkenylene group include, substituted with 1 to 13 halogen atoms. for example, 2-cyclopropene-1,1-diyl 2-cyclobutene-1,1- diyl 2-cyclopentene-1,1-diyl 3-cyclopentene-1,1-diyl. 0.103 Examples of the heterocyclic group include, for 2-cyclohexene-1,1-diyl, 2-cyclohexene-1,2-diyl 2-cyclo example, a monocyclic or a fused polycyclic hetero aryl hexene-1,4-diyl, 3-cyclohexene-1,1-diyl, 1-cyclobutene-1, group which comprises at least one atom of 1 to 3 kinds of 2-diyl, 1-cyclopentene-1,2-diyl, and 1-cyclohexene-1,2- hetero atoms selected from oxygen atom, Sulfur atom, nitrogen atom and the like as ring-constituting atoms (ring diyl, which are C to Ce cycloalkenylene groups. forming atoms), and a monocyclic or a fused polycyclic 0.095 Examples of the aryl group include a monocyclic non-aromatic heterocyclic group which comprises at least or a fused polycyclic aromatic hydrocarbon group, and one atom of 1 to 3 kinds of hetero atoms selected from include, for example, phenyl, 1-naphthyl 2-naphthyl, oxygen atom, Sulfur atom, nitrogen atom and the like as anthryl, phenanthryl, and acenaphthylenyl, which are C to ring-constituting atoms (ring forming atoms). Caryl groups. 0.104 Examples of the monocyclic heteroaryl group 0096. The aforementioned aryl group may be fused with include, for example, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, the aforementioned C to Cs cycloalkyl group, C to C 1-pyrrolyl 2-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, cycloalkenyl group, Cs to Ce cycloalkanedienyl group or the 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thia like, and examples include, for example, 4-indanyl, 5-inda Zolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, nyl, 1.2.3,4-tetrahydronaphthalen-5-yl, 1,2,3,4-tetrahy 5-isothiazolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, dronaphthalen-6-yl, 3-acenaphthenyl, 4-acenaphthenyl, 5-imidazolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyra inden-4-yl, inden-5-yl, inden-6-yl, inden-7-yl 4-phenalenyl, Zolyl. (1.2.3-oxadiazol)-4-yl, (1,2,3-oxadiazol)-5-yl, (1,2,4- 5-phenalenyl, 6-phenalenyl, 7-phenalenyl, 8-phenalenyl, oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl, (1,2,5-oxadiazol)-3- and 9-phenalenyl. yl. (1,2,5-oxadiazol)-4-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4- oxadiazol)-5-yl, furazanyl. (1,2,3-thiadiaZol)-4-yl, (1,2,3- 0097 Examples of the arylene group include, for thiadiazol)-5-yl, (1,2,4-thiadiazol)-3-yl, (1,2,4-thiadiazol)- example, 1.2-phenylene, 1.3-phenylene, 1,4-phenylene, 5-yl, (1,2,5-thiadiazol)-3-yl, (1,2,5-thiadiazol)-4-yl, (1,3,4- naphthalene-1,2-diyl, naphthalene-1,3-diyl, naphthalene-1, thiadiazolyl)-2-yl, (1,3,4-thiadiazolyl)-5-yl, (1H-1,2,3- 4-diyl, naphthalene-1,5-diyl, naphthalene-1,6-diyl, naphtha triazol)-1-yl, (1H-1,2,3-triazol)-4-yl, (1H-1,2,3-triazol)-5- lene-1,7-diyl, naphthalene-1,8-diyl, naphthalene-2,3-diyl. yl. (2H-1,2,3-triazol)-2-yl. (2H-1,2,3-triazol)-4-yl, (1H-1.2. naphthalene-2,4-diyl, naphthalene-2,5-diyl, naphthalene-2, 4-triazol)-1-yl, (1H-1,2,4-triazol)-3-yl, (1H-1,2,4-triazol)-5- 6-diyl, naphthalene-2,7-diyl, naphthalene-2,8-diyl, and yl, (4H-1,2,4-triazol)-3-yl (4H-1,2,4-triazol)-4-yl, (1H anthracene-1,4-diyl, which are C to Carylene groups. tetrazol)-1-yl, (1H-tetrazol)-5-yl. (2H-tetrazol)-2-yl. (2H tetrazol)-5-yl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-pyridazinyl, 0.098 Examples of the aralkyl group include the groups 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, in which one hydrogen atom of the alkyl group is Substituted 2-pyrazinyl, (1,2,3-triazin)-4-yl. (1,2,3-triazin)-5-yl, (1,2,4- with an aryl group, and include, for example, benzyl, 1-naphthylmethyl 2-naphthylmethyl, anthracenylmethyl, triazin)-3-yl, (1,2,4-triazin)-5-yl, (1,2,4-triazin)-6-yl, (1,3,5- phenanthrenylmethyl, acenaphthylenylmethyl, diphenylm triazin)-2-yl, 1-azepinyl, 2-azepinyl, 3-azepinyl, 4-azepinyl, ethyl, 1-phenethyl 2-phenethyl, 1-(1-naphthyl)ethyl, 1-(2- (1,4-oxazepin)-2-yl, (1,4-oxazepin)-3-yl, (1,4-oxazepin)-5- naphthyl)ethyl, 2-(1-naphthyl)ethyl, 2-(2-naphthyl)ethyl, yl. (1,4-oxazepin)-6-yl, (1,4-oxazepin)-7-yl. (1,4-thiazepin)- 3-phenylpropyl, 3-(1-naphthyl)propyl, 3-(2-naphthyl)pro 2-yl, (1,4-thiazepin)-3-yl, (1,4-thiazepin)-5-yl, (1,4-thiaz pyl, 4-phenylbutyl, 4-(1-naphthyl)butyl, 4-(2-naphthyl)bu epin)-6-yl, and (1,4-thiazepin)-7-yl, which are 5 to tyl, 5-phenylpentyl, 5-(1-naphthyl)pentyl, 5-(2-naphthyl 7-membered monocyclic heteroaryl groups. )pentyl, 6-phenylhexyl, 6-(1-naphthyl)hexyl, and 6-(2- 0105 Examples of the fused polycyclic heteroaryl group naphthyl)hexyl, which are C7 to Caralkyl groups. include, for example, 2-benzofuranyl, 3-benzofuranyl.

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0109 The aforementioned cycloalkyl group, cycloalk dec-1-yn-1-yl)oxy, and (pentadec-14-yn-1-yl)oxy, which are enyl group, cycloalkanedienyl group, aryl group, cycloalky C. to Cs straight chain or branched chain alkynyl-oxy lene group, cycloalkenylene group, arylene group, bridged groups. cyclic hydrocarbon group, Spiro cyclic hydrocarbon group, 0114 Examples of the cycloalkyl-oxy group include, for and heterocyclic group are generically referred to as “cyclic example, cyclopropoxy, cyclobutoxy, cyclopentyloxy, group. Furthermore, among said cyclic groups, particularly, cyclohexyloxy, cycloheptyloxy, and cyclooctyloxy, which aryl group, arylene group, monocyclic heteroaryl group, and are C to Cs cycloalkyl-oxy groups. fused polycyclic heteroaryl group are generically referred to 0115 Examples of the cycloalkyl-alkyl-oxy group as 'aromatic ring group.” include, for example, cyclopropylmethoxy, 1-cyclopropy 0110. Examples of the hydrocarbon-oxy group include lethoxy, 2-cyclopropylethoxy, 3-cyclopropylpropoxy, 4-cy clopropylbutoxy, 5-cyclopropylpentyloxy, 6-cyclopropyl the groups in which a hydrogen atom of the hydroxy group hexyloxy, cyclobutylmethoxy, cyclopentylmethoxy, is Substituted with a hydrocarbon group, and examples of the cyclobutylmethoxy, cyclopentylmethoxy, cyclohexyl hydrocarbon include similar groups to the aforementioned methoxy, 2-cyclohexylethoxy, 3-cyclohexylpropoxy, 4-cy hydrocarbon groups. Examples of the hydrocarbon-oxy clohexylbutoxy, cycloheptylmethoxy, cyclooctylmethoxy, group include, for example, alkoxy group (alkyl-oxy group), and 6-cyclooctylhexyloxy, which are C to C cycloalkyl alkenyl-oxy group, alkynyl-oxy group, cycloalkyl-oxy alkyl-oxy groups. group, cycloalkyl-alkyl-oxy group and the like, which are aliphatic hydrocarbon-oxy groups: aryl-oxy group; aralkyl 0116 Examples of the aryl-oxy group include, for oxy group; and alkylene-dioxy group. example, phenoxy, 1-naphthyloxy, 2-naphthyloxy, anthry loxy, phenanthryloxy, and acenaphthylenyloxy, which are 0111 Examples of the alkoxy (alkyl-oxy group) include, C. to Caryl-oxy groups. for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-bu toxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, iso 0.117 Examples of the aralkyl-oxy group include, for pentyloxy, 2-methylbutoxy, 1-methylbutoxy, neopentyloxy, example, benzyloxy, 1-naphthylmethoxy, 2-naphthyl 1.2-dimethylpropoxy, 1-ethylpropoxy, n-hexyloxy, 4-meth methoxy, anthracenylmethoxy, phenanthrenylmethoxy, ylpentyloxy, 3-methylpentyloxy, 2-methylpentyloxy, 1-me acenaphthylenylmethoxy, diphenylmethoxy, 1-phenethy thylpentyloxy, 3.3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1- loxy, 2-phenethyloxy, 1-(1-naphthyl)ethoxy, 1-(2-naphthyl dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, )ethoxy, 2-(1-naphthyl)ethoxy, 2-(2-naphthyl)ethoxy, 3-phe 2,3-dimethylbutoxy, 2-ethylbutoxy, 1-ethylbutoxy, 1-ethyl nylpropoxy, 3-(1-naphthyl)propoxy, 3-(2-naphthyl)propoxy, 1-methylpropoxy, n-heptyloxy, n-octyloxy, n-nonyloxy, 4-phenylbutoxy, 4-(1-naphthyl)butoxy, 4-(2-naphthyl)bu toxy, 5-phenylpentyloxy, 5-(1-naphthyl)pentyloxy, 5-(2- n-decyloxy, n-undecyloxy, n-dodecyloxy, n-tridecyloxy, naphthyl)pentyloxy, 6-phenylhexyloxy, 6-(1-naphthyl)hexy n-tetradecyloxy, and n-pentadecyloxy, which are C to Cs loxy, and 6-(2-naphthyl)hexyloxy, which are C, to C. straight chain or branched chain alkoxy groups. aralkyl-oxy groups. 0112 Examples of the alkenyl-oxy group include, for 0118. Examples of the alkylenedioxy group include, for example, vinyloxy, (prop-1-en-1-yl)oxy, allyloxy, isoprope example, methylenedioxy, ethylenedioxy, 1-methylmethyl nyloxy, (but-1-en-1-yl)oxy, (but-2-en-1-yl)oxy, (but-3-en-1- enedioxy, and 1,1-dimethylmethylenedioxy. yl)oxy, (2-methylprop-2-en-1-yl)oxy, (1-methylprop-2-en 1-yl)oxy, (pent-1-en-1-yl)oxy, (pent-2-en-1-yl)oxy, (pent-3- 0119) Examples of the halogenated alkoxy group (halo en-1-yl)oxy, (pent-4-en-1-yl)oxy, (3-methylbut-2-en-1- genated alkyl-oxy group) include the groups in which a yl)oxy, (3-methylbut-3-en-1-yl)oxy, (hex-1-en-1-yl)oxy, hydrogen atom of the hydroxy group is Substituted with a (hex-2-en-1-yl)oxy, (hex-3-en-1-yl)oxy, (hex-4-en-1-yl)oxy, halogenated alkyl group, and include, for example, fluo (hex-5-en-1-yl)oxy, (4-methylpent-3-en-1-yl)oxy, (4-meth romethoxy, difluoromethoxy, chloromethoxy, bro ylpent-3-en-1-yl)oxy, (hept-1-en-1-yl)oxy, (hept-6-en-1- momethoxy, iodomethoxy, trifluoromethoxy, trichlo yl)oxy, (Oct-1-en-1-yl)oxy, (oct-7-en-1-yl)oxy, (non-1-en-1- romethoxy, 2.2.2-trifluoroethoxy, pentafluoroethoxy, 3,3,3- yl)oxy, (non-8-en-1-yl)oxy, (dec-1-en-1-yl)oxy, (dec-9-en trifluoropropoxy, heptafluoropropoxy, 1-yl)oxy, (undec-1-en-1-yl)oxy, (undec-10-en-1-yl)oxy, heptafluoroisopropoxy, nonafluorobutoxy, and perfluoro (dodec-1-en-1-yl)oxy, (dodec-11-en-1-yl)oxy, (tridec-1-en hexyloxy, which are C to C Straight chain or branched 1-yl)oxy, (tridec-12-en-1-yl)oxy, (tetradec-1-en-1-yl)oxy, chain halogenated alkoxy groups Substituted with 1 to 13 (tetradec-13-en-1-yl)oxy, (pentadec-1-en-1-yl)oxy, and halogen atoms. (pentadec-14-en-1-yl)oxy, which are C to Cs straight chain 0120 Examples of the heterocyclic-oxy group include or branched chain alkenyl-oxy groups. the groups in which a hydrogen atom of the hydroxy group 0113 Examples of the alkynyl-oxy group include, for is Substituted with a heterocyclic group, and examples of the example, ethynyloxy, (prop-1-yn-1-yl)oxy, (prop-2-yn-1- heterocyclic ring include similar groups to the aforemen yl)oxy, (but-1-yn-1-yl)oxy, (but-3-yn-1-yl)oxy, (1-methyl tioned heterocyclic groups. Examples of the heterocyclic prop-2-yn-1-yl)oxy, (pent-1-yn-1-yl)oxy, (pent-4-yn-1- oxy group include, for example, a monocyclic heteroaryl yl)oxy, (hex-1-yn-1-yl)oxy, (hex-5-yn-1-yl)oxy, (hept-1-yn oxy group, a fused polycyclic heteroaryl-oxy group, a 1-yl)oxy, (hept-6-yn-1-yl)oxy, (oct-1-yn-1-yl)oxy, (oct-7- monocyclic non-aromatic heterocyclic-oxy group, and a yn-1-yl)oxy, (non-1-yn-1-yl)oxy, (non-8-yn-1-yl)oxy, (dec fused polycyclic non-aromatic heterocyclic-oxy group. 1-yn-1-yl)oxy, (dec-9-yn-1-yl)oxy, (undec-1-yn-1-yl)oxy, 0121 Examples of the monocyclic heteroaryl-oxy group (undec-10-yn-1-yl)oxy, (dodec-1-yn-1-yl)oxy, (dodec-11 include, for example, 3-thienyloxy, (isoxazol-3-yl)oxy, yn-1-yl)oxy, (tridec-1-yn-1-yl)oxy, (tridec-12-yn-1-yl)oxy, (thiazol-4-yl)oxy, 2-pyridyloxy, 3-pyridyloxy, 4-pyridyloxy, (tetradec-1-yn-1-yl)oxy, (tetradec-13-yn-1-yl)oxy, (penta and (pyrimidin-4-yl)oxy.

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which are C to C Straight chain or branched chain halo genated alkyl-sulfanyl groups substituted with 1 to 13 halo -continued gen atoms. (c)-8A) 0134 Examples of the heterocyclic-sulfanyl group ---e. include the groups in which a hydrogen atom of the Sulfanyl S group is Substituted with a heterocyclic group, and examples (c)-9A) of the heterocyclic ring include similar groups to the afore ---e. mentioned heterocyclic groups. Examples of the heterocy O H clic-sulfanyl group include, for example, a monocyclic (c)-10A) heteroaryl-sulfanyl group, a fused polycyclic heteroaryl -C-N-Ra, Sulfanyl group, a monocyclic non-aromatic heterocyclic Sulfanyl group, and a fused polycyclic non-aromatic hetero (c)-11A) cyclic-Sulfanyl group. ---e. 0135 Examples of the monocyclic heteroaryl-sulfanyl S H group include, for example, (imidazol-2-yl)sulfanyl. (1,2,4- (c)-12A) triazol-2-yl)sulfanyl (pyridin-2-yl)sulfanyl. (pyridin-4-yl -C-N-Ra, )Sulfanyl, and (pyrimidin-2-yl)sulfanyl. 0136. Examples of the fused polycyclic heteroaryl-sulfa (c)-13A) nyl group include, for example, (benzimidazol-2-yl)sulfa -S-N-Ra, nyl, (quinolin-2-yl)sulfanyl, and (quinolin-4-yl)sulfanyl. | 0137 Examples of the monocyclic non-aromatic hetero O H cyclic-Sulfanyl groups include, for example, (3-pyrrolidinyl (c)-14A) )Sulfanyl, and (4-piperidinyl)sulfanyl. -S-N-Ra, 0138 Examples of the fused polycyclic non-aromatic | heterocyclic-sulfanyl group include, for example, (3-indoli O Rb1 nyl)sulfanyl, and (4-chromanyl)sulfanyl. (c)-15A)

0139 Examples of the acyl group include, for example, ---e.O H formyl group, glyoxyloyl group, thioformyl group, carbam (c)-16A) oyl group, thiocarbamoyl group, Sulfamoyl group, Sulfi -S-N-Ra, namoyl group, carboxy group, Sulfo group, phosphono group, and groups represented by the following formulas: (c)-17A)

-S-O-Ra, C-Ral (CO-1A) | O O (c)-18A) C-O-Ral (o)-2A) -i-o-e. O O (c)-19A) C-C-Ral (c)-3A) O-Ral || || -PO O O -C-C-O-Ra, (c)-4A) -R. || || O O (c)-20A) C-S-Ral (c)-5A) O | O --e. | C-Ral (c)-6A) O (c)-21A) S -S-Ra | O C-O-Ral (a)-7A)

S 0140 wherein R'' and R may be the same or different and represent a hydrocarbon group or a heterocyclic US 2006/0122243 A1 Jun. 8, 2006

group, or R'' and R' combine to each other, together with are referred to as referred to as “N-hydrocarbon-carbamoyl the nitrogen atom to which they bind, to form a cyclic group” whose examples include, for example, N-methylcar amino group. bamoyl group, and those groups in which R" is a hetero 0141. In the definition of the aforementioned acyl group, cyclic group are referred to as “N-heterocyclic ring-carbam among the groups represented by the formula (c)-1A), those oyl group.” groups in which R' is a hydrocarbon group are referred to 0151. Among the groups represented by the formula as “hydrocarbon-carbonyl group” whose examples include, for example, acetyl, propionyl, butyryl, isobutyryl, Valeryl, (c)-10A), those groups in which both R'' and R' are isovaleryl, pivaloyl, lauroyl, myristoryl, palmitoyl, acryloyl, hydrocarbon groups are referred to as propioloyl, methacryloyl, crotonoyl, isocrotonoyl cyclo 0152 “N,N-di(hydrocarbon)-carbamoyl group” whose hexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl, examples include, for example, N,N-dimethylcarbamoyl 1-naphthoyl 2-naphthoyl, and phenylacetyl, and those group, those groups in which both R" and R'' are groups in which R' is a heterocyclic group are referred to heterocyclic groups are referred to as “N,N-di(heterocy as "heterocyclic ring-carbonyl group' whose examples clic ring)-carbamoyl group.” those groups in which R" is include, for example, 2-thenoyl, 3-furoyl, nicotinoyl, and a hydrocarbon group and R is a heterocyclic group are isonicotinoyl. referred to as p0"N-hydrocarbon-N-heterocyclic ring 0142. Among the groups represented by the formula Substituted carbamoyl group.’ and those groups in which (co-2A), those groups in which R" is a hydrocarbon group R" and R' combine to each other, together with the are referred to as “hydrocarbon-oxy-carbonyl group” whose nitrogen atom to which they bind, to form a cyclic amino examples include, for example, methoxycarbonyl, ethoxy group are referred to as “cyclic amino-carbonyl group' carbonyl, phenoxycarbonyl, and benzyloxycarbonyl, and whose examples include, for example, morpholino-car those groups in which R" is a heterocyclic group are bonyl. referred to as "heterocyclic ring-oxy-carbonyl group' whose 0153. Among the groups represented by the formula examples include, for example, 3-pyridyloxycarbonyl. (a)-11A), those groups in which R" is a hydrocarbon group 0143 Among the groups represented by the formula are referred to as “N-hydrocarbon-thiocarbamoyl group.” (c)-3A), those groups in which R" is a hydrocarbon group and those groups in which R" is a heterocyclic group are are referred to as “hydrocarbon-carbonyl-carbonyl group' referred to as “N-heterocyclic ring-thiocarbamoyl group.” whose examples include, for example, pyruvoyl, and those 0154 Among the groups represented by the formula groups in which R" is a heterocyclic group are referred to (c)-12A), those groups in which both R" and R'' are as "heterocyclic ring-carbonyl-carbonyl group.” hydrocarbon groups are referred to as 0144. Among the groups represented by the formula O155 “N,N-di(hydrocarbon)-thiocarbamoyl group. s (c)-4A), those groups in which R" is a hydrocarbon group those groups in which both R" and R' are heterocyclic are referred to as “hydrocarbon-oxy-carbonyl-carbonyl groups are referred to as “N,N-di(heterocyclic ring)- group” whose examples include, for example, methoxalyl thiocarbamoyl group.” those groups in which R" is a and ethoxalyl groups, and those groups in which R" is a hydrocarbon group and R' is a heterocyclic group are heterocyclic group are referred to as "heterocyclic ring-oxy referred to as “N-hydrocarbon-N-heterocyclic ring-thio carbonyl-carbonyl group.” carbamoyl group.” and those groups in which R" and R' 0145 Among the groups represented by the formula combine to each other, together with the nitrogen atom to (c)-5A), those groups in which R" is a hydrocarbon group which they bind, to form a cyclic amino group are referred are referred to as “hydrocarbon-sulfanyl-carbonyl group.” to as "cyclic amino-thiocarbonyl group.” and those groups in which R" is a heterocyclic group are referred to as "heterocyclic ring-Sulfanyl-carbonyl group.” 0156 Among the groups represented by the formula (c)-13A), those groups in which R" is a hydrocarbon group 0146 Among the groups represented by the formula are referred to as “N-hydrocarbon-sulfamoyl group, and (co-6A), those groups in which R" is a hydrocarbon group those groups in which R" is a heterocyclic group are are referred to as “hydrocarbon-thiocarbonyl group, and those groups in which R" is a heterocyclic group are referred to as “N-heterocyclic ring-sulfamoyl group.” referred to as "heterocyclic ring-thiocarbonyl group.” 0157 Among the groups represented by the formula 0147 Among the groups represented by the formula (c)-14A), those groups in which both R'' and R' are (a)-7A), those groups in which R" is a hydrocarbon group hydrocarbon groups are referred to as are referred to as “hydrocarbon-oxy-thiocarbonyl group.” 0158 “N,N-di(hydrocarbon)-sulfamoyl group” whose and those groups in which R" is a heterocyclic group are examples include, for example, N,N-dimethylsulfamoyl referred to as "heterocyclic ring-oxy-thiocarbonyl group.” group, those groups in which both R" and R'' are 0148 Among the groups represented by the formula heterocyclic groups are referred to as “N,N-di(heterocy (c)-8A), those groups in which R" is a hydrocarbon group clic ring)-sulfamoyl group.” those groups in which R" is are referred to as “hydrocarbon-sulfanyl-thiocarbonyl a hydrocarbon group and R is a heterocyclic group are group.” and those groups in which R" is a heterocyclic referred to as “N-hydrocarbon-N-heterocyclic ring-sulfa group are referred to as moyl group,” and those groups in which R" and R' combine to each other, together with the nitrogen atom to 0149) "heterocyclic ring-Sulfanyl-thiocarbonyl group.” which they bind, to form a cyclic amino group are referred 0150. Among the groups represented by the formula to as “cyclic amino-Sulfonyl group” whose examples (c)-9A), those groups in which R" is a hydrocarbon group include, for example 1-pyrrolylsulfonyl. US 2006/0122243 A1 Jun. 8, 2006

0159 Among the groups represented by the formula group; an aralkyl-carbonyl group; a bridged cyclic hydro (c)-15A), those groups in which R" is a hydrocarbon group carbon-carbonyl group; a spirocyclic hydrocarbon-carbonyl are referred to as “N-hydrocarbon-sulfinamoyl group, and group; and a terpene family hydrocarbon-carbonyl group. In those groups in which R" is a heterocyclic group are the following, groups represented by the formulas (c)-2A) referred to as “N-heterocyclic ring-sulfinamoyl group.” through (c)-21A) are similar to those explained above. 0160 Among the groups represented by the formula 0169. Examples of the heterocyclic ring in the groups (c)-16A), those groups in which both R" and R'' are represented by the aforementioned formulas (co-1A) through hydrocarbon groups are referred to as (c)-21A) include similar groups to the aforementioned het erocyclic group. Examples of the heterocyclic ring-carbonyl 0161 “N,N-di(hydrocarbon)-sulfinamoyl group, those group represented by the formula (c)-1A) include, for groups in which both R" and R are heterocyclic groups example, a monocyclic heteroaryl-carbonyl group, a fused are referred to as “N,N-di(heterocyclic ring)-sulfinamoyl polycyclic heteroaryl-carbonyl group, a monocyclic non group.” those groups in which R" is a hydrocarbon group aromatic heterocyclic ring-carbonyl group, and a fused and R is a heterocyclic group are referred to as “N-hy polycyclic non-aromatic heterocyclic ring-carbonyl group. drocarbon-N-heterocyclic ring-Sulfinamoyl group.” and In the following, groups represented by the formulas (c)-2A) those groups in which R" and R' combine to each other, through (c)-21A) are similar to those explained above. together with the nitrogen atom to which they bind, to form a cyclic amino group are referred to as "cyclic 0170 Examples of the cyclic amino in the groups repre amino-Sulfinyl group.” sented by the aforementioned formulas (c)-10A) through (c)-16A) include similar groups to the aforementioned cyclic 0162 Among the groups represented by the formula amino group. (c)-17A), those groups in which R" is a hydrocarbon group 0171 In the present specification, when a certain func are referred to as “hydrocarbon-oxy-sulfonyl group, and tional group is defined as “which may be substituted,” the those groups in which R" is a heterocyclic group are definition means that the functional group may sometimes referred to as "heterocyclic ring-oxy-Sulfonyl group.” have one or more substituents at chemically substitutable 0163 Among the groups represented by the formula positions, unless otherwise specifically mentioned. Kind of (c)-18A), those groups in which R" is a hydrocarbon group Substituents, number of Substituents, and the position of are referred to as “hydrocarbon-oxy-sulfinyl group, and Substituents existing in the functional groups are not par those groups in which R" is a heterocyclic group are ticularly limited, and when two or more substituents exist, referred to as "heterocyclic ring-oxy-Sulfinyl group.” they may be the same or different. Examples of the sub stituent existing in the functional group include, for 0164. Among the groups represented by the formula example, halogen atoms, oxo group, thioxo group, nitro (c)-19A), those groups in which both R" and R' are group, nitroso group, cyano group, isocyano group, cyanato hydrocarbon groups are referred to as group, thiocyanato group, isocyanato group, isothiocyanato 0165 “O,O'-dichydrocarbon)-phosphono group, 99 those group, hydroxy group, Sulfanyl group, carboxy group, Sul groups in which both R" and R' are heterocyclic groups fanylcarbonyl group, oxalo group, methooxalo group, thio are referred to as “O,O'-dicheterocyclic ring)-phosphono carboxy group, dithiocarboxy group, carbamoyl group, thio group.” and those groups in which R" is a hydrocarbon carbamoyl group, Sulfo group, Sulfamoyl group, Sulfino group and R' is a heterocyclic group are referred to as group, Sulfinamoyl group, Sulfeno group, Sulfenamoyl “O-hydrocarbon-O'-heterocyclic ring-phosphono group.” group, phosphono group, hydroxyphosphonyl group, hydro carbon group, heterocyclic group, hydrocarbon-oxy group, 0166 Among the groups represented by the formula heterocyclic ring-oxy group, hydrocarbon-sulfanyl group, (c)-20A), those groups in which R" is a hydrocarbon group heterocyclic ring-sulfanyl group, acyl group, amino group, are referred to as “hydrocarbon-sulfonyl group” whose hydrazino group, hydrazono group, diazenyl group, ureido examples include, for example, methanesulfonyl and ben group, thioureido group, guanidino group, carbamoimidoyl Zenesulfonyl, and those groups in which R" is a heterocy group (amidino group), azido group, imino group. clic group are referred to as "heterocyclic ring-Sulfonyl hydroxyamino group, hydroxyimino group, aminooxy group.” group, diazo group, semicarbazino group, semicarbazono 0167 Among the groups represented by the formula group, allophanyl group, hydantoyl group, phosphano (c)-21A), those groups in which R" is a hydrocarbon group group, phosphoroso group, phospho group, boryl group. are referred to as “hydrocarbon-sulfinyl group” whose silyl group, Stannyl group, Selanyl group, oxido group and examples include, for example, methylsulfinyl and benze the like. nesulfinyl, and those groups in which R" is a heterocyclic 0.172. When two or more substituents exist according to group are referred to as "heterocyclic ring-Sulfinyl group.” the aforementioned definition of “which may be substi 0168 Examples of the hydrocarbon in the groups repre tuted,” said two or more Substituents may combine to each sented by the aforementioned formulas (c)-1A) through other, together with atom(s) to which they bind, to form a (c)-21A) include the similar groups to the aforementioned ring. For these cyclic groups, as ring-constituting atoms hydrocarbon group. Examples of the hydrocarbon-carbonyl (ring forming atoms), one to three kinds of one or more group represented by the formula (c)-1A) include, for hetero atoms selected from oxygen atom, Sulfur atom, example, an alkyl-carbonyl group, an alkenyl-carbonyl nitrogen atom and the like may be included, and one or more group, an alkynyl-carbonyl group, a cycloalkyl-carbonyl Substituents may exist on the ring. The ring may be mono group, a cycloalkenyl-carbonyl group, a cycloalkanedienyl cyclic or fused polycyclic, and aromatic or non-aromatic. carbonyl group, a cycloalkyl-alkyl-carbonyl group, which 0173 The above substituents according to the aforemen are aliphatic hydrocarbon-carbonyl groups; an aryl-carbonyl tioned definition of “which may be substituted may further US 2006/0122243 A1 Jun. 8, 2006

be substituted with the aforementioned substituents at the chemically substitutable positions on the substituent. Kind -continued of Substituents, number of Substituents, and positions of (c)-12B) substituents are not particularly limited, and when the sub -O-C-N-Ra2, stituents are substituted with two or more substituents, they ls may be the same or different. Examples of the substituent (c)-13B) include, for example, a halogenated alkyl-carbonyl group O whose examples include, for example, trifluoroacetyl, a -O-S-N-R4,a2 halogenated alkyl-sulfonyl group whose examples include, | for example, trifluoromethanesulfonyl, an acyl-oxy group, O H (c)-14B) an acyl-sulfanyl group, an N-hydrocarbon-amino group, an O N,N-di(hydrocarbon)-amino group, an N-heterocyclic ring amino group, an N-hydrocarbon-N-heterocyclic ring-amino -O-S-N-R4,a2 group, an acyl-amino group, and a di(acyl)-amino group. , Moreover, substitution on the aforementioned substituents (c)-15B) -O-S-N-Ra2, may be repeated multiple orders. | O H 0174 Examples of the acyl-oxy group include the groups (c)-16B) in which hydrogen atom of hydroxy group is Substituted -O-S-N-R, with acyl group, and include, for example, formyloxy group, glyoxyloyloxy group, thioformyloxy group, carbamoloxy , (c)-17B) group, thiocarbamoyloxy group, Sulfamoyloxy group, Sul O finamoloxy group, carboxyoxy group, Sulphooxy group, phosphonooxy group, and groups represented by the fol -O-S-O-Ra2, lowing formulas: O (c)-18B) -O-S-O-Ra, O-C-R2 (c)-1B) O | O O-Ra2 (c)-19B)

O-C-O-Ra2 (c)-2B) -O-PEO O -Rs. (c)-20B) O-C-C-Ra (c)-3B) O || || O O -O-S-Rap, a2 (c)-4B) -O-C-C-O-Ra4, O || || O O O-S-Ra2 (c)-21B)

O-C-S-Ra2 (c)-5B) O

O O-C-R2 (c)-6B) 0.175 wherein R* and R may be the same or different | and represent a hydrocarbon group or a heterocyclic S group, or RandR combine to each other, together with the nitrogen atom to which they bind, to form a cyclic O-C-O-Ra2 (a)-7B) amino group. S 0176). In the definition of the aforementioned acyl-oxy group, among the groups represented by the formula (c)-1B), O-C-S-Ra2 (c)-8B) those groups in which R" is a hydrocarbon group are S referred to as “hydrocarbon-carbonyl-oxy group' whose examples include, for example, acetoxy and benzoyloxy, O-C-N-Ra2 (c)-9B) and those groups in which R is a heterocyclic group are | referred to as "heterocyclic ring-carbonyl-oxy group.” O H 0.177 Among the groups represented by the formula O-C-N-Ra2 (c)-10B) (c)-2B), those groups in which R" is a hydrocarbon group I ls are referred to as “hydrocarbon-oxy-carbonyl-oxy group.” and those groups in which R is a heterocyclic group are O-C-N-Ra2 (c)-11B) referred to as "heterocyclic ring-oxy-carbonyl-oxy group.” S H 0.178 Among the groups represented by the formula (c)-3B), those groups in which R" is a hydrocarbon group US 2006/0122243 A1 Jun. 8, 2006 are referred to as “hydrocarbon-carbonyl-carbonyl-oxy are referred to as “N-hydrocarbon-thiocarbamoyl-oxy group.” and those groups in which R" is a heterocyclic group.” and those groups in which R is a heterocyclic group are referred to as group are referred to as 0179 "heterocyclic ring-carbonyl-carbonyl-oxy group.” 0194 “N-heterocyclic ring-thiocarbamoyl-oxy group.” 0180 Among the groups represented by the formula (c)-4B), those groups in which R' is a hydrocarbon group 0.195 Among the groups represented by the formula are referred to as “hydrocarbon-oxy-carbonyl-carbonyl-oxy (c)-12B), those groups in which both R" and R are group.” and those groups in which R" is a heterocyclic hydrocarbon groups are referred to as group are referred to as 0.196 “N,N-di(hydrocarbon)-thiocarbamoyl-oxy group.” those groups in which both R" and R are heterocyclic 0181 “heterocyclic ring-oxy-carbonyl-carbonyl-oxy groups are referred to as “N,N-di(heterocyclic ring)- group.” thiocarbamoyl-oxy group,” those groups in which R" is 0182 Among the groups represented by the formula a hydrocarbon group and R is a heterocyclic group are (c)-5B), those groups in which R" is a hydrocarbon group referred to as “N-hydrocarbon-N-heterocyclic ring-thio are referred to as “hydrocarbon-sulfanyl-carbonyl-oxy carbamoyl-oxy group.” and those groups in which R" and group.” and those groups where R is a heterocyclic group Rb2 combine to each other, together with the nitrogen are referred to as atom to which they bind, to form a cyclic amino group are referred to as “cyclicamino-thiocarbonyl-oxy group.” 0183) "heterocyclic ring-Sulfanyl-carbonyl-oxy group.” 0184 Among the groups represented by the formula 0.197 Among the groups represented by the formula (c)-6B), those groups in which R' is a hydrocarbon group (c)-13B), those groups in which R' is a hydrocarbon group are referred to as “hydrocarbon-thiocarbonyl-oxy group.” are referred to as “N-hydrocarbon-sulfamoyl-oxy group.” and those groups where R is a heterocyclic group are and those groups in which R is a heterocyclic group are referred to as "heterocyclic ring-thiocarbonyl-oxy group.” referred to as “N-heterocyclic ring-sulfamoyl-oxy group.” 0185. Among the groups represented by the formula 0198 Among the groups represented by the formula (a)-7B), those groups in which R" is a hydrocarbon group (co-14B), those groups in which both R" and R are are referred to as “hydrocarbon-oxy-thiocarbonyl-oxy hydrocarbon groups are referred to as group,” and those groups in which R is a heterocyclic 0199 “N,N-di(hydrocarbon)-sulfamoyl-oxy group. group are referred to as those groups in which both R" and R are heterocyclic groups are referred to as “N,N-di(heterocyclic ring)- 0186 “heterocyclic ring-oxy-thiocarbonyl-oxy group.” sulfamoyl-oxy group,” those groups in which R" is a 0187. Among the groups represented by the formula hydrocarbon group and R is a heterocyclic group are (c)-8B), those groups in which R' is a hydrocarbon group referred to as “N-hydrocarbon-N-heterocyclic ring-sulfa are referred to as “hydrocarbon-sulfanyl-thiocarbonyl-oxy moyl-oxy group.” and those groups in which R" and R' group.” and those groups wherein R is a heterocyclic combine to each other, together with the nitrogen atom to group are referred to as which they bind, to form a cyclic amino group are referred to as "cyclic amino-Sulfonyl-oxy group.” 0188 "heterocyclic ring-Sulfanyl-thiocarbonyl-oxy group.” 0200 Among the groups represented by the formula 0189 Among the groups represented by the formula (c)-15B), those groups in which R" is a hydrocarbon group (c)-9B), those groups in which R' is a hydrocarbon group are referred to as “N-hydrocarbon-sulfinamoyl-oxy group.” are referred to as “N-hydrocarbon-carbamoyl-oxy group.” and those groups where R is a heterocyclic group are and those groups in which R is a heterocyclic group are referred to as “N-heterocyclic ring-sulfinamoyl-oxy group.” referred to as “N-heterocyclic ring-carbamoyl-oxy group.” 0201 Among the groups represented by the formula 0190. Among the groups represented by the formula (c)-16B), those groups in which both R and R are (c)-10B), those groups in which both R'' and Rb2 are hydrocarbon groups are referred to as hydrocarbon groups are referred to as 0202 “N,N-di(hydrocarbon)-sulfinamoyl-oxy group.” 0191) “N,N-di(hydrocarbon)-carbamoyl-oxy group. those groups in which both R" and R are heterocyclic those groups in which both R" and R are heterocyclic groups are referred to as “N,N-di(heterocyclic ring)- groups are referred to as “N,N-di(heterocyclic ring)- Sulfinamoyl-oxy group,” those groups in which R is a carbamoyl-oxy group.” those groups in which R" is a hydrocarbon group and R is a heterocyclic group are hydrocarbon group and R is a heterocyclic group are referred to as “N-hydrocarbon-N-heterocyclic ring-sulfi referred to as “N-hydrocarbon-N-heterocyclic ring-car namoyl-oxy group,” and those groups in which R° and bamoyl-oxy group.” and those groups in which R'' and R combine to each other, together with the nitrogenatom Rb2 combine to each other, together with the nitrogen to which they bind, to form a cyclic amino group are atom to which they bind, to form a cyclicic amino group referred to as “cyclic amino-Sulfinyl-oxy group.” are referred to as 0203 Among the groups represented by the formula 0192 “cyclicamino-carbonyl-oxy group.” (c)-17B), those groups in which R" is a hydrocarbon group are referred to as “hydrocarbon-oxy-sulfonyl-oxy group.” 0193 Among the groups represented by the formula and those groups in which R is a heterocyclic group are (c)-11B), those groups in which R" is a hydrocarbon group referred to as "heterocyclic ring-oxy-Sulfonyl-oxy group.” US 2006/0122243 A1 Jun. 8, 2006

0204 Among the groups represented by the formula referred to as “substituted oxy group.” Moreover, these (c)-18B), those groups in which R' is a hydrocarbon group Substituted oxy group and hydroxy group are generically are referred to as “hydrocarbon-oxy-sulfinyl-oxy group.” referred to as “hydroxy group which may be substituted.” those groups in which R" is a heterocyclic group are referred to as "heterocyclic ring-oxy-Sulfinyl-oxy group.” 0213 Examples of the acyl-sulfanyl group include the 0205 Among the groups represented by the formula groups in which hydrogen atom of Sulfanyl group is Substi (co-19B), those groups in which both R" and R are tuted with acyl group, and include, for example, formylsul hydrocarbon groups are referred to as fanyl group, glyoxyloylsulfanyl group, thioformylsulfanyl group, carbamoyloxy group, thicarbamoyloxy group, Sulfa 0206 “O,O'-dichydrocarbon)-phosphono-oxy group.” moyloxy group, Sulfinamoyloxy group, carboxyoxy group, those groups in which both R" and R are heterocyclic Sulphooxy group, phosphonooxy group, and groups repre groups are referred to as "O.O'-dicheterocyclic ring)- phosphono-oxy group.” and those groups in which R" is sented by the following formulas: a hydrocarbon group and R is a heterocyclic group are referred to as “O-hydrocarbon substituted-O'-heterocyclic ring Substituted phophono-oxy group.” S-C-Ra3 (c)-1C)

0207 Among the groups represented by the formula O (c)-20B), those groups in which R" is a hydrocarbon group -2C are referred to as “hydrocarbon-sulfonyl-oxy group, and -S-C-O-Ra, (c)-2C) those groups in which R" is a heterocyclic group referred to O as "heterocyclic ring-Sulfonyl-oxy group.” -3C -S-C-C-Ra, (c)-3C) 0208 Among the groups represented by the formula || || (c)-21B), those groups in which R' is a hydrocarbon group O O are referred to as “hydrocarbon-sulfinyl-oxy group, and those groups in which R" is a heterocyclic group are -S-C-C-O-Ra, (c)-4C) referred to as "heterocyclic ring-Sulfinyl-oxy group.” || || O O 0209 Examples of the hydrocarbon in the groups repre -5C sented by the aforementioned formulas (c)-1B) through -S-C-S-Ras, (c)-5C) (c)-21B) include the similar groups to the aforementioned O hydrocarbon group. Examples of the hydrocarbon-carbonyl oxy group represented by the formula (c)-1B) include, for S-C-Ra3 (c)-6C) example, an alkyl-carbonyl-oxy group, an alkenyl-carbonyl S oxy group, an alkynyl-carbonyl-oxy group, a cycloalkyl -7C carbonyl-oxy group, a cycloalkenyl-carbonyl-oxy group, a -S-C-O-Ra, (a)-7C) cycloalkanedienyl-carbonyl-oxy group, and a cycloalkyl S alkyl-carbonyl-oxy group, which are aliphatic hydrocarbon -8C carbonyl-oxy groups; an aryl-carbonyl-oxy group; an -S-C-S-Ra, (c)-8C) aralkyl-carbonyl-oxy group; a bridged cyclic hydrocarbon | carbonyl-oxy group; a spirocyclic hydrocarbon-carbonyl S oxy group; and a terpene family hydrocarbon-carbonyl-oxy -9C -S-C-N-Ras, (c)-9C) group. In the following, groups represented by the formulas | (c)-2B) through (c)-21B) are similar to those explained O H above. S-C-N-R (c)-10C) 0210 Examples of the heterocyclic ring in the groups represented by the aforementioned formulas (c)-1B) through , (c)-21B) include similar groups to the aforementioned het erocyclic group. Examples of the heterocyclic ring-carbonyl S-C-N-R (c)-11C) group represented by the formula (c)-1B) include, for | example, a monocyclic heteroaryl-carbonyl group, a fused S H polycyclic heteroaryl-carbonyl group, a monocyclic non S-C-N-R (c)-12C) aromatic heterocyclic ring-carbonyl group, and a fused polycyclic non-aromatic heterocyclic ring-carbonyl group. (c)-13C) In the following, groups represented by the formulas (c)-2B) O through (c)-21B) are similar to those groups explained | above. -S-S-N-Ra, | 0211 Examples of the cyclic amino in the groups repre O H sented by the aforementioned formulas (c)-10B) through (c)-14C) (c)-16B) include similar groups to the aforementioned cyclic O amino group. -S-S-N-Ra, 0212. The aforementioned acyl-oxy group, hydrocarbon O Rb3 oxy group, and heterocyclic-oxy group are generically US 2006/0122243 A1 Jun. 8, 2006 16

0221) “hydrocarbon-oxy-carbonyl-carbonyl-sulfanyl -continued group.” and those groups in which R" is a heterocyclic group are referred to as "heterocyclic ring-oxy-carbonyl S-S-N-Ra (c)-15C) carbonyl-Sulfanyl group.” | O H 0222 Among the groups represented by the formula S-S-N-R (c)-16C) (c)-5C), those groups in which R" is a hydrocarbon group are referred to as “hydrocarbon-sulfanyl-carbonyl-sulfanyl , group.” and those groups in which R" is a heterocyclic (c)-17C) group are referred to as O 0223) “heterocyclic ring-Sulfanyl-carbonyl-Sulfanyl -S-S-O-Ra, group.” O 0224. Among the groups represented by the formula (c)-6C), those groups in which R" is a hydrocarbon group S-S-O-Ra (c)-18C) are referred to as “hydrocarbon-thiocarbonyl-sulfanyl O group.” and those groups in which R" is a heterocyclic O-Ra3 (c)-19C) group are referred to as 0225 "heterocyclic ring-thiocarbonyl-sulfanyl group.” -S-PEO 0226. Among the groups represented by the formula -R. (a)-7C), those groups in which R" is a hydrocarbon group (c)-20C) are referred to as “hydrocarbon-oxy-thiocarbonyl-sulfanyl O group.” and those groups in which R" is a heterocyclic -S-S-Ra, group are referred to as O 0227 “heterocyclic ring-oxy-thiocarbonyl-Sulfanyl group.” S-S-Ra3 (c)-21C) 0228. Among the groups represented by the formula O (co-8C), those groups in which R" is a hydrocarbon group are referred to as 0229) “hydrocarbon-sulfanyl-thiocarbonyl-sulfanyl 0214) wherein R and R may be the same or different group.” and those groups in which R" is a heterocyclic and represent a hydrocarbon group which may be substi group are referred to as "heterocyclic ring-Sulfanyl-thio tuted or a heterocyclic group which may be substituted, or carbonyl-Sulfanyl group.” R" and R combine to each other, together with the nitrogen atom to which they bind, to form a cyclic amino 0230. Among the groups represented by the formula group which may be substituted. (c)-9C), those groups in which R" is a hydrocarbon group are referred to as “N-hydrocarbon-carbamoyl-sulfanyl 0215. In the definition of the aforementioned acyl-sulfa group.” and those groups in which R" is a heterocyclic nyl group, among the groups represented by the formula group are referred to as (c)-1C), those groups in which R" is a hydrocarbon group 0231. “N-heterocyclic ring-carbamoyl-sulfanyl group.” are referred to as “hydrocarbon-carbonyl-sulfanyl group.” and those groups in which R" is a heterocyclic group are 0232 Among the groups represented by the formula referred to as "heterocyclic ring-carbonyl-sulfanyl group.” (c)-10C), those groups in which both R" and R are a hydrocarbon groups are referred to as 0216 Among the groups represented by the formula (c)-2C), those groups in which R" is a hydrocarbon group 0233 “N,N-di(hydrocarbon)-carbamoyl-sulfanyl group.” are referred to as “hydrocarbon-oxy-carbonyl-sulfanyl those groups in which both R" and Rare heterocyclic groups are referred to as “N,N-di(heterocyclic ring)- group.” and those groups in which R" is a heterocyclic carbamoyl-sulfanyl group,” those groups in which R" is group are referred to as a hydrocarbon group and R is a heterocyclic group are 0217 “heterocyclic ring-oxy-carbonyl-sulfanyl group.” referred to as “N-hydrocarbon-N-heterocyclic ring-car bamoyl-sulfanyl group.” and those groups in which R' 0218. Among the groups represented by the formula (c)-3C), those groups in which R" is a hydrocarbon group and R combine to each other, together with the nitrogen are referred to as “hydrocarbon-carbonyl-carbonyl-sulfanyl atom to which they bind, to form a cyclic amino group are group.” and those groups in which R" is a heterocyclic referred to as “cyclicamino-carbonyl-Sulfamoyl group.” group are referred to as 0234 Among the groups represented by the formula (c)-11C), those groups in which R" is a hydrocarbon group 0219) “heterocyclic ring-carbonyl-carbonyl-Sulfanyl are referred to as “N-hydrocarbon-thiocarbamoyl-sulfanyl group.” group.” and those groups in which R" is a heterocyclic 0220. Among the groups represented by the formula group are referred to as (co-4C), those groups in which R" is a hydrocarbon group 0235 “N-heterocyclic ring-thiocarbamoyl-Sulfanyl are referred to as group.” US 2006/0122243 A1 Jun. 8, 2006

0236 Among the groups represented by the formula 0248 Among the groups represented by the formula (c)-12C), those groups in which both R" and R are (c)-18C), those groups in which R" is a hydrocarbon group hydrocarbon groups are referred to as are referred to as “hydrocarbon-oxy-sulfinyl-sulfanyl 0237 “N,N-di(hydrocarbon)-thiocarbamoyl-sulfanyl group.” and those groups in which R" is a heterocyclic group,” those groups in which and R and R are group are referred to as heterocyclic groups are referred to as “N,N-di(heterocy 0249 "heterocyclic ring-oxy-Sulfinyl-Sulfanyl group.” clic ring)-thiocarbamoyl-sulfanyl group, those groups in 0250) Among the groups represented by the formula which R" is a hydrocarbon group and R is a heterocy (co-19C), those groups in which both R" and R are clic group are referred to as “N-hydrocarbon-N-hetero hydrocarbon groups are referred to as cyclic ring-thiocarbamoyl-sulfanyl group, and those groups in which R" and R combine to each other, 0251 “O,O'-dihydrocarbon)-phosphono-sulfanyl together with the nitrogen atom to which they bind, to group,” those groups in which both R" and R are form a cyclic amino group are referred to as “cycli heterocyclic groups are referred to as “O,O'-dicheterocy clic ring)-phosphono-sulfanyl group.’ and those groups in camino-thiocarbonyl-Sulfamoyl group.” which R" is a hydrocarbon group and R is a heterocy 0238 Among the groups represented by the formula clic group are referred to as “O-hydrocarbon-O'-hetero (c)-13C), those groups in which R" is a hydrocarbon group cyclic ring-phosphono-Sulfanyl group.” are referred to as “N-hydrocarbon-sulfamoyl-sulfanyl 0252 Among the groups represented by the formula group.” and those groups in which R" is a heterocyclic (c)-20C), those groups in which R" is a hydrocarbon group group are referred to as are referred to as “hydrocarbon-sulfonyl-sulfanyl group.” 0239) “N-heterocyclic ring-sulfamoyl-sulfanyl group.” and those groups in which R" is a heterocyclic group are 0240 Among the groups represented by the formula referred to as "heterocyclic ring-sulfonyl-sulfanyl group.” (c)-14C), those groups in which both R" and R are 0253 Among the groups represented by the formula hydrocarbon groups are referred to as (c)-21C), those groups in which R" is a hydrocarbon group 0241. “N,N-di(hydrocarbon)-sulfamoyl-sulfanyl group.” are referred to as “hydrocarbon-sulfinyl-sulfanyl group.” those groups in which both R" and Rare heterocyclic and those groups in which R" is a heterocyclic group are groups are referred to as “N,N-di(heterocyclic ring)- referred to as "heterocyclic ring-sulfinyl-sulfanyl group.” sulfamoyl-sulfinyl group,” those groups in which R" is a 0254 Examples of the hydrocarbon in the groups repre hydrocarbon group and R is a heterocyclic group are sented by the aforementioned formulas (c)-1C) through referred to as “N-hydrocarbon-N-heterocyclic ring-sulfa (c)-21 C) include similar groups to the aforementioned moyl-sulfanyl group.” and those groups in which R" and hydrocarbon group. Examples of the hydrocarbon-carbonyl R combine to each other, together with the nitrogen Sulfanyl group represented by the formula (c)-1C) include, atom to which they bind, to form a cyclic amino group are for example, an alkyl-carbonyl-sulfanyl group, an alkenyl referred to as “cyclicamino-Sulfonyl-Sulfanyl group.” carbonyl-sulfanyl group, an alkynyl-carbonyl-Sulfanyl group, a cycloalkyl-carbonyl-Sulfanyl group, a cycloalk 0242 Among the groups represented by the formula enyl-carbonyl-Sulfanyl group, a cycloalkanedienyl-carbo (c)-15C), those groups in which R" is a hydrocarbon group nyl-Sulfanyl group, a cycloalkyl-alkyl-carbonyl-Sulfanyl are referred to as “N-hydrocarbon-sulfinamoyl-sulfanyl group which are aliphatic hydrocarbon-carbonyl-Sulfanyl group.” and those groups in which R" is a heterocyclic groups; an aryl-carbonyl-sulfanyl group; an aralkyl-carbo group are referred to as nyl-Sulfanyl group; a bridged cyclic hydrocarbon-carbonyl 0243) “N-heterocyclic ring-sulfinamoyl-Sulfanyl group.” Sulfanyl group; a spiro cyclic hydrocarbon-carbonyl-Sulfa nyl group; and a terpene family hydrocarbon-carbonyl 0244 Among the groups represented by the formula Sulfanyl group. In the following, groups represented by the (c)-16C), those groups in which both R" and R are formulas (c)-2C) through (c)-21C) are similar to those hydrocarbon groups are referred to as explained above. 0245 “N,N-di(hydrocarbon)-sulfinamoyl-sulfanyl group,” those groups in which both R" and R are 0255 Examples of the heterocyclic ring in the groups heterocyclic groups are referred to as “N,N-di(heterocy represented by the aforementioned formulas (c)-1C) through clic ring)-sulfinamoyl-sulfanyl group.’ those groups in (c)-21 C) include similar groups to the aforementioned het which R" is a hydrocarbon group and R is a heterocy erocyclic group. Examples of the heterocyclic ring-carbo clic group are referred to as “N-hydrocarbon-N-hetero nyl-Sulfanyl group represented by the formula (c)-1C) cyclic ring-Sulfinamoyl-sulfanyl group.’ and those groups include, for example, a monocyclic heteroaryl-carbonyl in which RandR combine to each other, together with Sulfanyl group, a fused polycyclic heteroaryl-carbonyl-sul the nitrogen atom to which they bind, to form a cyclic fanyl group, a monocyclic non-aromatic heterocyclic ring amino group are referred to as “cyclicamino-sulfanyl carbonyl-sulfanyl group, and a fused polycyclic non Sulfanyl group.” aromatic heterocyclic ring-carbonyl-Sulfanyl group. In the following, groups represented by the formula (c)-2C) 0246 Among the groups represented by the formula through (c)-21 C) are similar to those groups explained (c)-17C), those groups in which R" is a hydrocarbon group above. are referred to as “hydrocarbon-oxy-sulfonyl-sulfanyl 0256 Examples of the cyclic amino in the groups repre group.” and those groups in which R" is a heterocyclic sented by the aforementioned formulas (c)-1C) through group are referred to as (c)-16C) include similar groups to the aforementioned cyclic 0247 "heterocyclic ring-oxy-sulfonyl-sulfanyl group.” amino group.

US 2006/0122243 A1 Jun. 8, 2006 example, N-methyl-N-(4-piperidinyl)amino, N-(4-chroma nyl)-N-methylamino, N-methyl-N-(3-thienyl)amino, N-me -continued thyl-N-(3-pyridyl)amino, N-methyl-N-(3-quinolyl)amino. ----e. (c)-15D) 0269. Examples of the acyl-amino group include the H. O. H. groups in which one hydrogen atom of the amino group is (c)-16D) Substituted with an acyl group, and include, for example, formylamino group, glyoxyloylamino group, thioformy ----e.H. O. Rb lamino group, carbamoylamino group, thiocarbamoylamino (c)-17D) group, Sulfamoylamino group, Sulfinamoylamino group, car boxyamino group, Sulphoamino group, phosphonoamino -N-S-O-Ra', group, and groups represented by the following formulas: | || H. O (c)-18D) N-C-Ra (c)-1D) --i-o-e H. O | || (c)-19D) H. O O-Ra -2D -N-C-O-Ra, (c)-2D) | || H. O ---0H Ö-Rb, -3D -N-C-C-Ra', (c)-3D) (c)-20D) | || || H. O. O. -N-S-Ra', | || -N-C-C-O-Ra, (c)-4D) H. O | || || H. O. O. (c)-21D) -5D -N-C-S-Ra', (c)-5D) ---" | || H. O H. O N-C-Ra (c)-6D) | || 0270 wherein R and R may be the same or different H S and represent a hydrocarbon group which may be substi -7D tuted or a heterocyclic group which may be substituted, or -N-C-O-Ra', (a)-7D) R" and R combine to each other, together with the | || H S nitrogen atom to which they bind, to form a cyclic amino -8D group which may be substituted. -N-C-S-Ra, (c)-8D) | || 0271 In the definition of the aforementioned acyl-amino H S group, among the groups represented by the formula (c)-1D), -9D -N-C-N-Ra', (c)-9D) those groups in which R" is a hydrocarbon group are | || | referred to as “hydrocarbon-carbonyl-amino group.’ and H. O. H. those groups in which R" is a heterocyclic group are referred to as "heterocyclic ring-carbonyl-amino group.” N-C-N-R (c)-10D) | || | 0272 Among the groups represented by the formula O Rb4 (c)-2D), those groups in which R" is a hydrocarbon group N-C-N-R (c)-11D) are referred to as “hydrocarbon-oxy-carbonyl-amino | || | group,” and those groups in which R" is a heterocyclic H S H group are referred to as "heterocyclic ring-oxy-carbonyl N-C-N-R (c)-12D) amino group.”

H S R 0273 Among the groups represented by the formula (c)-13D) (c)-3D), those groups in which R" is a hydrocarbon group O | are referred to as “hydrocarbon-carbonyl-carbonyl-amino -N-S-N-R, group,” and those groups in which R" is a heterocyclic | || | group are referred to as H. O. H. (c)-14D) 0274) "heterocyclic ring-carbonyl-carbonyl-amino O group.” -N-S-N-R, 0275 Among the groups represented by the formula H. O. Rb (c)-4D), those groups in which R" is a hydrocarbon group are referred to as US 2006/0122243 A1 Jun. 8, 2006 20

0276 “hydrocarbon-oxy-carbonyl-carbonyl-amino 0290 “N,N-di(hydrocarbon)-thiocarbamoyl-amino group.” and those groups in which R" is a heterocyclic group,” those groups in which both R" and R are group are referred to as "heterocyclic ring-oxy-carbonyl heterocyclic groups are referred to as “N,N-di(heterocy carbonyl-amino group.” clic ring)-thiocarbamoyl-amino group.’ those groups in which R" is a hydrocarbon group and R is a heterocy 0277 Among the groups represented by the formula clic group are referred to as “N-hydrocarbon-N-hetero (c)-5D), those groups in which R" is a hydrocarbon group cyclic ring-thiocarbamoyl-amino group.’ and those are referred to as “hydrocarbon-sulfanyl-carbonyl-amino groups in which R" and R combine to each other, group.” and those groups in which R" is a heterocyclic together with the nitrogen atom to which they bind, to group are referred to as form a cyclic amino group are referred to as “cyclic 0278 "heterocyclic ring-Sulfanyl-carbonyl-amino amino-thiocarbonyl-amino group.” group.” 0291 Among the groups represented by the formula 0279 Among the groups represented by the formula (c)-13D), those groups in which R" is a hydrocarbon group (c)-6D), those groups in which R" is a hydrocarbon group are referred to as “N-hydrocarbon-sulfamoyl-amino group.” are referred to as “hydrocarbon-thiocarbonyl-amino group.” and those groups in which R" is a heterocyclic group are and those groups in which R" is a heterocyclic group are referred to as “N-heterocyclic ring-Sulfamoyl-amino group.” referred to as "heterocyclic ring-thiocarbonyl-amino group.” 0292 Among the groups represented by the formula 0280 Among the groups represented by the formula (co-14D), those groups in which both R'' and R are (a)-7D), those groups in which R" is a hydrocarbon group hydrocarbon groups are referred to as are referred to as “hydrocarbon-oxy-thiocarbonyl-amino 0293 “di(hydrocarbon)-sulfamoyl-amino group, those group,” and those groups in which R" is a heterocyclic groups in which both R" and Rare heterocyclic groups group are referred to as are referred to as “N,N-di(heterocyclic ring)-sulfamoyl amino group.” those groups in which R" is a hydrocarbon 0281) “heterocyclic ring-oxy-thiocarbonyl-amino group and R is a heterocyclic group are referred to as group.” “N-hydrocarbon-N-heterocyclic ring-sulfamoyl-amino 0282 Among the groups represented by the formula group.” and those groups in which R" and R' combine (c)-8D), those groups in which R" is a hydrocarbon group to each other, together with the nitrogen atom to which are referred to as they bind, to form a cyclic amino group are referred to as 0283 “hydrocarbon-sulfanyl-thiocarbonyl-amino “cyclic amino-Sulfonyl-amino group.” group,” and those groups in which R" is a heterocyclic 0294 Among the groups represented by the formula group are referred to as "heterocyclic ring-Sulfanyl-thio (c)-15D), those groups in which R" is a hydrocarbon group carbonyl-amino group.” are referred to as “N-hydrocarbon-sulfinamoyl-amino 0284 Among the groups represented by the formula group.” and those groups in which R" is a heterocyclic (c)-9D), those groups in which R" is a hydrocarbon group group are referred to as are referred to as “N-hydrocarbon-carbamoyl group, and 0295) “N-heterocyclic ring-sulfinamoyl-amino group.” those groups in which R" is a heterocyclic group are 0296 Among the groups represented by the formula referred to as “N-heterocyclic ring-carbamoyl-amino (c)-16D), those groups in which both R" and R are group.” hydrocarbon groups are referred to as 0285 Among the groups represented by the formula 0297 “N,N-di(hydrocarbon)-sulfinamoyl-amino group.” (co-10D), those groups in which both R'' and R are those groups in which both R" and Rare heterocyclic groups are referred to as “N,N-di(heterocyclic ring)- hydrocarbon groups are referred to as sulfinamoyl-amino group.” groups in which R" is a 0286 “N,N-di(hydrocarbon)-carbamoyl-amino group.” hydrocarbon group and R is a heterocyclic group are those groups in which both R'' and R are heterocyclic referred to as “N-hydrocarbon-N-heterocyclic ring-sulfi groups are referred to as “N,N-di(heterocyclic ring)- namoyl-amino group.” and those groups in which R" and carbamoyl-amino group,” those groups in which R" is a R* combine to each other, together with the nitrogen hydrocarbon group and R is a heterocyclic group are atom to which they bind, to form a cyclic amino group are referred to as “N-hydrocarbon-N-heterocyclic ring-car referred to as “cyclic amino-Sulfinyl-amino group.” bamoyl-amino group.” and those groups in which R'' and 0298 Among the groups represented by the formula R" combine to each other, together with the nitrogen (c)-17D), those groups in which R" is a hydrocarbon group atom to which they bind, to form a cyclic amino group are are referred to as “hydrocarbon-oxy-Sulfonyl-amino group.” referred to as “cyclic amino-carbonyl-amino group.” and those groups in which R" is a heterocyclic group are 0287 Among the groups represented by the formula referred to as "heterocyclic ring-oxy-Sulfoyl-amino group.” (c)-11D), those groups in which R" is a hydrocarbon group 0299 Among the groups represented by the formula are referred to as “N-hydrocarbon-thiocarbamoyl-amino (c)-18D), those groups in which R" is a hydrocarbon group group.” and those groups in which R" is a heterocyclic ring are referred to as “hydrocarbon-oxy-Sulfinyl-amino group.” group are referred to as and those groups in which R" is a heterocyclic group are 0288 “N-heterocyclic-thiocarbamoyl-amino group.” referred to as "heterocyclic ring-oxy-Sulfinyl-amino group.” 0289 Among the groups represented by the formula 0300 Among the groups represented by the formula (c)-12D), those groups in which both R" and R are (c)-19D), those groups in which both R" and R are hydrocarbon groups are referred to as hydrocarbon groups are referred to as US 2006/0122243 A1 Jun. 8, 2006

0301 “O,O'-dichydrocarbon)-phosphono-amino group.” those groups in which both R'' and R are heterocyclic groups are referred to as "O.O'-dicheterocyclic ring)- (c)-1E) phosphono-amino group.” and those groups in which R' is a hydrocarbon group and R is a heterocyclic group are referred to as “O-hydrocarbon-O'-heterocyclic ring phosphono-amino group.” (c)-2E) 0302 Among the groups represented by the formula (c)-20D), those groups in which R" is a hydrocarbon group are referred to as “hydrocarbon-sulfonyl-amino group.’ and (c)-3E) those groups in which R" is a heterocyclic group are referred to as "heterocyclic ring-Sulfonyl-amino group.” -N || || ) O O 22 0303 Among the groups represented by the formula (c)-4E) (c)-21D), those groups in which R" is a hydrocarbon group -N-HC-C-O-Ras are referred to as “hydrocarbon-sulfinyl-amino group.” and those groups in which R" is a heterocyclic group are ) referred to as "heterocyclic ring-Sulfinyl-amino group.” (c)-5E) 0304 Examples of the hydrocarbon in the groups repre sented by the aforementioned formulas (c)-1D) through (c)-21D) include the similar groups to the aforementioned hydrocarbon group. Examples of the hydrocarbon-carbonyl amino groups represented by the formula (c)-1D) include, for example, an alkyl-carbonyl-amino group, an alkenyl carbonyl-amino group, an alkynyl-carbonyl-amino group, a cycloalkyl-carbonyl-amino group, a cycloalkenyl-carbonyl (a)-7E) amino group, a cycloalkanedienyl-carbonyl-amino group, a cycloalkyl-alkyl-carbonyl-amino group which are aliphatic hydrocarbon-carbonyl-amino groups; an aryl-carbonyl amino group; an aralkyl-carbonyl-amino group; a bridged cyclic hydrocarbon-carbonyl-amino group; a spiro cyclic hydrocarbon-carbonyl-amino group; and a terpene family hydrocarbon-carbonyl-amino group. In the following, groups represented by the formulas (co-2D) through (co-21D) are similar to those explained above. 0305 Examples of the heterocyclic ring in the groups represented by the aforementioned formulas (c)-1D) through (c)-10E) (c)-21D) include similar groups to the aforementioned het erocyclic group. Examples of the heterocyclic ring-carbo nyl-amino group represented by the formula (c)-1D) include, for example, a monocyclic heteroaryl-carbonyl-amino (c)-11E) group, a fused polycyclic heteroaryl-carbonyl-amino group, a monocyclic non-aromatic heterocyclic-carbonyl-amino group, and a fused polycyclic non-aromatic heterocyclic carbonyl-amino group. In the following, groups represented (c)-12E) by the formulas (co-2D) through (c)-21D) are similar to those groups explained above. 0306 Examples of the cyclic amino in the groups repre (c)-13E) sented by the aforementioned formulas (co-10D) through (c)-16D) include similar groups to the aforementioned cyclic amino group. 0307 Examples of the di(acyl)-amino group include the groups in which two hydrogen atoms of amino group are (c)-14E) substituted with acyl groups in the definitions of the afore O mentioned substituents according to “which may be substi -N--S-N-Ras tuted.” Examples include, for example, di(formyl)-amino group, di(glyoxyloyl)-amino group, di(thioformyl)-amino I ls group, di(carbamoyl)-amino group, di(thiocarbamoyl)- (c)-15E) amino group, di(Sulfamoyl)-amino group, di(Sulfinamoyl)- amino group, di(carboxy)-amino group, di(Sulfo)-amino group, di(phosphono)-amino group, and groups represented by the following formulas: US 2006/0122243 A1 Jun. 8, 2006 22

group are referred to as “bis(heterocyclic ring-oxy-carbo -continued nyl-carbonyl)-amino group.” (c)-16E) 0315 Among the groups represented by the formula (c)-5E), those groups in which R" is a hydrocarbon group - (-r)O Rb5 2: are referred to as (c)-17E) 0316 “bis(hydrocarbon-sulfanyl-carbonyl)-amino O group.” and those groups in which R" is a heterocyclic -N-HS-O-Ras group are referred to as “bis(heterocyclic ring-sulfanyl carbonyl)-amino group.” O 22 0317. Among the groups represented by the formula (c)-18E) -N-HS-N-Ras (c)-6E), those groups in which R" is a hydrocarbon group | are referred to as “bis(hydrocarbon-thiocarbonyl)-amino O 22 group.” and those groups in which R" is a heterocyclic (c)-19E) group are referred to as O-Ras 0318 “bis(heterocyclic ring-thiocarbonyl)-amino group.” -N =o 0319 Among the groups represented by the formula o-R/, (a)-7E), those groups in which R" is a hydrocarbon group (c)-20E) are referred to as O 0320 “bis(hydrocarbon-oxy-thiocarbonyl)-amino -N-HS-Ras group.” and those groups in which R" is a heterocyclic group are referred to as “bis(heterocyclic ring-oxy-thio O 22 carbonyl)-amino group. (c)-21E) 0321. Among the groups represented by the formula -N (co-8E), those groups in which R" is a hydrocarbon group are referred to as 0322 “bis(hydrocarbon-sulfanyl-thiocarbonyl)-amino group.” and those groups in which R" is a heterocyclic 0308 wherein R* and R may be the same or different group are referred to as “bis(heterocyclic ring-sulfanyl and represent hydrogen atom, a hydrocarbon group which thiocarbonyl)-amino group.” may be substituted or a heterocyclic group which may be 0323 Among the groups represented by the formula substituted, or R and R combine to each other, (c)-9E), those groups in which R" is a hydrocarbon group together with the nitrogen atom to which they bind, to are referred to as “bis(N-hydrocarbon-carbamoyl)-amino form a cyclic amino group which may be substituted. group.” and those groups in which R" is a heterocyclic 0309. In the definition of aforementioned di(acyl)-amino group are referred to as group, among the groups represented by the formula (c)-1E), those groups in which R" is a hydrocarbon group are 0324) “bis(N-heterocyclic ring-carbamoyl)-amino referred to as “bis(hydrocarbon-carbonyl)-amino group.” group.” and those groups in which R" is a heterocyclic group are 0325 Among the groups represented by the formula referred to as “bis(heterocyclic ring-carbonyl)-amino group. (c)-10E), those groups in which both R" and Rb5 are 0310. Among the groups represented by the formula hydrocarbon groups are referred to as (c)-2E), those groups in which R" is a hydrocarbon group 0326 “bisN,N-di(hydrocarbon)-carbamoyl-amino are referred to as “bis(hydrocarbon-oxy-carbonyl)-amino group,” those groups in which both R" and R are group.” and those groups in which R" is a heterocyclic heterocyclic groups are referred to as “bisN,N-di(hetero group are referred to as “bis(heterocyclic ring-oxy-carbo cyclic ring)-carbamoyl-amino group.’ groups in which nyl)-amino group.” R is a hydrocarbon group and R is a heterocyclic group are referred to as “bis(N-hydrocarbon-N-heterocyclic 0311. Among the groups represented by the formula ring-carbamoyl)-amino group.’ and those groups in (c)-3E), those groups in which R" is a hydrocarbon group which R" and R combine to each other, together with are referred to as the nitrogen atom to which they bind, to form a cyclic 0312 “bis(hydrocarbon-carbonyl-carbonyl)-amino amino groups are referred to as “bis(cyclic amino-carbo group.” and those groups in which R" is a heterocyclic nyl)amino group.” group are referred to as "bis(heterocyclic ring-carbonyl 0327. Among the groups represented by the formula carbonyl)-amino group. (c)-11E), those groups in which R" is a hydrocarbon group 0313 Among the groups represented by the formula are referred to as (co-4E), those groups in which R" is a hydrocarbon group 0328 “bis(N-hydrocarbon-thiocarbamoyl)-amino are referred to as group.” and those groups in which R" is a heterocyclic 0314 “bis(hydrocarbon-oxy-carbonyl-carbonyl)-amino group are referred to as “bis(N-heterocyclic ring-thiocar group.” and those groups in which R" is a heterocyclic bamoyl)-amino group.” US 2006/0122243 A1 Jun. 8, 2006

0329. Among the groups represented by the formula are referred to as “bis(hydrocarbon-oxy-sulfonyl)-amino (c)-12E), those groups in which both R" and R are group.” and those groups in which R" is a heterocyclic hydrocarbon groups are referred to as group are referred to as 0330 "bisN,N-di(hydrocarbon)-thiocarbamoyl-amino 0340 “bis(heterocyclic ring-oxy-Sulfonyl)-amino group,” those groups in which both R" and R are group.” heterocyclic groups are referred to as “bis N,N-di(hetero 0341 Among the groups represented by the formula cyclic ring)-thiocarbamoyl-amino group, those groups (c)-18E), those groups in which R" is a hydrocarbon group in which R" is a hydrocarbon group and R is a hetero are referred to as “bis(hydrocarbon-oxy-sulfinyl)-amino cyclic group are referred to as “bis(N-hydrocarbon-N- heterocyclic ring-thiocarbamoyl)-amino group.’ and group.” and those groups in which R" is a heterocyclic those groups in which R" and R combine to each other, group are referred to as together with the nitrogen atom to which they bind, to 0342 “bis(heterocyclic ring-oxy-Sulfinyl)-amino group. s form a cyclic amino group are referred to as “bis(cyclic 0343 Among the groups represented by the formula amino-thiocarbonyl)-amino group.” (co-19E), those groups in which both R" and R are 0331 Among the groups represented by the formula hydrocarbon groups are referred to as (c)-13E), those groups in which R" is a hydrocarbon group 0344) “bisO.O'-dichydrocarbon)-phosphono-amino are referred to as “bis(N-hydrocarbon-sulfamoyl)-amino group,” those groups in which both R" and R are group.” and those groups in which R" is a heterocyclic heterocyclic groups are referred to as “bisO,O'-di(het group are referred to as erocyclic ring)-phosphono-amino group,” and those groups in which R" is a hydrocarbon group and R is a 0332 “bis(N-heterocyclic ring-Sulfamoyl)-amino heterocyclic group are referred to as “bis(O-hydrocarbon group.” O'-heterocyclic ring-phosphono)-amino group.” 0333 Among the groups represented by the formula 0345 Among the groups represented by the formula (c)-14E), those groups in which both R" and R are (c)-20E), those groups in which R" is a hydrocarbon group hydrocarbon groups are referred to as are referred to as “bis(hydrocarbon-sulfonyl)-amino group.” 0334 “bisN,N-di(hydrocarbon)-sulfamoyl-amino and those groups in which R" is a heterocyclic group are group.” those groups in which both R" and R are referred to as heterocyclic groups are referred to as “bis N,N-di(hetero “bis(heterocyclic ring-Sulfonyl)-amino group.” cyclic ring)-sulfamoyl-amino group, those groups in 0346) which R" is a hydrocarbon group and R is a heterocy 0347 Among the groups represented by the formula clic group are referred to as “bis(N-hydrocarbon-N-het (c)-21E), those groups in which R" is a hydrocarbon group erocyclic ring-Sulfamoyl)-amino group.’ and those are referred to as “bis(hydrocarbon-sulfinyl)-amino group.” groups in which R" and R combine to each other, and those groups in which R" is a heterocyclic group are together with the nitrogen atom to which they bind, to referred to as form a cyclic amino group are referred to as “bis(cyclic “bis(heterocyclic ring-Sulfinyl)-amino group.” amino-Sulfonyl)amino group.” 0348 0349 Examples of the hydrocarbon in the groups repre 0335 Among the groups represented by the formula sented by the aforementioned formulas (c)-1E) through (c)-15E), those groups in which R" is a hydrocarbon group (c)-21E) include the similar groups to the aforementioned are referred to as “bis(N-hydrocarbon-sulfinamoyl)-amino hydrocarbon group. Examples of the bis(hydrocarbon-car group.” and those groups in which R" is a heterocyclic bonyl)-amino groups represented by the formula (c)-1E) group are referred to as include, for example, a bis(alkyl-carbonyl)-amino group, a bis(alkenyl-carbonyl)-amino group, a bis(alkynyl-carbo 0336 “bis(N-heterocyclic ring-Sulfinamoyl)-amino nyl)-amino group, a bis(cycloalkyl-carbonyl)-amino group, group.” a bis(cycloalkenyl-carbonyl)-amino group, a bis(cycloal 0337 Among the groups represented by the formula kanedienyl-carbonyl)-amino group, a bis(cycloalkyl-alkyl (c)-16E), those groups in which R" and Rare hydrocarbon carbonyl)-amino group which are bis(aliphatic hydrocarbon groups are referred to as carbonyl)-amino groups; a bis(aryl-carbonyl)-amino group; a bis(aralkyl-carbonyl)-amino group; a bis(bridged cyclic 0338 “bisN,N-di(hydrocarbon)-sulfinamoyl-amino hydrocarbon-carbonyl)-amino group; a bis(spiro cyclic group,” those groups in which R" and Rare heterocy hydrocarbon-carbonyl)-amino group; and a bis(terpene fam clic groups are referred to as “bisN,N-di(heterocyclic ily hydrocarbon-carbonyl)-amino group. In the following, ring)-sulfinamoyl-amino group, those groups in which groups represented by the formulas (c)-2E) through (c)-21E) R is a hydrocarbon group and R is a heterocyclic group are similar to those explained above. are referred to as “bis(N-hydrocarbon-N-heterocyclic ring-Sulfinamoyl)-amino group, and those groups in 0350 Examples of the heterocyclic ring in the groups which R" and R combine to each other, together with represented by the aforementioned formulas (c)-1E) through the nitrogen atom to which they bind, to form a cyclic (c)-21E) include similar groups to the aforementioned het amino group are referred to as “bis(cyclic amino-sulfiny erocyclic group. Examples of the bis(heterocyclic ring l)amino group.” carbonyl)-amino group represented by the formula (c)-1E) include, for example, a bis(monocyclic heteroaryl-carbo 0339 Among the groups represented by the formula nyl)-amino group, a bis(fused polycyclic heteroaryl-carbo (c)-17E), those groups in which R" is a hydrocarbon group nyl)-amino group, a bis(monocyclic non-aromatic heterocy US 2006/0122243 A1 Jun. 8, 2006 24 clic-carbonyl)-amino group, and a bis(fused polycyclic non aromatic heterocyclic-carbonyl)-amino group. In the -continued following, groups represented by the formulas (c)-2E) through (c)-21E) are similar to those groups explained --- -CEC- --- above. H. H. H 0351 Examples of the cyclic amino in the groups repre -- - NEN- --- sented by the aforementioned formulas (c)-10E) through H O (c)-16E) include similar groups to the aforementioned cyclic amino group. 0352. The aforementioned acyl-amino group and di(a- 0359 When 2 or more divalent groups combine, each cyl)-amino group are generically referred to as “acyl Sub group may be the same or different. stituted amino group.” Furthermore, the aforementioned N-hydrocarbon-amino group, N,N-di(hydrocarbon)-amino 0360 The aforementioned “connecting group wherein group, N-heterocyclic-amino group, N-hydrocarbon-N-het the number of atoms of the main chain is 2 to 5,” is erocyclic-amino group, cyclic amino group, acyl-amino preferably a group selected from the following “connecting group, and di(acyl)-amino group are generically referred to group C. aS 0361 Connecting Group C the Following Formulas: 0353) “substituted amino group.” 0354) In the following, compounds represented by the aforementioned general formula (I) are explained in details. | -C-N-, -C-N-C-, 0355 “Connecting group whose number of atoms of | main chain is 2 to 5’ in the definition of X means connecting O H O H. H. groups wherein 2 to 5 atoms in a main chain link together between rings Z and E. The aforementioned “number of -C-N-C-C-, -C-C-C-, atoms of the main chain' is counted so as to minimize the | | | | | number of connecting atoms existing between the rings Z O H. H. H. O H. H. and E. regardless of the presence or absence of hetero H H O atom(s). For example, the number of atoms of 1.2-cyclo -C-CEC-, -CEC-, -S-N- pentylene is counted as 2, the number of atoms of 1,3- | | cyclopentylene is counted as 3, the number of atoms of O H H O H O H 1,4-phenylene is counted as 4, and the number of atoms of | 2,6-pyridine-diyl is counted as 3. -N-C-, -N-S-, -C-N-, 0356. The aforementioned “connecting group whose | || | || number of atoms of main chain is 2 to 5’ is formed by one H. O H. O H. H. functional group selected from the following group of | -C-N-N=C-, -C-N-C-C-N-, divalent group C-1, or formed by combining 2 to 4 functional | | | | || | groups of 1 to 4 kinds selected from the following divalent O H H O H. H. O. H. group C-2. -C=N-N-C-, -N-C-N-, | || | || | 0357 Divalent Group C-1 the Following Formulas: H H. O H. O. H

--- - CC- - CEN H. H. H -C-O-, -C-N-N-, -NEN- --- | | O O H. H. O S -C=N-N-, X--- H H u? H.| O|| H O O N H

-O- -S- -S- -S- | | O O

-C- - C - - C- - C H O S N-H 0362 wherein a bond at the left end binds to ring Z and a bond at the right end binds to E. US 2006/0122243 A1 Jun. 8, 2006

0363 The group represented by the following formula is 0368 Examples of the substituent in the definition of “an most preferred: arene which may have one or more Substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group -C-N- represented by formula —X-E wherein each of X and E has the same meaning as that defined above' in the aforemen tioned definition of ring Z include similar groups to the substituent explained for the definition “which may be substituted.” The position of substituents existing on the 0364 wherein the bond at the left end binds to ring Zand arene is not particularly limited, and when two or more the bond at the right end binds to E. substituents exist, they may be the same or different. 0365 Examples of the substituent, according to “con necting group which may be substituted in the definition of 0369. When “an arene which may have one or more “a connecting group whose number of atoms of the main Substituents in addition to the group represented by formula chain is 2 to 5.' include similar groups to the Substituents in —O-A wherein A has the same meaning as that defined the definition of the aforementioned “which may be substi above and the group represented by formula —X-E wherein tuted.” A C to C alkyl group is preferred, and a methyl each of X and E has the same meaning as that defined above group is more preferred. The substituent may combine with in the aforementioned definition of ring Z is “a benzene ring a substituent of the ring E or Z, together with atoms to which which may have one or more substituents in addition to the they bind, to form a cyclic group which may be substituted. group represented by formula —O-A wherein A has the Examples include the compounds represented by the general same meaning as that defined above and the group repre formula (I) being those represented by the following for sented by formula —X-E wherein each of X and E has the mulas: same meaning as that defined above.”"a benzene ring which has one to three Substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by CF formula —X-E wherein each of X and E has the same meaning as that defined above' is preferred, and “a benzene OH O ring which has one Substituent in addition to the group represented by formula —O-A wherein A has the same l N s meaning as that defined above and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined above' is more preferred. Preferred examples of said Substituents include groups selected from Br the following Substituent Group Y-1Z. Halogen atom and O tert-butyl group (1,1-dimethyl)ethyl group are more pre N O ferred, and halogen atom is most preferred. \ / 0370. Substituent Group Y-1Z halogen atom, nitro group, cyano group, hydroxy group, methoxy group, OH O methyl group, isopropyl group, tert-butyl group, 1,1,3,3- tetramethylbutyl group, 2-phenylethen-1-yl group, 2.2- dicyanoethen-1-yl group, 2-cyano-2-(methoxycarbon N yl)ethen-1-yl group, 2-carboxy-2-cyanoethen-1-yl group, H ethynyl group, phenylethynyl group, (trimethylsilyl)ethy nyl group, trifluoromethyl group, pentafluoroethyl group, phenyl group, 4-(trifluoromethyl)phenyl group, 4-fluo Br rophenyl group, 2,4-difluorophenyl group, 2-phenethyl group, 1-hydroxyethyl group, 1-(methoxyimino)ethyl 0366. In the aforementioned general formula (I), group, 1-(benzyloxy)iminoethyl group, 2-thienyl group examples of A include hydrogen atom or acetyl group, and thiophen-2-yl group, 3-thienyl group thiophen-3-yl hydrogen atom is preferred. group). 1-pyrrolyl group pyrrol-1-yl group, 2-methylthi azol-4-yl group, imidazol-2-apyridin-2-yl group, 2-py 0367 Examples of the “arene' in “an arene which may ridyl group pyridin-2-yl group, acetyl group, isobutyryl have one or more substituents in addition to the group group, piperidinocarbonyl group, 4-benzylpiperidinocar represented by formula —O-A wherein A has the same bonyl group, (pyrrol-1-yl)sulfonyl group, carboxy group, meaning as that defined above and the group represented by methoxycarbonyl group, N-3,5-bis(trifluoromethyl)phe formula —X-E wherein each of X and E has the same nylcarbamoyl group, N,N-dimethylcarbamoyl group, meaning as that defined above' in the definition of ring Z sulfamoyl group, N-3,5-bis(trifluoromethyl)phenylsul include a monocyclic or fused heterocyclic aromatic hydro famoyl group, N,N-dimethylsulfamoyl group, amino carbon, and include, for example, benzene ring, naphthalene group, N,N-dimethylamino group, acetylamino group, ring, anthracene ring, phenanthrene ring, and acenaphylene benzoylamino group, methanesulfonylamino group, ben ring. C to Co. arenes such as benzene ring, naphthalene ring Zenesulfonylamino group, 3-phenylureido group, (3-phe and the like are preferred, benzene ring and naphthalene ring nyl)thioureido group, (4-nitrophenyl)diaZenyl group, and are more preferred, and benzene ring is most preferred. {4-(pyridin-2-yl)sulfamoylphenyldiazenyl group US 2006/0122243 A1 Jun. 8, 2006 26

0371 When “an arene which may have one or more group, methanesulfonylamino group, benzenesulfony Substituents in addition to the group represented by formula lamino group, 3-phenylureido group, (3-phenyl)thioure —O-A wherein A has the same meaning as that defined ido group, (4-nitrophenyl)diazenyl group, and {4-(pyri above and the group represented by formula —X-E wherein din-2-yl)sulfamoylphenyldiazenyl group each of X and E has the same meaning as that defined above' in the aforementioned definition of ring Z is “a benzene ring 0375 When “an arene which may have one or more which may have one or more substituents in addition to the Substituents in addition to the group represented by formula group represented by formula —O-A wherein A has the —O-A wherein A has the same meaning as that defined same meaning as that defined above and the group repre above and the group represented by formula —X-E wherein sented by formula —X-E wherein each of X and E has the each of X and E has the same meaning as that defined above same meaning as that defined above,” it is most preferable in the aforementioned definition of ring Z is “a naphthalene that one substituent exists and locates on the position of R, ring which may have one or more substituents in addition to when the following partial formula (IZ-1) in the general the group represented by formula —O-A wherein A has the formula containing ring Z same meaning as that defined above and the group repre sented by formula —X-E wherein each of X and E has the same meaning as that defined above.' naphthalene ring is (IZ-1) preferred. 0376 Examples of the “hetero arene' in “a hetero arene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group repre sented by formula —X-E wherein each of X and E has the same meaning as that defined above' in the aforementioned 0372) is represented by the following formula (IZ-2). definition of ring Z include a monocyclic or a fused poly cyclic aromatic heterocyclic rings containing at least one of 1 to 3 kinds of heteroatoms selected from oxygen atom, (IZ-2) Sulfur atom and nitrogen atom and the like as ring-consti No tuting atoms (ring forming atoms), and include, for example, furan ring, thiophene ring, pyrrole ring, oxazole ring, isox azole ring, thiazole ring, isothiazole ring, imidazole ring, pyrazole ring, 1.2.3-oxadiazole ring, 1.2.3-thiadiazole ring, 1,2,3-triazole ring, pyridine ring, pyridazine ring, pyrimi dine ring, pyrazine ring, 1.2.3-triazine ring, 1,2,4-triazine ring, 1 H-azepine ring, 1,4-oxepine ring, 1.4-thiazepine ring, benzofuran ring, isobenzofuran ring, benzobthiophene ring, benzocthiophene ring, indole ring, 2H-isoindole ring, 0373 At this time, said substituents can be defined as R. 1H-indazole ring, 2H-indazole ring, benzoxazole ring, 1.2- Preferred examples of R include a group selected from benzisoxazole ring, 2.1-benzisoxazole ring, benzothiazole the following Substituent Group Y-2Z. Halogen atom and ring, 1.2-benzisothiazole ring, 2.1-benzisothiazole ring, 1.2, tert-butyl group are more preferred, and halogen atom is 3-benzoxadiazol ring, 2,1,3-benzoxadiazol ring, 1.2.3-ben most preferred. Zothiadiazole ring, 2,1,3-benzothiadiazole ring, 1 H-benzot riazole ring, 2H-benzotriazole ring, quinoline ring, 0374 Substituent Group Y-2Z halogen atom, nitro isoquinoline ring, cinnoline ring, quinazoline ring, quinoxa group, cyano group, methoxy group, methyl group, iso line ring, phthalazine ring, naphthyridine ring, 1H-1,5-ben propyl group, tert-butyl group, 1,1,3,3-tetramethylbutyl Zodiazepine ring, carbazole ring, C-carboline ring, B-carbo group, 2-phenylethen-1-yl group, 2,2-dicyanoethen-1-yl line ring, Y-carboline ring, acridine ring, phenoxazine ring, group, 2-cyano-2-(methoxycarbonyl)ethen-1-yl group, phenothiazine ring, phenazine ring, phenanthridine ring, 2-carboxy-2-cyanoethen-1-yl group, ethynyl group, phe phenanthroline ring, thianthrene ring, indolizine ring, and nylethynyl group, (trimethylsilyl)ethynyl group, trifluo phenoxathiine ring, which are 5 to 14-membered monocy romethyl group, pentafluoroethyl group, phenyl group, clic or fused polycyclic aromatic heterocyclic rings. 5 to 4-(trifluoromethyl)phenyl group, 4-fluorophenyl group, 13-membered monocyclic or fused polycyclic aromatic het 2,4-difluorophenyl group, 2-phenethyl group, 1-hydroxy erocyclic rings are preferred, and thiophene ring, pyridine ethyl group, 1-(methoxyimino)ethyl group, 1-(benzy ring, indole ring, quinoxaline ring, and carbazole ring are loxy)iminoethyl group, 2-thienyl group, 3-thienyl group, more preferred. 1-pyrrolyl group, 2-methylthiazol-4-yl group, imidazol, 2-apyridin-2-yl group, 2-pyridyl group, acetyl group, 0377 Examples of the substituent in the definition of “a isobutyryl group, piperidinocarbonyl group, 4-benzylpi hetero arene which may have one or more Substituents in peridinocarbonyl group, (pyrrol-1-yl)sulfonyl group, car addition to the group represented by formula—O-A wherein boxy group, methoxycarbonyl group, N-3,5-bis(trifluo A has the same meaning as that defined above and the group romethyl)phenylcarbamoyl grOup, N,N- represented by formula —X-E wherein each of X and E has dimethylcarbamoyl group, sulfamoyl group, N-3,5- the same meaning as that defined above' in the aforemen bis(trifluoromethyl)phenylsulfamoyl group, N.N- tioned definition of ring Z include similar groups to the dimethylsulfamoyl group, amino group, N.N- substituent explained for the aforementioned definition dimethylamino group, acetylamino group, benzoylamino “which may be substituted.” The position of substituents US 2006/0122243 A1 Jun. 8, 2006 27 existing on the hetero arene is not particularly limited, and dinitrophenyl group, 2,5-bis(1,1-dimethyl)ethylphenyl when two or more Substituents exist, they may be the same group, 5-(1,1-dimethyl)ethyl-2-methoxyphenyl group, or different. 3,5-dimethylphenyl group, 4-methoxybiphenyl-3-yl 0378 Halogen atoms are preferred as the substituent in group, 3,5-dimethoxyphenyl group, 3.5-bis(methoxycar the definition of “a hetero arene which may have one or bonyl)phenyl group, 2-bromo-5-(trifluoromethyl)phenyl more substituents in addition to the group represented by grOup, 3-methoxycarbonyl-5-(trifluoromethyl)phenyl formula —O-A wherein A has the same meaning as that group, 3-carboxy-5-(trifluoromethyl)phenyl group, 2-(2- defined above and the group represented by formula —X-E naphthyloxy)-5-(trifluoromethyl)phenyl group, 2-(2,4- wherein each of X and E has the same meaning as that dichlorophenoxy)-5-(trifluoromethyl)phenyl group, 2-4- defined above' in the aforementioned definition of ring Z. (trifluoromethyl)piperidin-1-yl-5- (trifluoromethyl)phenyl group, 2-(2.2.2-trifluoroethoxy)- 0379 Examples of the aryl group of “an aryl group which 5-(trifluoromethyl)phenyl group, 2-(2-methoxyphenoxy)- may be substituted in the definition of E include similar 5-(trifluoromethyl)phenyl grOup, 2-(4-chloro-3,5- groups to the aryl group in the definition of the aforemen dimethylphenoxy)-5-(trifluoromethyl)phenyl grOup, tioned "hydrocarbon group.’ and C to Co aryl groups such 2-piperidino-5-(trifluoromethyl)phenyl group, 2-(4-meth as phenyl group, 1-naphthyl group, 2-naphthyl group and the ylphenoxy)-5-(trifluoromethyl)phenyl group, 2-(4-chlo like are preferred, and phenyl group is most preferred. rophenoxy)-5-(trifluoromethyl)phenyl group, 3,5-dicar 0380 Examples of the substituent in the definition of “an boxyphenyl group, 5-isopropyl-2-methylphenyl group, aryl group which may be substituted in the definition of E 2,5-diethoxyphenyl group, 2,5-dimethylphenyl group, include similar groups to the Substituent explained for the 5-chloro-2-cyano group, 5-diethylsulfamoyl-2-methoX definition “which may be substituted.” The position of yphenyl group, 2-chloro-5-nitrophenyl group, 2-meth Substituents existing on the aryl group is not particularly oxy-5-(phenylcarbamoyl)phenyl group, 5-acetylamino-2- limited, and when two or more Substituents exist, they may methoxyphenyl group, 5-methoxy-2-methylphenyl group, be the same or different. 2,5-dibutoxyphenyl group, 2,5-diisopentyloxy group, 5-carbamoyl-2-methoxyphenyl group, 5-(1,1-dimethyl 0381. When “an aryl group which may be substituted in )propyl)-2-phenoxyphenyl group, 2-hexyloxy-5-meth the aforementioned definition of E is “a phenyl group which anesulfonyl group, 5-(2,2-dimethylpropionyl)-2-meth may be substituted,'a mono-substituted phenyl group.”“a ylphenyl group, 5-methoxy-2-(1-pyrrolyl)phenyl group, di-substituted phenyl group, and “a phenyl group which has 5-chloro-2-(p-toluenesulfonyl)phenyl group, 2-chloro-5- three or more substituents’ are preferred, and “a di-substi (p-toluenesulfonyl)phenyl group, 2-fluoro-5-methane tuted phenyl group' is more preferred. Sulfonyl group, 2-methoxy-5-phenoxy group, 4-methyl 0382. When “an aryl group which may be substituted in biphenyl-3-yl grOup, 2-methoxy-5-(1-methyl-1- the aforementioned definition of E is “a di-substituted phe phenylethyl)phenyl group, 5-morpholino-2-nitrophenyl nyl group.” preferred examples of the group include groups group, 5-fluoro-2-(1-imidazolyl)phenyl group, 2-butyl-5- represented by the following Substituent Group 6-1e. nitrophenyl group, 5-(1,1-dimethyl)propyl-2-hydrox yphenyl group, 2-methoxy-5-methylphenyl group, 2.5- 0383 Substituent Group 8-1e 3,5-bis(trifluorometh difluorophenyl grOup, 4-isopropyl-2- yl)phenyl group, 3,4-propylenedioxyphenyl group, 3.5- (trifluoromethyl)phenyl grOup, 2-nitro-4- dichlorophenyl group, 2,4-dihydroxyphenyl group, 2.5- (trifluoromethyl)phenyl grOup, 4-bromo-3- dimethoxyphenyl grOup, 2-chloro-5- (trifluoromethyl)phenyl grOup, 4-bromo-2- (trifluoromethyl)phenyl grOup, 3,5-bis(1,1- (trifluoromethyl)phenyl grOup, 2-bromo-4- dimethyl)ethylphenyl grOup, 2.5- (trifluoromethyl)phenyl grOup, 4-fluoro-2- bis(trifluoromethyl)phenyl grOup, 4-chloro-2- (trifluoromethyl)phenyl grOup, 4-isopropoxy-2- (trifluoromethyl)phenyl grOup, 2-fluoro-3- (trifluoromethyl)phenyl grOup, 4-cyano-2- (trifluoromethyl)phenyl grOup, 4-fluoro-3- (trifluoromethyl)phenyl group, 2,6-diisopropylphenyl (trifluoromethyl)phenyl grOup, 4-chloro-3- group, 2,6-dimethylphenyl group, 3,4-dimethylphenyl (trifluoromethyl)phenyl grOup, 3-fluoro-5- group, 2,4-dichlorophenyl group, 2,3-dimethylphenyl (trifluoromethyl)phenyl grOup, 3-bromo-5- group, indan-5-yl group, 2,4-dimethylphenyl group, 2,6- (trifluoromethyl)phenyl grOup, 2-fluoro-5- dichlorophenyl group, 4-bromo-2-(trifluoromethoxy)phe (trifluoromethyl)phenyl grOup, 4-nitro-3- nyl group, 3,4-ethylenedioxyphenyl group, 3-chloro-4- (trifluoromethyl)phenyl grOup, 2-nitro-5- cyanophenyl group, 3-chloro-4-(trifluoromethoxy)phenyl (trifluoromethyl)phenyl grOup, 4-cyano-3- group, 2-chloro-4-cyanophenyl group, 2,3-dichlorophe (trifluoromethyl)phenyl grOup, 2-methyl-3- nyl group, 4-isopropyl-3-methylphenyl group, 4-(1,1- (trifluoromethyl)phenyl grOup, 4-methyl-3- dimethyl)propyl-2-hydroxyphenyl group, 3-chloro-2-cy (trifluoromethyl)phenyl grOup, 2-methyl-5- anophenyl group, 2-cyano-4-methylphenyl group, 2.2- (trifluoromethyl)phenyl grOup, 4-methoxy-3- difluoro-1,3-benzodioxol-4-yl group, 2,2,3,3-tetrafluoro (trifluoromethyl)phenyl grOup, 3-methoxy-5- 1,4-benzodioxen-5-yl grOup, 3-chloro-4- (trifluoromethyl)phenyl grOup, 2-methoxy-5- (trifluoromethylsulfanyl)phenyl grOup, 2-nitro-4- (trifluoromethyl)phenyl group, 2-methylsulfanyl-5- (trifluoromethoxy)phenyl grOup, 2,2-difluoro-1,3- (trifluoromethyl)phenyl group, 2-(1-pyrrolidinyl)-5- benzodioxol-5-yl grOup, 2-methyl-4- (trifluoromethyl)phenyl grOup, 2-morpholino-5- (trifluoromethoxy)phenyl group, 4-bromo-2-fluorophenyl (trifluoromethyl)phenyl grOup, 2-chloro-4- group, 2,4-bis(methanesulfonyl)phenyl group, 2,2,3,3-tet (trifluoromethyl)phenyl group, 2,5-dichlorophenyl group, rafluoro-1,4-benzodioxen-6-yl group, 2-benzoyl-4-chlo 3,4-dichlorophenyl group, 3,5-difluorophenyl group, 3.5- rophenyl group, 2-bromo-4-fluorophenyl group, 3,4- US 2006/0122243 A1 Jun. 8, 2006 28

dimethoxyphenyl group, 3,4-difluorophenyl group, phenyl group.”“a 2,5-di-Substituted phenyl group wherein at 3-chloro-4-methoxyphenyl group, 2-chloro-4-nitrophenyl least one of said substituents is trifluoromethyl group' is group, 2,4-difluorophenyl group, 2-benzoyl-5-methylphe more preferred, a group selected from the following Sub nyl group, 2-bromo-4-(trifluoromethoxy)phenyl group, stituent Group 6-3e is further preferred, and 2.5-bis(trifluo 3,4-dihexyloxyphenyl group, 2,4-bis(trifluorometh romethyl)phenyl group is most preferred. yl)phenyl group, 4-cyano-2-(trifluoromethoxy)phenyl 0388 Substituent Group 6-3e 2-chloro-5-(trifluorom group, 2-(4-cyanophenoxy)-5-(trifluoromethyl)phenyl ethyl)phenyl group, 2,5-bis(trifluoromethyl)phenyl group, and 2-(4-methoxyphenoxy)-5-(trifluorometh group, 2-fluoro-5-(trifluoromethyl)phenyl group, 2-nitro yl)phenyl group 5-(trifluoromethyl)phenyl group, 2-methyl-5-(trifluorom 0384. When “an aryl group which may be substituted in ethyl)phenyl group, 2-methoxy-5-(trifluoromethyl)phenyl the aforementioned definition of E is “a di-substituted phe grOup, 2-methylsulfanyl-5-(trifluoromethyl)phenyl nyl group.”“a 2,5-di-substituted phenyl group, and “a 3.5- grOup, 2-(1-pyrrolidinyl)-5-(trifluoromethyl)phenyl di-substituted phenyl group' are preferred. group, 2-morpholino-5-(trifluoromethyl)phenyl group, 2-bromo-5-(trifluoromethyl)phenyl group, 2-(2-naphthy 0385) When “an aryl group which may be substituted in loxy)-5-(trifluoromethyl)phenyl group, 2-(2,4-dichlo the aforementioned definition of E is “a 2,5-di-substituted rophenoxy)-5-(trifluoromethyl)phenyl group, 2-4-(trif phenyl group.” preferred examples of the group include luoromethyl)piperidin-1-yl)-5-(trifluoromethyl)phenyl groups represented by the following Substituent Group 6-2e. group, 2-(2.2.2-trifluoroethoxy)-5-(trifluoromethyl)phe 0386 Substituent Group 6-2e 2,5-dimethoxyphenyl nyl group, 2-(2-methoxyphenoxy)-5-(trifluorometh group, 2-chloro-5-(trifluoromethyl)phenyl group, 2.5-bis yl)phenyl group, 2-(4-chloro-3,5-dimethylphenoxy)-5- (trifluoromethyl)phenyl group, 2-fluoro-5-(trifluorometh (trifluoromethyl)phenyl grOup, 2-piperidino-5- yl)phenyl group, 2-nitro-5-(trifluoromethyl)phenyl group, (trifluoromethyl)phenyl group, 2-(4-methylphenoxy)-5- 2-methyl-5-(trifluoromethyl)phenyl group, 2-methoxy-5- (trifluoromethyl)phenyl group, 2-(4-chlorophenoxy)-5- (trifluoromethyl)phenyl group, 2-methylsulfanyl-5-(trif (trifluoromethyl)phenyl group, 2-(4-cyanophenoxy)-5- luoromethyl)phenyl group, 2-(1-pyrrolidinyl)-5-(trifluo (trifluoromethyl)phenyl grOup, and 2-(4- romethyl)phenyl grOup, 2-morpholino-5- methoxyphenoxy)-5-(trifluoromethyl)phenyl group (trifluoromethyl)phenyl group, 2,5-dichlorophenyl group, 0389. When “an aryl group which may be substituted in 2.5-bis( 1,1-dimethyl)ethylphenyl group, 5-(1,1-dim the aforementioned definition of E is “a 3,5-di-substituted ethyl)ethyl-2-methoxyphenyl group, 4-methoxybiphe phenyl group.” preferred examples of the group include nyl-3-yl group, 2-bromo-5-(trifluoromethyl)phenyl groups represented by the following Substituent Group 6-4e. grOup, 2-(2-naphthyloxy)-5-(trifluoromethyl)phenyl group, 2-(2,4-dichlorophenoxy)-5-(trifluoromethyl)phe 0390 Substituent Group 8-4e 3,5-bis(trifluorometh nyl group, 2-4-(trifluoromethyl)piperidin-1-yl)-5-(trif yl)phenyl group, 3,5-dichlorophenyl group, 3.5-bis(1.1- luoromethyl)phenyl group, 2-(2.2.2-trifluoroethoxy)-5- dimethyl)ethylphenyl group, 3-fluoro-5-(trifluorometh (trifluoromethyl)phenyl group, 2-(2-methoxyphenoxy)-5- yl)phenyl group, 3-bromo-5-(trifluoromethyl)phenyl (trifluoromethyl)phenyl grOup, 2-(4-chloro-3,5- group, 3-methoxy-5-(trifluoromethyl)phenyl group, 3.5- dimethylphenoxy)-5-(trifluoromethyl)phenyl grOup, difluorophenyl group, 3,5-dinitrophenyl group, 3,5-dim 2-piperidino-5-(trifluoromethyl)phenyl group, 2-(4-meth ethylphenyl group, 3,5-dimethoxyphenyl group, 3,5-bis ylphenoxy)-5-(trifluoromethyl)phenyl group, 2-(4-chlo (methoxycarbonyl)phenyl group, 3-methoxycarbonyl-5- rophenoxy)-5-(trifluoromethyl)phenyl group, 5-isopro (trifluoromethyl)phenyl grOup, 3-carboxy-5- pyl-2-methylphenyl group, 2,5-diethoxyphenyl group, (trifluoromethyl)phenyl group, and 3,5-dicarboxyphenyl 2,5-dimethylphenyl group, 5-chloro-2-cyano group, 5-di group ethylsulfamoyl-2-methoxyphenyl group, 2-chloro-5-ni 0391) When “an aryl group which may be substituted in trophenyl group, 2-methoxy-5-(phenylcarbamoyl)phenyl the aforementioned definition of E is “a 3,5-di-substituted group, 5-acetylamino-2-methoxyphenyl group, 5-meth phenyl group.”“a 3,5-di-substituted phenyl group wherein at oxy-2-methylphenyl group, 2,5-dibutoxyphenyl group, least one of said substituents is trifluoromethyl group' is 2,5-diisopentyloxy group, 5-carbamoyl-2-methoxyphenyl more preferred, a group selected from the following Sub group, 5-(1,1-dimethyl)propyl)-2-phenoxyphenyl group, stituent Group 6-5e is further preferred, and 3,5-bis(trifluo 2-hexyloxy-5-methanesulfonyl group, 5-(2,2-dimethyl romethyl)phenyl group is most preferred. propionyl)-2-methylphenyl group, 5-methoxy-2-(1-pyr rolyl)phenyl group, 5-chloro-2-(p-toluenesulfonyl)phenyl 0392 Substituent Group 8-5e 3,5-bis(trifluorometh group, 2-chloro-5-(p-toluenesulfonyl)phenyl group, yl)phenyl group, 3-fluoro-5-(trifluoromethyl)phenyl 2-fluoro-5-methanesulfonyl group, 2-methoxy-5-phenoxy group, 3-bromo-5-(trifluoromethyl)phenyl group, 3-meth grOup, 2-methoxy-5-(1-methyl-1-phenylethyl)phenyl oxy-5-(trifluoromethyl)phenyl group, 3-methoxycarbo group, 5-morpholino-2-nitrophenyl group, 5-fluoro-2-(1- nyl-5-(trifluoromethyl)phenyl group, and 3-carboxy-5- imidazolyl)phenyl group, 2-butyl-5-nitrophenyl group, (trifluoromethyl)phenyl group 5-(1,1-dimethyl)propyl)-2-hydroxyphenyl grOup, 0393) When “an aryl group which may be substituted” in 2-methoxy-5-methylphenyl group, 2,5-difluorophenyl the aforementioned definition of E is “a mono-substituted group, 2-benzoyl-5-methylphenyl group, 2-(4-cyanophe phenyl group.” preferred examples of the group include noxy)-5-(trifluoromethyl)phenyl group, and 2-(4-methoX groups represented by the following Substituent Group 6-6e. yphenoxy)-5-(trifluoromethyl)phenyl group 0394 Substituent Group 8-6e 4-methoxyphenyl group, 0387 When “an aryl group which may be substituted in 4-chlorophenyl group, 2-methoxyphenyl group, 2-(trif the aforementioned definition of E is “a 2,5-di-substituted luoromethyl)phenyl group, 3-(trifluoromethyl)phenyl US 2006/0122243 A1 Jun. 8, 2006 29

group, 4-(trifluoromethyl)phenyl group, 3-chlorophenyl E include similar groups to the "monocyclic heteroaryl group, biphenyl-3-yl group, 3-acetylphenyl group, group' and “fused polycyclic heteroaryl group” in the 3-(acetylamino)phenyl group, 3-carbamoylphenyl group, definition of the aforementioned "heterocyclic group.” A 5 3-methylcarbomoylphenyl group, 4-methylphenyl group, to 13-membered heteroaryl group is preferred, and preferred 3-(trifluoromethoxy)phenyl group, 2-benzylphenyl group, examples of the group include thienyl group, pyrazolyl 4-(trifluoromethoxy)phenyl group, 4-(1,1-dimethyl group, oxazolyl group, 1,3,4-thiadiazolyl group, pyridyl )ethylphenyl group, 3-isopropoxyphenyl group, 4-iso group, pyrimidinyl group, indolyl group, quinolyl group. propoxyphenyl group, 4-hexylphenyl group, 3-meth carbazolyl group, thiazolyl group, and pyrazinyl group. ylphenyl grOup, 4-cyclohexylphenyl grOup, 4-benzylphenyl group, 2-chlorophenyl group, 2-meth 0399. A 5-membered heteroaryl group is more preferred ylphenyl group, 4-butylphenyl group, 4-benzyloxyphenyl as the "heteroaryl group” in “a heteroaryl group which may group, 3-benzylphenyl group, 4-hexyloxyphenyl group, be substituted in the definition of E. Thienyl group, pyra 3-isopropylphenyl group, 4-cyanophenyl group, 3-cy Zolyl group, oxazolyl group, 1,3,4-thiadiazolyl group, and anophenyl group, 4-(ethoxycarbonylmethyl)phenyl thiazolyl group are further preferred, and thiazolyl group is group, 3-(trifluoromethylsulfanyl)phenyl group, 4-(trif most preferred. luoromethylsulfanyl)phenyl group, 4-(trifluoromethane 04.00 Examples of the substituent in the definition of “a Sulfonyl)phenyl group, 3-ethynylphenyl group, 4-(1-me heteroaryl group which may be substituted in the afore thylpropyl)phenyl group, 3-benzoylphenyl group, mentioned definition of E include similar groups to the 3-methoxyphenyl group, 4-(acetylamino)phenyl group, substituent explained for the definition “which may be 4-Sulfamoylphenyl group, 4-difluoromethoxy)phenyl substituted.” The position of substituents existing on the group, 3-methylsulfanylphenyl group, 4-methanesulfo heteroaryl group is not particularly limited, and when two or nylphenyl group, 3-(butylsulfamoyl)phenyl group, 3-ben more substituents exist, they may be the same or different. Zyloxyphenyl group, 4-(p-toluenesulfonylamino)phenyl group, 4-morpholinophenyl group, 3-(1,1-dimethyl 0401 When “a heteroaryl group which may be substi )ethylphenyl group, 3-(5-methylfuran-2-yl)phenyl tuted in the aforementioned definition of E is “a thiazolyl group, 3-sulfamoylphenyl group, 3-(trifluoromethane group which may be substituted.”"a thiazol-2-yl group Sulfonyl)phenyl group, 3-hexyloxyphenyl group, which may be substituted.'" A mono-substituted thiazol-2-yl 4-acetylphenyl group, biphenyl-2-yl group, biphenyl-4-yl group' and “a di-substituted thiazol-2-yl group' are more group, 3-5-phenyl-3-(trifluoromethyl)pyrazol-1-ylphe preferred, and “a di-substituted thiazol-2-yl group' is further nyl group, 3-5-(1,1-dimethyl)ethyl-3-(trifluorometh preferred. yl)pyrazol-1-yl)phenyl group, 4-3,5-bis(trifluorometh 0402. When “a heteroaryl group which may be substi yl)pyrazol-1-ylphenyl grOup, 3-3,5- tuted in the aforementioned definition of E is “a di bis(trifluoromethyl)pyrazol-1-ylphenyl group, and 4-5- Substituted thiazol-2-yl group, a group selected from the phenyl-3-(trifluoromethyl)pyrazol-1-yl)phenyl group following Substituent Group 8-8e is preferred, and 4-(1,1- dimethyl)ethyl-5-(2,2-dimethyl)propionylthiazol-2-yl 0395. When “an aryl group which may be substituted” in group is most preferred. the aforementioned definition of E is “a phenyl group which has three or more substituents, preferred examples of the 0403 Substituent Group 8-8e 5-bromo-4-(1,1-dimeth group include groups represented by the following Substitu yl)ethylthiazol-2-yl group, 5-bromo-4-(trifluorometh ent Group 8-7e. yl)thiazol-2-yl group, 5-cyano-4-(1,1-dimethyl)ethyl thiazol-2-yl group, 5-methylthiazol-2-yl group, 4.5- 0396 Substituent Group 8-7e 3,5-bis(trifluoromethyl)- dimethylthiazol-2-yl group, 5-methyl-4-phenylthiazol-2- 2-bromophenyl group, 3,4,5-trichlorophenyl group, 3.5- yl group, 5-(4-fluorophenyl)-4-methylthiazol-2-yl group, dichloro-4-hydroxyphenyl group, pentafluorophenyl 4-methyl-5-3-(trifluoromethyl)phenylthiazol-2-yl group, 3.5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphtha group, 4-(1,1-dimethyl)ethyl-5-ethylthiazol-2-yl group, len-2-yl group, 3,5-bis(trifluoromethyl)-2-methylphenyl 4-ethyl-5-phenylthiazol-2-yl group, 4-isopropyl-5-phe group, 2,6-dichloro-4-(trifluoromethyl)phenyl group, 2,4- nylthiazol-2-yl group, 4-butyl-5-phenylthiazol-2-yl dimethoxy-5-(trifluoromethyl)phenyl group, 2,4-dif group, 4-(1,1-dimethyl)ethyl-5-(2,2-dimethyl)propio luoro-5-(trifluoromethyl)phenyl group, 4-chloro-2-(4- nylthiazol-2-yl grOup, 4-(1,1-dimethyl)ethyl-5- chlorobenzenesulfonyl)-5-(trifluoromethyl)phenyl group, (ethoxycarbonyl)thiazol-2-yl group, 4-(1,1-dimethyl 5-chloro-2-nitro-4-(trifluoromethyl)phenyl group, 2,3-di )ethyl-5-piperidinothiazol-2-yl grOup, 4-(1,1- fluoro-4-(trifluoromethyl)phenyl group, 2,3,5,6-tet dimethyl)ethyl-5-morpholinothiazol-2-yl group, 4-(1,1- rafluoro-4-(trifluoromethyl)phenyl group, 2,4,6-trimeth dimethyl)ethyl-5-(4-methylpiperazin-1-yl)thiazol-2-yl ylphenyl group, 2-cyano-4,5-dimethoxyphenyl group, group, 4-(1,1-dimethyl)ethyl-5-(4-phenylpiperazin-1- 2,4-dichloro-5-isopropoxyphenyl group, 2,3,5-trifluo yl)thiazol-2-yl group, 5-carboxymethyl-4-phenylthiazol rophenyl group, 2,4,5-trichlorophenyl group, and 2-yl group, 4.5-diphenylthiazol-2-yl group, 4-benzyl-5- 5-ethoxy-4-fluoro-2-nitrophenyl group phenylthiazol-2-yl grOup, 5-phenyl-4- (trifluoromethyl)thiazol-2-yl grOup, 5-acetyl-4- 0397) When “an aryl group which may be substituted” in phenylthiazol-2-yl group, 5-benzoyl-4-phenylthiazol-2-yl the aforementioned definition of E is “a naphthyl group group, 5-ethoxycarbonyl-4-phenylthiazol-2-yl group, which may be substituted, preferred examples of the group 5-ethoxycarbonyl-4-(pentafluorophenyl)thiazol-2-yl include 1-naphthyl group, 4-methoxynaphthalen-2-yl group, group, 5-methylcarbamoyl-4-phenylthiazol-2-yl group, and 4-hydroxy-3-methylnaphthalen-1-yl group. 5-ethylcarbamoyl-4-phenylthiazol-2-yl group, 5-isopro 0398. Examples of the “heteroaryl group” in “a het pylcarbamoyl-4-phenylthiazol-2-yl group, 5-(2-phenyl eroaryl group which may be substituted in the definition of ethyl)carbamoyl-4-phenylthiazol-2-yl group, 5-ethoxy US 2006/0122243 A1 Jun. 8, 2006 30

carbonyl-4-(trifluoromethyl)thiazol-2-yl grOup, group, methanesulfonylamino group, benzenesulfony 5-carboxy-4-(1,1-dimethyl)ethylthiazol-2-yl grOup, lamino group, 3-phenylureido group, (3-phenyl)thioure 5-(ethoxycarbonyl)methyl-4-phenylthiazol-2-yl group, ido group, (4-nitrophenyl)diazenyl group, and {4-(pyri 5-carboxy-4-phenylthiazol-2-yl group, and 5-propylcar din-2-yl)sulfamoylphenyl diazenyl group bamoyl-4-phenylthiazol-2-yl group. 0411 “2-Acetoxyphenyl group which is substituted in the 0404 When “a heteroaryl group which may be substi 5-position is preferred as the “2-acetoxyphenyl group tuted in the aforementioned definition of E is “a mono which may be substituted in the 5-position' in the definition substituted thiazol-2-yl group.' preferred examples of the of Z'. group include groups represented by the following Substitu 0412. A halogen atom is preferred as the substituent in ent Group 8-9e. the definition of “2-acetoxyphenyl group which may be 04.05 Substituent Group 8-9e 4-(1,1-dimethyl)ethyl substituted in the 5-position' and “2-acetoxyphenyl group thiazol-2-yl group, 4-phenylthiazol-2-yl group, 4-3.5- which is substituted in the 5-position” in the definition of Z'. bis(trifluoromethyl)phenylthiazol-2-yl group, 4-(2,4- dichlorophenyl)thiazol-2-yl grOup, 4-(3,4- 0413) The definition “which may be substituted” in the dichlorophenyl)thiazol-2-yl grOup, 4-4- definition of “a phenyl group which may be substituted in (trifluoromethyl)phenylthiazol-2-yl group, 4-(2,5- the definition of E has the same meaning as “which may be difluorophenyl)thiazol-2-yl grOup, 4-(4- substituted.” methoxyphenyl)thiazol-2-yl grOup, 4-3- 0414 Examples of the substituent in the definition of “a (trifluoromethyl)phenylthiazol-2-yl grOup, and phenyl group which may be substituted in the definition of 4-(pentafluorophenyl)thiazol-2-yl group E' include similar groups to the substituents explained for the definition “which may be substituted.” A position of a 0406. The compounds represented by the aforementioned Substituent existing on the phenyl group is not particularly general formula (I-1) are explained in details. limited, and when two or more Substituents exist, they may 04.07 Examples of the substituent in the definition of be the same or different. “2-hydroxyphenyl group which may be substituted in the 0415 Preferred examples of “a phenyl group which may 5-position' and “2-acetoxyphenyl group which may be be substituted” in the definition of E' include 3,5-bis(trif substituted in the 5-position” in the definition of Z' include luoromethyl)phenyl group, 2,5-bis(trifluoromethyl)phenyl similar groups to the substituent explained for the definition group, a phenyl group which has three or more substituents “which may be substituted.” wherein at least one of said substituents is trifluoromethyl 0408 “2-Hydroxyphenyl group which is substituted in group, and a di-substituted phenyl group wherein at least one the 5-position' is preferred as the “2-hydroxyphenyl group of said substituents is trifluoromethyl group, (provided that which may be substituted in the 5-position' in the definition a 2,5-di-substituted phenyl group and a 3,5-di-substituted of Z'. phenyl group are excluded as said di-substituted phenyl group.) 3.5-Bis(trifluoromethyl)phenyl group and 2.5-bis 04.09 Preferred examples of the substituent in the defi nition of “2-hydroxyphenyl group which may be substituted (trifluoromethyl)phenyl group are more preferred. in the 5-position' and “2-hydroxyphenyl group which is 0416) When “a phenyl group which may be substituted” substituted in the 5-position” in the definition of Z' include in the definition of E is “a phenyl group which has three or a group selected from the following Substituent Group more substituents wherein at least one of said substituents is Y'-1Z. A halogen atom and tert-butyl group are more pre trifluoromethyl group.” preferred examples of the group ferred, and a halogen atom is most preferred. include groups represented by the following Substituent 0410) Substituent Group Y'-1z) a halogen atom, nitro Group o'-le. group, cyano group, methoxy group, methyl group, iso 0417. Substituent Group 8'-1e3,5-bis(trifluoromethyl)- propyl group, tert-butyl group, 1,1,3,3-tetramethylbutyl 2-bromophenyl group, 3,5-bis(trifluoromethyl)-2-meth group, 2-phenylethen-1-yl group, 2,2-dicyanoethen-1-yl ylphenyl group, 2,6-dichloro-4-(trifluoromethyl)phenyl group, 2-cyano-2-(methoxycarbonyl)ethen-1-yl group, group, 2,4-dimethoxy-5-(trifluoromethyl)phenyl group, 2-carboxy-2-cyanoethen-1-yl group, ethynyl group, phe 2,4-difluoro-5-(trifluoromethyl)phenyl group, 4-chloro-2- nylethynyl group, (trimethylsilyl)ethynyl group, trifluo (4-chlorobenzenesulfonyl)-5-(trifluoromethyl)phenyl romethyl group, pentafluoroethyl group, phenyl group, group, 5-chloro-2-nitro-4-(trifluoromethyl)phenyl group, 4-(trifluoromethyl)phenyl group, 4-fluorophenyl group, 2,3-difluoro-4-(trifluoromethyl)phenyl group, and 2.3.5, 2,4-difluorophenyl group, 2-phenethyl group, 1-hydroxy 6-tetrafluoro-4-(trifluoromethyl)phenyl group ethyl group, 1-(methoxyimino)ethyl group, 1-(benzy loxy)iminoethyl group, 2-thienyl group, 3-thienyl group, 0418 When “a phenyl group which may be substituted” 1-pyrrolyl group, 2-methylthiazol-4-yl group, imidazol, in the definition of E' is "a di-substituted phenyl group 2-apyridin-2-yl group, 2-pyridyl group, acetyl group, wherein at least one of said substituents is trifluoromethyl isobutyryl group, piperidinocarbonyl group, 4-benzylpi group, (provided that a 2,5-di-substituted phenyl group and peridinocarbonyl group, (pyrrol-1-yl)sulfonyl group, car a 3,5-di-substituted phenyl group are excluded from said boxy group, methoxycarbonyl group, N-3,5-bis(trifluo di-substituted phenyl group) preferred examples of the romethyl)phenylcarbamoyl grOup, N,N- group include groups represented by the following Substitu dimethylcarbamoyl group, sulfamoyl group, N-3,5- ent Group o'-2e. bis(trifluoromethyl)phenylsulfamoyl group, N.N- 0419) Substituent Group o'-2e) 4-chloro-2-(trifluorom dimethylsulfamoyl group, amino group, N.N- ethyl)phenyl group, 2-fluoro-3-(trifluoromethyl)phenyl dimethylamino group, acetylamino group, benzoylamino grOup, 4-fluoro-3-(trifluoromethyl)phenyl grOup, US 2006/0122243 A1 Jun. 8, 2006 31

4-chloro-3-(trifluoromethyl)phenyl group, 4-nitro-3-(trif grOup, 2-methylsulfanyl-5-(trifluoromethyl)phenyl luoromethyl)phenyl group, 4-cyano-3-(trifluorometh grOup, 2-(1-pyrrolidinyl)-5-(trifluoromethyl)phenyl yl)phenyl group, 2-methyl-3-(trifluoromethyl)phenyl group, 2-morpholino-5-(trifluoromethyl)phenyl group, grOup, 4-methyl-3-(trifluoromethyl)phenyl grOup, 2-bromo-5-(trifluoromethyl)phenyl group, 2-(2-naphthy 4-methoxy-3-(trifluoromethyl)phenyl group, 2-chloro-4- (trifluoromethyl)phenyl group, 4-isopropyl-2-(trifluorom loxy)-5-(trifluoromethyl)phenyl group, 2-(2,4-dichlo ethyl)phenyl group, 2-nitro-4-(trifluoromethyl)phenyl rophenoxy)-5-(trifluoromethyl)phenyl group, 2-4-(trif grOup, 4-bromo-3-(trifluoromethyl)phenyl grOup, luoromethyl)piperidin-1-yl)-5-(trifluoromethyl)phenyl 4-bromo-2-(trifluoromethyl)phenyl group, 2-bromo-4- group, 2-(2.2.2-trifluoroethoxy)-5-(trifluoromethyl)phe (trifluoromethyl)phenyl group, 4-fluoro-2-(trifluorometh nyl group, 2-(2-methoxyphenoxy)-5-(trifluorometh yl)phenyl group, 4-isopropoxy-2-(trifluoromethyl)phenyl yl)phenyl group, 2-(4-chloro-3,5-dimethylphenoxy)-5- group, 4-cyano-2-(trifluoromethyl)phenyl group, and 2,4- (trifluoromethyl)phenyl grOup, 2-piperidino-5- bis(trifluoromethyl)phenyl group (trifluoromethyl)phenyl group, 2-(4-methylphenoxy)-5- (trifluoromethyl)phenyl group, 2-(4-chlorophenoxy)-5- 0420 Compounds represented by the aforementioned (trifluoromethyl)phenyl group, 2-(4-cyanophenoxy)-5- general formula (I-2) are explained in details. (trifluoromethyl)phenyl grOup, and 2-(4- 0421 Examples of the substituent in the definition of methoxyphenoxy)-5-(trifluoromethyl)phenyl group “2-hydroxyphenyl group which may be substituted in the 5-position' and “2-acetoxyphenyl group which may be 0429. A group selected from the following Substituent substituted in the 5-position” in the definition of Z include Group 8-2e is preferred as “a 3,5-di-substituted phenyl similar groups to the substituent explained for the definition group wherein one of said substituents is trifluoromethyl “which may be substituted.” group” in the definition of E. 0422 “2-Hydroxyphenyl group which is substituted in 0430) Substituent Group 8-2e 3,5-bis(trifluorometh the 5-position' is preferred as the “2-hydroxyphenyl group yl)phenyl group, 3-fluoro-5-(trifluoromethyl)phenyl which may be substituted in the 5-position' in the definition group, 3-bromo-5-(trifluoromethyl)phenyl group, 3-meth of Z. oxy-5-(trifluoromethyl)phenyl group, 3-methoxycarbo nyl-5-(trifluoromethyl)phenyl group, and 3-carboxy-5- 0423. A halogen atom, nitro group, methyl group, and (trifluoromethyl)phenyl group methoxy group are preferred as the substituent in the defi nition of “2-hydroxyphenyl group which may be substituted 0431 Compounds represented by the aforementioned in the 5-position' and “2-hydroxyphenyl group which is general formula (I-3) are explained in details. substituted in the 5-position” in the definition of Z, and a 0432 Examples of the substituent in the definition of halogen atom is most preferred. “2-hydroxyphenyl group which may be substituted in the 0424 “2-Acetoxyphenyl group which is substituted in 5-position' and “2-acetoxyphenyl group which may be the 5-position' is preferred as the “2-acetoxyphenyl group substituted in the 5-position” in the definition of Z include which may be substituted in the 5-position' in the definition similar groups to the substituent explained for the definition of Z'. “which may be substituted.” 0425. A halogen atom is preferred as the substituent in 0433 “2-Hydroxyphenyl group which is substituted in the definition of “2-acetoxyphenyl group which may be the 5-position' is preferred as the “2-hydroxyphenyl group substituted in the 5-position' and “2-acetoxyphenyl group which may be substituted in the 5-position' in the definition which is substituted in the 5-position” in the definition of Z. of Z. 0426 Examples of the substituent in the definition of “a 0434. A halogen atom, nitro group, methyl group and 2,5-di-substituted phenyl group wherein one of said sub methoxy group are preferred as the substituent in the defi stituents is trifluoromethyl group' and “a 3,5-di-substituted nition of “2-hydroxyphenyl group which may be substituted phenyl group wherein one of said Substituents is trifluorom in the 5-position' and “2-hydroxyphenyl group which is ethyl group” in the definition of E include similar groups to substituted in the 5-position” in the definition of Z, and a the substituent explained for the definition “which may be halogen atom is most preferred. substituted.” 0435 “2-Acetoxyphenyl group which is substituted in 0427. A group selected from the following Substituent the 5-position' is preferred as the “2-acetoxyphenyl group Group of.-1e is preferred as “a 2,5-di-substituted phenyl which may be substituted in the 5-position' in the definition group wherein one of said substituents is trifluoromethyl of Z. group” in the definition of E. 0436. A halogen atom is preferred as the substituent in 0428 Substituent Group 8-1e 2-chloro-5-(trifluorom the definition of “2-acetoxyphenyl group which may be ethyl)phenyl group, 2,5-bis(trifluoromethyl)phenyl substituted in the 5-position' and “2-acetoxyphenyl group group, 2-fluoro-5-(trifluoromethyl)phenyl group, 2-nitro which is substituted in the 5-position” in the definition of Z. 5-(trifluoromethyl)phenyl group, 2-methyl-5-(trifluorom 0437. Examples of the substituent in the definition of “a ethyl)phenyl group, 2-methoxy-5-(trifluoromethyl)phenyl hydrocarbon group which may be substituted in the defi US 2006/0122243 A1 Jun. 8, 2006 32 nition of R and R and "a C. to Ca hydrocarbon group 0449 Examples of the “acyl group” in the definition of which may be substituted” in the definition of R include “an acyl group which may be substituted in the definition similar groups to the substituent explained for the definition of R' include similar groups to the “acyl group” in the “which may be substituted.” aforementioned definition. 0438 Examples of the “hydrocarbon group' in the defi 0450 Examples of the "heterocyclic group' in the defi nition of “a hydrocarbon group which may be substituted in nition of “a heterocyclic group which may be substituted in the definition of RandR and “a C. to C. hydrocarbon the definition of R include similar groups to the "hetero group which may be substituted” in the definition of R cyclic group' in the aforementioned definition. 0451 A group selected from the following Substituent include similar groups to the “hydrocarbon group” in the Group 8-1e is preferred as E, and 4-(1,1-dimethyl)ethyl aforementioned definition. 5-(2,2-dimethyl)propionylthiazol-2-yl group is most pre 0439 Examples of the “hydroxy group which may be ferred. substituted” in the definition of RandR include similar 0452 Substituent Group 6-1e 5-bromo-4-(1,1-dimeth groups to the “hydroxy group which may be substituted yl)ethylthiazol-2-yl group, 5-bromo-4-(trifluorometh explained for the definition “which may be substituted.” yl)thiazol-2-yl group, 5-cyano-4-(1,1-dimethyl)ethyl 0440 AS E, 3.5-bis(1,1-dimethyl)ethylphenyl group, thiazol-2-yl group, 5-methylthiazol-2-yl group, 4-(1,1- 2.5-bis(1,1-dimethyl)ethylphenyl group, 5-(1,1-dimethyl dimethyl)ethyl-5-(2,2-dimethyl)propionylthiazol-2-yl )ethyl-2-methoxyphenyl group, 4-methoxybiphenyl-3-yl group, 4-(1,1-dimethyl)ethyl-5-(ethoxycarbonyl)thi group, 5-(1,1-dimethyl)propyl)-2-phenoxyphenyl group, azol-2-yl group, 4-(1,1-dimethyl)ethyl-5-piperidinothia 4-methylbiphenyl-3-yl group and 5-(1,1-dimethyl)propyl Zol-2-yl group, 4-(1,1-dimethyl)ethyl-5-morpholi 2-hydroxyphenyl group are preferred, and 3,5-bis(1,1-dim nothiazol-2-yl group, 4-(1,1-dimethyl)ethyl-5-(4- ethyl)ethylphenyl group is more preferred. methylpiperazin-1-yl)thiazol-2-yl grOup, 4-(1,1- dimethyl)ethyl-5-(4-phenylpiperazin-1-yl)thiazol-2-yl 0441 Compounds represented by the aforementioned group, 5-carboxymethyl-4-phenylthiazol-2-yl group, general formula (I-4) are explained in details. 5-acetyl-4-phenylthiazol-2-yl group, 5-benzoyl-4-phe 0442. Examples of the substituent in the definition of nylthiazol-2-yl group, 5-ethoxycarbonyl-4-phenylthiazol “2-hydroxyphenyl group which may be substituted in the 2-yl group, 5-ethoxycarbonyl-4-(pentafluorophenyl)thi 5-position” and “2-acetoxyphenyl group which may be azol-2-yl group, 5-methylcarbamoyl-4-phenylthiazol-2-yl substituted in the 5-position” in the definition of Z' include group, 5-ethylcarbamoyl-4-phenylthiazol-2-yl group, similar groups to the substituent explained for the definition 5-isopropylcarbamoyl-4-phenylthiazol-2-yl group, 5-(2- “which may be substituted.” phenylethyl)carbamoyl-4-phenylthiazol-2-yl grOup, 5-ethoxycarbonyl-4-(trifluoromethyl)thiazol-2-yl group, 0443 “2-Hydroxyphenyl group which is substituted in 5-carboxy-4-(1,1-dimethyl)ethylthiazol-2-yl grOup, the 5-position' is preferred as the “2-hydroxyphenyl group 5-carboxy-4-phenylthiazol-2-yl group, and 5-propylcar which may be substituted in the 5-position' in the definition bamoyl-4-phenylthiazol-2-yl group. of Z. 0453 Among the compound represented by the general 0444. A halogen atom, phenyl group, 4-fluorophenyl formulas (I), (I-1), (1-2), (I-3) and (I-4), preferred com group, 2,4-difluorophenyl group, 4-(trifluoromethyl)phenyl pounds are those other than “substituted benzoic acid deriva group, 1-pyrrolyl group and 2-thienyl group are preferred as tives represented by the following general formula (X-1) the substituent in the definition of “2-hydroxyphenyl group and/or compounds represented by the following Compound which may be substituted in the 5-position' and “2-hydrox Group (p-1.” yphenyl group which is substituted in the 5-position” in the definition of Z, and a halogen atom is most preferred. 0445 “2-Acetoxyphenyl group which is substituted in (X-1) the 5-position' is preferred as the “2-acetoxyphenyl group which may be substituted in the 5-position' in the definition of Z. 0446. A halogen atom is preferred as the substituent in the definition of “2-acetoxyphenyl group which may be substituted in the 5-position' and “2-acetoxyphenyl group 0454) wherein R' represents the following general which is substituted in the 5-position” in the definition of Z. formula (X-2): 0447 Examples of the substituent in the definition of “a hydrocarbon group which may be substituted in the defi (X-2) nition of R', and “an acyl group which may be substituted” and “a heterocyclic group which may be substituted in the R1 003 RI 005 definition of R include similar groups to the substituent explained for the definition “which may be substituted.” 0448 Examples of the “hydrocarbon group' in the defi R1004 CH nition of “a hydrocarbon group which may be substituted in the definition of R include similar groups to the “hydro carbon group' in the aforementioned definition. US 2006/0122243 A1 Jun. 8, 2006 33

0455 or the following general formula (X-3): -continued O (X-3) OR 1009 ON R1003 R1005 N OH R1004 CH 04.59 Each compound defined by the aforementioned OR 1010 general formulas (I-1), (I-2), (I-3), and (I-4), or a pharma cologically acceptable salt thereof, or a hydrate thereof or a Solvate thereof is novel. Uses of the compound according to 0456 wherein each of R', R'' and R' indepen the aforementioned chemical Substance invention are not dently represents hydrogen atom, an alkyl group having particularly limited. from 1 to 6 carbons or an alkoxy group having from 1 to 0460 The compounds represented by the aforementioned 6 carbons, each of R'' and R' independently repre general formulas (I), (I-1), (I-2), (I-3) and (1-4) may form sents hydrogen atom, an alkyl group having from 1 to 6 salts. Examples of pharmacologically acceptable salts carbons, or an acyl group having from 2 to 11 carbons; include, when acidic groups exist, metal salts such as lithium salt, Sodium salt, potassium salt, magnesium salt, calcium 0457) R' represents hydrogen atom, a lower alkyl salts, or ammonium salts such as ammonium salt, methy group having from 1 to 6 carbons, which may be substi lammonium salt, dimethylammonium salt, trimethylammo tuted, an aryl group having from 6 to 12 carbons, which nium salt, dicyclohexylammonium salt, and when basic may be substituted, a heteroaryl group having from 4 to groups exist, mineral acid salts such as hydrochloride, 11 carbons, which may be substituted, an aralkyl group oxalate, hydrosulfate, nitrate, phosphate, or organic acid having from 7 to 14 carbons, which may be substituted, a salts such as methane Sulfonate, benzene Sulfonate, para heteroarylalkyl group having from 5 to 13 carbons, which toluene Sulfonate, acetate, propionate, tartrate, fumarate, may be substituted, or an acyl group having from 2 to 11 maleate, malate, oxalate. Succinate, citrate, benzoate, man delate, cinnamate, lactate. Salts may sometimes be formed carbons; with amino acids such as glycine. As active ingredients of 0458) X' represents carboxy group which may be the medicament of the present invention, pharmacologically esterified or amidated. acceptable salts may also be Suitably used. 0461 The compounds or salts thereof represented by the aforementioned general formulas (I), (I-1), (I-2), (1-3) and Compound Group p-1 (1-4) may exist as hydrates or Solvates. AS active ingredients of the medicament of the present invention, any of the C aforementioned substances may be used. Furthermore, the O compounds represented by the aforementioned general for mulas (I), (I-1). (I-2), (I-3) and (I-4) may sometimes have OH O r N one or more asymmetric carbons, and may exist as Steric N isomers such as optically active Substance and diastereomer. H AS active ingredients of the medicament of the present C’s 21 CF3, invention, pure forms of stereoisomers, arbitrary mixture of enantiomers or diastereomers, and racemates may be used. C 0462 Furthermore, when the compounds represented by O the general formulas (I), (I-1), (I-2), (1-3) and (I-4) has, for OH O N example, 2-hydroxypyridine form, the compounds may exist C N as 2-pyridone form which is a tautomer. As active ingredi N 2 CF, ents of the medicament of the present invention, pure forms H of tautomers or a mixture thereof may be used. When the compounds represented by the general formulas (I), (I-1), (I-2), (I-3) and (I-4) have olefinic double bonds, the con C figuration may be in either E or Z, and as active ingredients of the medicament of the present invention, geometrical C isomer in either of the configurations or a mixture thereof O may be used. OH O N 0463 Examples of the compounds included in the gen OHCHN N eral formulas (I), (I-1), (I-2), (I-3) and (I-4) as active N 4N ingredients of the medicaments of the present invention are shown below. However, the active ingredients of the medi caments of the present invention are not limited to the compound set out below. US 2006/0122243 A1 Jun. 8, 2006 34

0464) The abbreviations used in the following tables have the following meanings. 0465 Me: methyl group, Et: ethyl group.

A

Compound Number C

1 OH O 1S H

Br

2 OH O 1)N-1 H

Br

3 OH

O

B r ul N H

OMe 4 -->

MeO OH

5 OH OH

CC US 2006/0122243 A1 Jun. 8, 2006 35

-continued 6 OH -->O MeODO MeO

7 OH O O

--> COO

Me

8 OH O O

O Me C --> CO No1 No

9 OH 1S1 C

C

10 OH 1. Y6 N

Br

11 OH H C F 3

12 OH H C

C

13 OH C 1

C

C US 2006/0122243 A1 Jun. 8, 2006

-continued

14 OH 1n 1. C

C

Br

15 OH O OH N1

u OH CBr

16 OH O CF

O CF CC

17 OH CF uls,O Br

A No O

E C. N1H

An

Compound Number (r E

18 OH C

O C US 2006/0122243 A1 Jun. 8, 2006

-continued

19 OH C

C

2O OH OMe

OMe 21 OH oCFCF 22 OH SOF

23 OH SOF

NNS N C C 24 OH CF

N N 2 O CF C

25 O H CF3 N 2 C OC US 2006/0122243 A1 Jun. 8, 2006 38

-continued

26 OH Me Me Me N1N 21 Me C Me Me

27 OH CF

CF

28 OH CF 8. O CF 29 OH CF C O CF 30 O

31 32 OH . US 2006/0122243 A1 Jun. 8, 2006 39

-continued

33 OH OMe

C

34 O OMe

C

35 OH EtOC | \ S

C 36 COH -U-ON-NH Br

37 OH Et

Br

38 OH

Br

39 OH

Br US 2006/0122243 A1 Jun. 8, 2006 40

-continued

40 OH

41 OH

Br

42 OH

43 OMe

45

46

C US 2006/0122243 A1 Jun. 8, 2006 41

-continued

47 OH

CC

48 OH CF

O CF

49 OH CF 3

C CF 50 OH

CF CC

51 OH CF 3

O CF CBr

52 OH CF

C o CF 53 OH CF

O CF CNO US 2006/0122243 A1 Jun. 8, 2006 42

-continued

S4 OH CF

O CF CN

55 OH CF

O CF Me

56 OH CF

d CF

Me M e Me

57 OH CF

o CF

HO

58 OH CF

O CF MeO n N Me

59 OH CF

O CF 2 a Me US 2006/0122243 A1 Jun. 8, 2006

-continued

60 OH CF

Y CF N CN

CN

61 OH CF

Y CF N CN

CO2H

62 OH CF

Y CF N CN

COMe 63 OH oCF

64 OH CF

O CF

H US 2006/0122243 A1 Jun. 8, 2006

-continued

65 OH CF

Y CF

66 OH CF

o CF

SiMe3

67 OH CF

O CF

68 OH CF

O CF

69 OH CF

C O CF US 2006/0122243 A1 Jun. 8, 2006 45

-continued

70 OH CF

O CF CCFCF

71 OH CF

O CF

72 OH CF

o CF

73 OH CF

O CF

74 OH CF

o CF

Me US 2006/0122243 A1 Jun. 8, 2006 46

-continued

75 OH CF

O CF

N

76 OH CF

O CF

77 CF

o CF OMe

78 OH CF

d CF CMe 79 OH CF

O CF Me CMe OH CF

O CF CCO2H US 2006/0122243 A1 Jun. 8, 2006 47

-continued

81 OH CF

O CF COMe

82 OH CF

CF O CF

O N CF H

83 OH CF

O CF

84 OH CF

O CF

85 OH CF

O CF

86 CF

O CF OESEO NMe2 US 2006/0122243 A1 Jun. 8, 2006 48

-continued 87 CF

O CF o==o ( ) 88 OH CF

C O CF 89 OH CF

o CF CNMe2 90 OH CF

o CF

91 OH o CF

o CF H HN r N O 92 O CF

O CF H HN r N O US 2006/0122243 A1 Jun. 8, 2006 49

-continued

93 OH CF

Y CF Nins

NO

94 OH CF

Y CF Nins

OS-N Oi? \N A 95 --O CF C CF 96 --O CF C CF C

97 OH CF

O

---,H CF US 2006/0122243 A1 Jun. 8, 2006 50

-continued

98 OH CF

C C o CF 99 OH CF

CF CC Br 100 OH CF3

C OCF 101 OH CF3

C OCF 102 OH CF

CMe OCF 103 ul CF

OCF CC 104 OH FCDO

CC US 2006/0122243 A1 Jun. 8, 2006 51

-continued

105 OH Cl

CC

106 OH CF

CBr

107 OH CF

CC

108 OH CF C F CC

109 OH CF Cl

CBr 110 OH CF

Y F CC

111 OH CF3

w Br CBr US 2006/0122243 A1 Jun. 8, 2006 52

-continued

112 OH CF

CC 113 OH CF3

CC OC 114 OH CF3

CBr O

115 OH

CC 116 OH CF3

CC ONO 117 OH CCF CBr

118 OH CF MeDC CC US 2006/0122243 A1 Jun. 8, 2006 53

-continued 119 OH CCF CC 120 OH CF3

CC OMe 121 OH CF3 C OMe CC

122 OH CF3

O OMe CBr

123 OH CF

CBr OOMe

124 OH CF3

CC OOMe 125 OH CF

CC u SMe US 2006/0122243 A1 Jun. 8, 2006 54

-continued

126 OH CF

CBr

127 OH uo.C F 3 CBr 128 OH CF

O Br CC 129 OH CF

CBr u 130 CF CF3 C NO OC 131 CF CF C CN ONO

132 CF3 CF C CN US 2006/0122243 A1 Jun. 8, 2006 55

-continued 133 C F. CF Me

OMe 134 C F. CF OMe

O OMe 135 CF CCF 136 CF3 CF3

u Me 137 CF CF3 C OMe 138 CF3 CF3

OOMe 139 OH CF3

Br OMe

140 OH CF3

Br SMe US 2006/0122243 A1 Jun. 8, 2006 56

-continued

141 OH C F3

CBr

142 OH

CC

143 OH

C

CBr 144 OH uo. CBr

145 OH C

C O C

146 OH C

C O C 147 OH C

O C CC US 2006/0122243 A1 Jun. 8, 2006 57

-continued

148 OH C

O C CBr

149 OH C

C O C 150 OH C

Br

O C cBr

151 OH C

C C O C

152 OH C

O C CNO

153 OH C

O C CMe

154 OH C

O C COMe US 2006/0122243 A1 Jun. 8, 2006 58

-continued

155 OH C

C

C CBr

156 OH C

rC CBr

157 OH F

F F

F CC F

158 OH NO

Y NO CBr

159 OH Me Me Me

CC

Me Me Me

160 OH Me Me M

CC OMe US 2006/0122243 A1 Jun. 8, 2006 59

-continued

161 OH Me

CBr

162 OH Me Me

CC

163 OH

CBr

164 OH

CC

16S OH

CC

166 OH

CC US 2006/0122243 A1 Jun. 8, 2006 60

-continued

167 OH OMe

CBr OMe 168 OH OMe

OMe CBr 169 OH

C -O-O 170 OH COMe

C COMe 171 OH H 'S N S O C C

172 C

Y C

173 OH Me Me Me

CMe

Me Me Me US 2006/0122243 A1 Jun. 8, 2006 61

-continued

174 Me ul Me Me

CC 175 OH Me Me Me

CNO Me

176 OH Me Me Me

CMe Me

177 OH Me Me Me

COMe Me

178 Me ul M Me

OMe CC 179 OH Me M Me

CMe OMe US 2006/0122243 A1 Jun. 8, 2006 62

-continued 18O OH -KN D

CBr

181 OH Me -( r Br

182 OH N -K C.

CBr

183 OH Me

-( N C

184 OH Me

-( N Br

18S OH N

—KOlS Me

Br

186 OH Me -( CBr US 2006/0122243 A1 Jun. 8, 2006 63

-continued

187 OH

Br

188 OH

Br

189 OH

Br

190 OH

CF

Br

191 OH

Br

192 OH

Br

193 OH

Me

Br US 2006/0122243 A1 Jun. 8, 2006 64

-continued

194 OH -O Me

Br

195 OH

C

196 OH

Br

197 OH

Br

198 OH

Br

199 OH

Br US 2006/0122243 A1 Jun. 8, 2006 65

-continued

200 OH

CBr

CBr

2O2 OH

CBr

2O3 OH

CBr

204 OH

CBr

205 OH

CBr US 2006/0122243 A1 Jun. 8, 2006 66

-continued

OH

Br

OH

CBr

208 OH

CBr

209 OH

CBr

210 OH

CC

211 OH

Br US 2006/0122243 A1 Jun. 8, 2006 67

-continued

212 OH

N

—{S YMe Br C O

213 OH

N

—{S NE Br C O

214 OH

N

CBr

215 OH

CBr

216 OH

CBr

217 Me Me ul (N Me O S

Me Me Me CC US 2006/0122243 A1 Jun. 8, 2006 68

-continued

218 OH O S COEt

219 OH O S COEt

F

220 OH O S COEt O F

F

221 OH O S COEt

CF

222 OH - S COEt () US 2006/0122243 A1 Jun. 8, 2006 69

-continued

223 OH -( S COEt 21 S

A No C X E

An

N Compound Number X E 301 OH 1)N1 u0

C

3O2 OH CF

O

us N N CF3 C O

303 OH O CF

us N N H O CF C

OH O us N1 N N1N H

CF C US 2006/0122243 A1 Jun. 8, 2006 70

-continued

305 OH Me CF3

ul, O CF CC O

306 OH H CF

d CF CC

307 OH O CF - 1N1 d CF CC

O CF

309 OH O CF3 YN 1. 1. CF CC

310 OH 1)N1 CF

CF CC

311 OH

N CC US 2006/0122243 A1 Jun. 8, 2006 71

-continued

312 OH 1n 1 CF3

O CF CC 313 OH 1n 1 CF3 es. O CF CC

314 OH O CF3

O CF CC

315 OH O CF3 N

d CF CC 316 OH ---O CF d CF CC

317 OH O CF N Y N d CF C 318 upy CF3 O CF CC US 2006/0122243 A1 Jun. 8, 2006 72

-continued

319 OH O CF

CF C

32O OH CF O -/ CF O

321 OH N CF 1s- N

CF C

A Yo O N N1 E H

A No

Compound Number (r E 322 OH CF C CF

323 OH CF

Me CF

324 OH CF

HO CF

Br US 2006/0122243 A1 Jun. 8, 2006 73

-continued

325 O H CF

o o CF 326 O H CF

O CF oC 327 O H CF

HO Y

O CF

328 O H CF

Me Y

o CF

329 O H CF

MeO. Y

O CF

330 OH CF

Me O CF Me

Me Me Me

331 O H CF C

C O CF oC US 2006/0122243 A1 Jun. 8, 2006 74

-continued

332 CF

O CF

Me Me Me

333 OH CF

o CF

334 CF

O CF

335 CF

o CF 336 CF

O CF

337 CF

O CF

338 CF

O CF US 2006/0122243 A1 Jun. 8, 2006 75

-continued 339 OH CF

O CF HN Me

O

340 O H CF

O CF CSONH2 341 O CF

o CF

342 OH CF

O CF

343 OH CF

Br N

o CF 344 CF 8. O CF 345 OH CF

O CF

& 3.C US 2006/0122243 A1 Jun. 8, 2006 76

-continued

346 OH CF

O Br CC 347 OH CF

O OMe CC

348 OH CF

CC C D

349 OH CF3

CC Br

350 OH CF

Y COMe CC

351 OH CF

Y YCOH CC US 2006/0122243 A1 Jun. 8, 2006 77

-continued

352 OH CF

CC OO

353 OH CF

CC O

C C

CC u N

355 OH CF3

CC OOCH2CF

356 OH CF3

CC O

MeO US 2006/0122243 A1 Jun. 8, 2006 78

-continued

357 OH CF3

CC

C

Me

358 OH CF

CC

359 OH

CC

360 OH

C

361 OH

Br US 2006/0122243 A1 Jun. 8, 2006 79

-continued

362 OH Me

CC CMe 363 OH OEt

CC OOEt

364 OH Me

CC OMe 365 OH C

CC OCN 366 OH SONEt

CC OOMe 367 OH NO

CC OC 368 OH O

CC OMe US 2006/0122243 A1 Jun. 8, 2006 80

-continued

369 OH OMe

CC OOMe

370 OH

Me

CC cOMe 371 OH OMe

CC

372 OH

CC

373 OH

CC

374 OH

C OMe US 2006/0122243 A1 Jun. 8, 2006 81

-continued

375 OH

CC

376 OH

CC

377 OH

CC

378 OH OMe

CC

379 OH C

CC

380 OH

CC C US 2006/0122243 A1 Jun. 8, 2006 82

-continued

381 OH SOMe

CC

382 OH

CC

383 OH

CC

384 OH

CC

OMe 385 OH D

CC

NO US 2006/0122243 A1 Jun. 8, 2006 83

-continued

386 OH

CC

387 OH

CC

388 OH Me

CC OH

389 OH Me

CC u OMe 390 OH

CC 391 OH

CC 392 OH Me Me

Me

C O2 H CBr

US 2006/0122243 A1 Jun. 8, 2006 85

-continued

400 OH

N

—{S N-1NM Br C O

401 OH CF

Y CF CC Me

402 OH

CC

403 OH

CC

404 OH

CC

40S OH

CC

406 OH

CC US 2006/0122243 A1 Jun. 8, 2006 86

-continued

407 OH CN

CF

CC

408 OH Br

CF

CC

409 OH Br

u CF CC

410 OH CF

u Br CC

411 OH

u CF CC 412 OH y

CF CC 413 OH CF3 OMe

CC OOMe

US 2006/0122243 A1 Jun. 8, 2006 88

-continued

421 OH

uCl N l Me H

CC 422 OH

Y CONH

CC 423 OH

Y CONHMe

CC 424 OH Me

CC Me Me

425 OH Me

CC 426 OH

Me CC 427 OH Me

Me

CC US 2006/0122243 A1 Jun. 8, 2006 89

-continued

428 OH Me

Me CC 429 OH

OCF

CC

430 OH

CC

431 OH

CC

432 OH

C

C

434 OH Me

CC

434 OH

Me -ClMe CC US 2006/0122243 A1 Jun. 8, 2006 90

-continued

435 OH

CC

436 OH Me

Me CC

437 OH uCl ->Me Me

CC

438 OH C

C CC

439 OH

CC

440 OH Br

OCF CC

441 OH

CC US 2006/0122243 A1 Jun. 8, 2006 91

-continued

442 OH

uCl Me

CC 443 OH

CC 444 OH

CC 445 OH OMe OMe

CC CN 446 OH O

COO

CC 447 OH

C

CC

C

448 OH

rC

CC US 2006/0122243 A1 Jun. 8, 2006 92

-continued

449 OH OCF Y C

CC

450 OH

CC

451 OH

CC

452 OH

CC

453 OH

CC

454 OH

CC

455 OH

Me CC US 2006/0122243 A1 Jun. 8, 2006

-continued 456 OH Ors

CC

457 OH

C -ClCN CC

458 OH Me

u CN CC

459 OH O O CC

460 OH

O

KF CC

461 OH

O -ClO F F C C F F

462 OH SCF Y C

CC US 2006/0122243 A1 Jun. 8, 2006 94

-continued

463 OH OCF

NO CC 464 OH

CC

465 OH

CC 466 OH OCF

CC

467 OH

C

468 OH

C

469 OH

C US 2006/0122243 A1 Jun. 8, 2006 95

-continued

470 OH SOMe

SOMe CC 471 OH Me O Me DCO3 C C F3 CC

472 OH

CC 473 OH C

CC r 474 OH F

Br CC 475

CC 476 OH O H

-O-O-,3 C C F 3

C C US 2006/0122243 A1 Jun. 8, 2006 96

-continued

477 OH C

CC OC

478 OH

-O-Me CC 479 OH O

CC

480 OH

CC

481 OH

CC

482 OH

CC

483 OH

CC US 2006/0122243 A1 Jun. 8, 2006 97

-continued

484 OH SCF3

CC 485 OH SOCF

CC

486 OH F

F

CC

487 OH

-Os H CC

488 OH Me

CC o 489 OH CC

CC

490 OH

O CC