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US 20060025420A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0025420 A1 Brauns et al. (43) Pub. Date: Feb. 2, 2006

(54) PHARMACEUTICAL COMPOSITIONS FOR Publication Classification THE TREATMENT OF FEMALE SEXUAL DSORDERS (51) Int. Cl. A61K 31/519 (2006.01) (75) Inventors: Ulrich Brauns, Biberach (DE); Arne A61K 31/496 (2006.01) Froemder, Ingelheim (DE); Robert (52) U.S. Cl...... 514/252.16; 514/254.06 Pyke, New Fairfield, CT (US) Correspondence Address: MICHAEL P. MORRIS BOEHRINGER INGELHEM CORPORATION (57) ABSTRACT 900 RIDGEBURY ROAD P. O. BOX 368 RIDGEFIELD, CT 06877-0368 (US) The invention relates to a method for the treatment of female (73) Assignees: Boehringer Ingelheimn International Sexual disorders comprising administration of a therapeuti GmbH, Ingelheim (DE); Boehringer cally effective amount of a compound of general formula 1 Ingelheim Pharmaceuticals, Inc., Ridgefield, CT (21) Appl. No.: 11/187,422 (22) Filed: Jul. 22, 2005 Related U.S. Application Data (60) Provisional application No. 60/592.536, filed on Jul. wherein the groupS R, L and X may have the meanings 30, 2004. Specified in the description and claims. US 2006/0025420 A1 Feb. 2, 2006

PHARMACEUTICAL COMPOSITIONS FOR THE 0006 R is -Co-Cio-aryl, optionally substituted by one TREATMENT OF FEMALE SEXUAL DISORDERS or more, preferably one group Selected from among, 0001. The invention relates to a method for the treatment -C-C-alkyl, -OH, halogen, -C(halogen), of female Sexual disorders comprising administration of a -O-C-C-alkyl, -NH2, -NH-C-C-alkyl, therapeutically effective amount of a compound of general -N(C-C-alkyl), and a nitrogen containing heteroaro formula 1 matic ring, wherein Said nitrogen containing heteroaro matic ring may optionally be Substituted by one or more, preferably one group Selected from among-C-C-alkyl, -OH, halogen, -C(halogen), and -O-C-C-alkyl, and wherein Said nitrogen containing heteroaromatic ring my optionally be linked to the -Co-Co-aryl group via a bridging group Selected from among -O-, -S-, and -NH-, or R is a group selected from among wherein the groupS R, L and X may have the meanings X X Y Specified in the description and claims. 2 2 N1 DESCRIPTION OF THE INVENTION YO,Ré /SOOC) 0002 The invention relates to a method for the treatment of female Sexual disorders comprising administration of a s^ N4 N2. therapeutically effective amount of a compound of general Y Y formula 1 Oi Oi Oil N SOY

0007) wherein 0008 X is either N or –CR-; 0009 Y is either-NR-, -O-, -S-, -SO-, -CH2- or -CO-; 0010) A is absent or a ring system selected from among wherein 0003) R' is a group selected from among halogen, -O-C-C-alkyl, and -C(halogen); OCO 0004 L is a linker, selected from the bridging groups - N-X- X. -C-C-alkylene, -C-C-alkylene-O-, -C-C- alkylene-O-CO-, -C-C-alkylene-NH-, -C-C- alkylene-NH-CO-, -C-C-alkenylene, -C-C-alk | enylene-O-, -C-C-alkenylene-O-CO-, -C-C- N N N alkenylene-NH-, -C-C-alkenylene-NH-CO-, -C-C-alkynylene, -C-C-alkynylene-O-, -C- C-alkynylene-O-CO-, -C-C-alkynylene-NH-, X. 1 QR DO and-C-C-alkynylene-NH-CO-, which may option ally be Substituted by one or more, preferably one group Selected from among -C-C-alkyl, -OH, halogen, =O, -C(halogen) and -O-C-C-alkyl, 1Oly. - N2,O 0005 R is -NH, -NHC-C-alkyl, -N(C-C- alkyl), or a group Selected from among -C-C-alkyl and -C-C-cycloalkyl which may optionally be Substi tuted by one or more, preferably one group Selected from among -C-C-alkyl, -OH, halogen, =O, -C(halo gen), -O-C-C-alkyl, -O-C-Cio-aryl, -NH2, OOOO -NHC-C-alkyl, -N(C-C-alkyl), -C-C-alkenyl 1 2. 2. and -C-C-alkynyl, or US 2006/0025420 A1 Feb. 2, 2006

tiomers or racemates thereof. In another preferred embodi -continued ment the invention relates to a method for the treatment of O O C disorderS Selected from the group consisting of Hypoactive Sexual Desire Disorder, loSS of Sexual desire, lack of Sexual desire, decreased Sexual desire, inhibited Sexual desire, comprising the administration of a therapeutically effective amount of a compound of formula 1 optionally in form of 1 x - s’ and 1 s the pharmaceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof. In another preferred 0011) B is absent or a ring system selected from among embodiment the invention relates to a method for the treatment of disorders Selected from the group consisting of Hypoactive Sexual Desire Disorder and loss of sexual desire, preferably Hypoactive Sexual Desire Disorder, com prising the administration of a therapeutically effective O)CO amount of a compound of formula 1 optionally in form of - N-X- X. the pharmaceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof. 0018. In another preferred embodiment the invention relates to a method for the treatment of premenstrual disor ders, comprising the administration of a therapeutically JDC4 R4 CO effective amount of a compound of formula 1, optionally in N form of the pharmaceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mixtures of the 1 individual enantiomers or racemates thereof. 0019. In another preferred embodiment the invention 0012) wherein the arrows indicate the positions relates to a method for the treatment of premenstrual disor where the ring is annellated to the five membered ders, Selected from the group consisting of premenstrual nitrogen heterocycle, and wherein dysphoria, premenstrual Syndrome and premenstrual dyS phoric disorder, in particular premenstrual dysphoric disor 0013 R is selected from among hydrogen, -C-C- der, comprising the administration of a therapeutically effec alkyl, CH-NH2, CH-NH-C-C-alkyl, tive amount of a compound of formula 1, optionally in form -CH-N(C-C-alkyl), -NH, -NH-C-C- of the pharmaceutically acceptable acid addition Salts, in alkyl, and form of the hydrates and/or Solvates and optionally in the 0014) -N(C-C-alkyl); form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof. 0015) R' is selected from among hydrogen, -C-C- alkyl, -OH, halogen, -C(halogen) and -O-C- 0020. In another preferred embodiment the invention C-alkyl, relates to a method for the treatment of Sexual aversion disorder in females, comprising the administration of a 0016 R is selected from among hydrogen, -C-C- therapeutically effective amount of a compound of formula alkyl, -Co-Co-aryl, and -C-C-alkylen-C-Cio 1, optionally in form of the pharmaceutically acceptable acid aryl; addition Salts, in form of the hydrates and/or Solvates and optionally in form of the pharmaceutically acceptable acid optionally in the form of the individual optical isomers, addition Salts, in form of the hydrates and/or Solvates mixtures of the individual enantiomers or racemates thereof. and optionally in the form of the individual optical 0021. In another preferred embodiment the invention isomers, mixtures of the individual enantiomers or relates to a method for the treatment of Sexual arousal racemates thereof. disorder in females, comprising the administration of a therapeutically effective amount of a compound of formula 0.017. In a preferred embodiment the invention relates to 1, optionally in form of the pharmaceutically acceptable acid a method for the treatment of female sexual disorders addition Salts, in form of the hydrates and/or Solvates and Selected from the group consisting of Hypoactive Sexual optionally in the form of the individual optical isomers, Desire Disorder, loss of Sexual desire, lack of Sexual desire, mixtures of the individual enantiomers or racemates thereof. decreased Sexual desire, inhibited Sexual desire, loss of libido, libido disturbance, and frigidity, comprising the 0022. In another preferred embodiment the invention administration of a therapeutically effective amount of a relates to a method for the treatment of orgasmic disorder in compound of formula 1 optionally in form of the pharma females, comprising the administration of a therapeutically ceutically acceptable acid addition Salts, in form of the effective amount of a compound of formula 1, optionally in hydrates and/or Solvates and optionally in the form of the form of the pharmaceutically acceptable acid addition Salts, individual optical isomers, mixtures of the individual enan in form of the hydrates and/or Solvates and optionally in the US 2006/0025420 A1 Feb. 2, 2006

form of the individual optical isomers, mixtures of the taining heteroaromatic ring Selected from among pyri individual enantiomers or racemates thereof. dine, pyrimidine, indol, pyrrole, imidazole, pyrazole, tria 0023. In another preferred embodiment the invention Zole, chinoline and isochinoline, wherein Said nitrogen relates to a method for the treatment of Sexual pain disorders containing heteroaromatic ring may optionally be Substi in females, comprising the administration of a therapeuti tuted by one or more, preferably one group Selected from cally effective amount of a compound of formula 1, option among methyl, ethyl, -OH, fluorine, chlorine, -CF, ally in form of the pharmaceutically acceptable acid addition -O-methyl and -O-ethyl, and wherein Said nitrogen Salts, in form of the hydrates and/or Solvates and optionally containing heteroaromatic ring my optionally be linked to in the form of the individual optical isomers, mixtures of the the phenyl or naphthyl group via a bridging group individual enantiomers or racemates thereof. selected from among -O- and -NH-, or 0024. In a particular preferred embodiment the invention relates to a method for the treatment Sexual pain disorders 0031) R' is a group selected from among Selected from the group consisting of dySpareunia, Vaginis mus, noncoital Sexual pain disorder, Sexual dysfunction due to a general medical condition and Substance-induced Sexual X X Y dysfunction, comprising the administration of a therapeuti cally effective amount of a compound of formula 1, option YNN (N.Y.,N s Y A : ally in form of the pharmaceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally s / in the form of the individual optical isomers, mixtures of the X X X individual enantiomers or racemates thereof. N1 N Né né ) B \ s \ B Y, and 0.025 The beneficial effects of the compositions accord Y Y ing to the invention can be observed regardless of whether the disturbance existed lifelong or was acquired, and inde pendent of etiologic origin (organic-both, physically and NYY drug induced-, psychogen, a combination of organic-both, \ B physically and drug induced-, and psychogen, or unknown). Y 0026. Another embodiment of the invention relates to the use of the compounds of formula 1, optionally in form of the pharmaceutically acceptable acid addition Salts, in form of 0032 wherein the hydrates and/or solvates and optionally in the form of the individual optical isomers, mixtures of the individual enan 0033) X is either N or -CR-; tiomers or racemates thereof for the preparation of a medi cament for the treatment of the aforementioned disorders. 0034) Y is either-NR-, -O-, or -CO-; 0027. In a preferred embodiment the invention relates to 0035 A is absent or a ring system selected from among a method for the treatment of the disorders mentioned hereinbefore, comprising administration of a therapeutically effective amount of a compound of general formula 1, wherein 0028) R' is a group selected from among fluorine, chlo OCO rine, -O-methyl, and -CF, preferably chlorine and - N-X- X. -CF; 0029 L is a linker, selected from the bridging groups -C-C-alkylene, -C-C-alkylene-O-, -C-C- alkylene-O-CO-, -C-C-alkylene-NH-, -C-C- alkylene-NH-CO-, and -C-C-alkenylene, which may optionally be Substituted by one or more, preferably one group Selected from among methyl, ethyl, propyl, J. C.R DO -OH, chlorine, fluorine, =0 and -CF; 0030) R is -NH, -NHC-C-alkyl, -N(C-C- alkyl), or a group Selected from among -C-C-alkyl Oly. O and -C-C-cycloalkyl which may optionally be Substi 1 - N2, tuted by one or more, preferably one group Selected from among -OH, fluorine, chlorine, =O, -CF, -O-phe nyl, -O-naphthyl, -NH, -NHmethyl, -N(methyl), -C-C-alkenyland-C-C-alkynyl, or R is a phenyl or naphthyl group, optionally Substituted by one or more, preferably one group Selected from among, methyl, ethyl, OOOO -OH, fluorine, chlorine, -CF, -O-methyl, -O-ethyl, 1 2. 2. -NH, -NH-methyl, -N(methyl), and a nitrogen con US 2006/0025420 A1 Feb. 2, 2006

0044) R is -NH, -NHC-C-alkyl, -N(C-C- -continued alkyl), or a group Selected from among -C-C-alkyl O O C and -C-C-cycloalkyl which may optionally be Substi tuted by one or more, preferably one group Selected from among -OH, fluorine, chlorine, =O, -CF, -O-phe nyl, -O-naphthyl, -NH, -NHmethyl, -N(methyl), -C-C-alkenyl and -C-C-alkynyl, or 1 x - s’ and 1 s 0045 R is a phenyl or naphthyl group, optionally sub Stituted by one or more, preferably one group Selected from among, methyl, ethyl, -OH, fluorine, chlorine, 0036 B is absent or a ring system selected from among -CF, -O-methyl, -O-ethyl, -NH, -NH-methyl, -N(methyl), and a nitrogen containing heteroaromatic ring Selected from among pyridine, pyrimidine, indol, pyrrole, imidazole, pyrazole, triazole, chinoline and isochinoline, wherein Said nitrogen containing heteroaro matic ring may optionally be Substituted by one or more, OCO preferably one group Selected from among methyl, ethyl, - N-X- X. -OH, fluorine, chlorine, -CF, -O-methyl and -O- ethyl, and wherein Said nitrogen containing heteroaro matic ring my optionally be linked to the phenyl or naphthyl group via a bridging group Selected from among N N N -O- and -NH-, or 0046 R is a group selected from among OG 4 QR4 DO N 1 s Co-Co 0037) wherein the arrows indicate the positions where the ring is annellated to the five membered 0047 wherein nitrogen heterocycle, and wherein 0048 X is either N or -CR-; 0038) R is selected from among hydrogen, methyl, 0049), R is selected from among hydrogen, methyl, ethyl, propyl, -CH-N(methyl), and -NGmethyl); ethyl, propyl, -CH-N(methyl), and -NGmethyl); 0039) R' is selected from among hydrogen, methyl, 0050 A is a absent or a ring system selected from ethyl, propyl, -OH, chlorine, fluorine and -CF, among 0040 R is selected from among hydrogen, methyl, ethyl, propyl, phenyl, -CH-CH2-phenyl and Ben Zyl, optionally in form of the pharmaceutically accept able acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual OOO optical isomers, mixtures of the individual enantiomers - N2 - 2. or racemates thereof. 0041. In a preferred embodiment the invention relates to a method for the treatment of the disorders mentioned N S. N. hereinbefore, comprising administration of a therapeutically effective amount of a compound of general formula 1, wherein 0042) R' is a group selected from among fluorine, chlo rine, -O-methyl, and -CF, preferably chlorine and -CF; 004.3 L is a linker, selected from the bridging groups -C-C-alkylene, -C-C-alkylene-O-, -C-C- alkylene-O-CO-, -C-C-alkylene-NH-, -C-C- alkylene-NH-CO-, and -C-C-alkenylene, which may optionally be Substituted by one or more, preferably 0051 wherein the arrows indicate the positions one group Selected from among methyl, ethyl, propyl, where the ring is annellated to the five membered -OH, chlorine, fluorine, =0 and -CF; nitrogen heterocycle, and wherein US 2006/0025420 A1 Feb. 2, 2006

0052) R' is selected from among hydrogen, methyl, ethyl, propyl, -OH, chlorine, fluorine and -CF, -continued optionally in form of the pharmaceutically acceptable s^ N4 N2* acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual \) O s \Y O s \Y O , and optical isomers, mixtures of the individual enanti omers or racemates thereof. 0053. In a preferred embodiment the invention relates to a method for the treatment of the disorders mentioned hereinbefore, comprising administration of a therapeutically effective amount of a compound of general formula 1, wherein 0061 wherein 0054) R' is a group selected from among chlorine and 0062 X is either N or -CH-; -CF, preferably -CF; 0063 Y is -O- or -CO-; 0.055 L is a linker, selected from -CH-CH-, CH-CH-CH-, -CH-CH-CH-CH-, 0064.) A is absent or a ring system selected from among O-CH-CH-, O-CH-CH-CH-, O-CH-CH-CH-CH-, -CO-O-CH CH-, -CO-O-CH-CH-CH-, -CO-O CH-CH-CH-CH-, N H-CH-CH-, NH-CH-CH-CH-, NH-CH-CH CH-CH-, CO-NH-CH-CH-, CO OCO NH-CH-CH-CH- and -CO-NH-CH - N-X- X. CH-CH-CH-, which may optionally be Substituted by one or more, preferably one group Selected from among methyl, -OH, fluorine, and -CF, 0056 R is -NH, -NHC, -C-alkyl, -N(C-C- alkyl), or a group Selected from among methyl and ethyl which may optionally be Substituted by one or more, J. C.R DO preferably one group Selected from among -OH, fluo rine, chlorine, =O, -CF, -O-phenyl, and -NH, or 0057 R is a group selected from among cyclopenty1 and cyclohexyl, which may optionally be Substituted by one 1CO - N2, or more, preferably one group Selected from among -OH, fluorine, -CF, and -C=C-, or 0.058 R is a phenyl group, optionally substituted by one or more, preferably one group Selected from among, methyl, -OH, fluorine, -CF, -NH2, and a nitrogen containing heteroaromatic ring Selected from among pyri OOOO dine, pyrimidine, indol, pyrrole, imidazole, pyrazole, tria 1 2. 2. Zole, chinoline and isochinoline, wherein Said nitrogen containing heteroaromatic ring may optionally be Substi tuted by one or more, preferably one group Selected from among methyl, -OH, fluorine, and 0059 -CF, and wherein said nitrogen containing () N R4 and heteroaromatic ring my optionally be linked to the - N-X- al e phenyl group via a bridging group Selected from among -O- and -NH-, or 0060 R is a group selected from among 0065 B is absent or a ring system selected from among Yo ?o to COOOCS. S. US 2006/0025420 A1 Feb. 2, 2006

tuted by one or more, preferably one group Selected from -continued among methyl, -OH, fluorine, and 0074 -CF, and wherein said nitrogen containing heteroaromatic ring my optionally be linked to the phenyl group via a bridging group Selected from among -O- and -NH-, or 0075), R is a group selected from among Co-Co 0.066) wherein the arrows indicate the positions where the ring is annellated to the five membered nitrogen heterocycle, and wherein 0076 wherein 0067) R' is selected from among hydrogen, methyl, 0077 X is either N or -CH-; -OH, fluorine and -CF, 0078 A is a ring system selected from among optionally in form of the pharmaceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof. N S N 0068. In a preferred embodiment the invention relates to a method for the treatment of the disorders mentioned hereinbefore, comprising administration of a therapeutically effective amount of a compound of general formula 1, wherein 0069) R' is a group selected from among chlorine and -CF, preferably -CF; 0070 L is a linker, selected from -CH-CH-, CH-CH-CH-, CH-CH-CH-CH-, O-CH-CH-, O-CH-CH-CH-, O-CH-CH-CH-CH-, CO-O-CH 0079 wherein the arrows indicate the positions CH-, -CO-O-CH-CH-CH-, -CO-O where the ring is annellated to the five membered CH-CH-CH-CH-, N H-CH-CH-, nitrogen heterocycle, and wherein NH-CH-CH-CH-, NH-CH-CH CH-CH-, CO-NH-CH-CH , CO 0080) R' is selected from among hydrogen, methyl, NH-CH-CH-CH- and -CO-NH-CH -OH, fluorine and -CF, CH-CH-CH , which may optionally be Substituted by one or more, preferably one group Selected optionally in form of the pharmaceutically acceptable acid from among methyl, -OH, fluorine, and -CF, addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical 0071) R' is -NH, -NHC-C-alkyl, -N(C-C- isomers, mixtures of the individual enantiomers or alkyl), or a group Selected from among methyl and ethyl racemates thereof. which may optionally be Substituted by one or more, preferably one group Selected from among -OH, fluo 0081. In another preferred embodiment the invention rine, chlorine, =O, -CF, -O-phenyl, and -NH, or relates to a method for the treatment of the disorders mentioned hereinbefore, comprising administration of a 0072 R is a group selected from among cyclopentyl and therapeutically effective amount of a compound of general cyclohexyl, which may optionally be Substituted by one formula 1, wherein R is or more, preferably one group Selected from among -OH, fluorine, -CF, and -C=C-, or 0082 -CF and wherein L and R have the meanings mentioned hereinbefore or below, optionally in form of 0073 R’ is a phenyl group, optionally substituted by one the pharmaceutically acceptable acid addition Salts, in or more, preferably one group Selected from among, form of the hydrates and/or Solvates and optionally in the methyl, -OH, fluorine, -CF, -NH2, and a nitrogen form of the individual optical isomers, mixtures of the containing heteroaromatic ring Selected from among pyri individual enantiomers or racemates thereof. dine, pyrimidine, indol, pyrrole, imidazole, pyrazole, tria Zole, chinoline and isochinoline, wherein Said nitrogen 0083. In another preferred embodiment the invention containing heteroaromatic ring may optionally be Substi relates to a method for the treatment of the disorders US 2006/0025420 A1 Feb. 2, 2006

mentioned hereinbefore, comprising administration of a 0093 R’ is -NH, methyl, ethyl or -CH-O-phenyl; therapeutically effective amount of a compound of general and wherein L and R' have the meanings mentioned here formula 1, wherein inbefore or below, optionally in form of the pharmaceu 0084 L is a linker, selected from -CH-CH-, tically acceptable acid addition Salts, in form of the CH-CH-CH-, -CH-CH-CH-CH-, hydrates and/or Solvates and optionally in the form of the -O-CH-CH-, -O-CH-CH-CH-, individual optical isomers, mixtures of the individual CO-O-CH-CH-, -CO-O-CH-CH enantiomers or racemates thereof. CH-, -NH-CH-CH-, -NH-CH-CH 0094. In another preferred embodiment the invention CH-, -CO-NH-CH-CH-, relates to a method for the treatment of the disorders 0085) CO-NH-CH-CH-CH and mentioned hereinbefore, comprising administration of a CO-NH-CH-CH-CH-CH-, which may therapeutically effective amount of a compound of general optionally be substituted by one or more, preferably formula 1, wherein one group Selected from among methyl, -OH, fluo 0095 R is a group selected from among cyclopentyl and rine, and -CF, cyclohexyl, which may optionally be Substituted by one and wherein R and R have the meanings mentioned or more, preferably one group Selected from among hereinbefore or below, optionally in form of the phar -OH, fluorine, -CF, and -C=C-, or maceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form and wherein L and R' have the meanings mentioned here of the individual optical isomers, mixtures of the indi inbefore or below, optionally in form of the pharmaceu vidual enantiomers or racemates thereof. tically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the 0.086. In another preferred embodiment the invention individual optical isomers, mixtures of the individual relates to a method for the treatment of the disorders enantiomers or racemates thereof. mentioned hereinbefore, comprising administration of a therapeutically effective amount of a compound of general 0096. In another preferred embodiment the invention formula 1, wherein relates to a method for the treatment of the disorders mentioned hereinbefore, comprising administration of a 0.087 L is a linker, selected from -CH-CH-, therapeutically effective amount of a compound of general CH-CH-CH-, CH-CH-CH-CH-, formula 1, wherein O-CH-CHOH-CH-, CO-O-CH CH-, -CO-NH-CH-CH-, -CO-NH 0097 R is cyclohexyl, which may optionally be substi CH-CH-CH- and -CO-NH-CH-CH tuted by one group Selected from among -OH, fluorine, CH-CH-, -CF, and -C=C-, preferably -C=C- or and wherein R and R have the meanings mentioned here and wherein L and R' have the meanings mentioned here inbefore or below, optionally in form of the pharmaceu inbefore or below, optionally in form of the pharmaceu tically acceptable acid addition Salts, in form of the tically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mixtures of the individual individual optical isomers, mixtures of the individual enantiomers or racemates thereof. enantiomers or racemates thereof. 0088. In another preferred embodiment the invention 0098. In another preferred embodiment the invention relates to a method for the treatment of the disorders relates to a method for the treatment of the disorders mentioned hereinbefore, comprising administration of a mentioned hereinbefore, comprising administration of a therapeutically effective amount of a compound of general therapeutically effective amount of a compound of general formula 1, wherein formula 1, wherein 0089 R is -NH, -NHmethyl, -N(methyl), or a 0099 R is a phenyl group, optionally substituted by one group Selected from among or more, preferably one group Selected from among, methyl, -OH, fluorine, -CF, -NH2, and a nitrogen 0090 methyl and ethyl which may optionally be sub containing heteroaromatic ring Selected from among pyri Stituted by one or more, dine, pyrimidine, indol, pyrrole, imidazole, pyrazole, tria 0091 preferably one group selected from among fluo Zole, chinoline and isochinoline, wherein Said nitrogen rine, -CF, and -O-phenyl; and wherein L and R' containing heteroaromatic ring may optionally be Substi have the meanings mentioned hereinbefore or below, tuted by one or more, preferably one group Selected from optionally in form of the pharmaceutically acceptable among methyl, -OH, fluorine, and -CF, and wherein acid addition Salts, in form of the hydrates and/or Said nitrogen containing heteroaromatic ring my option Solvates and optionally in the form of the individual ally be linked to the phenyl group via a bridging group optical isomers, mixtures of the individual enantiomers selected from among -O- and -NH-, or racemates thereof. and wherein L and R' have the meanings mentioned here 0092. In another preferred embodiment the invention inbefore or below, optionally in form of the pharmaceu relates to a method for the treatment of the disorders tically acceptable acid addition Salts, in form of the mentioned hereinbefore, comprising administration of a hydrates and/or Solvates and optionally in the form of the therapeutically effective amount of a compound of general individual optical isomers, mixtures of the individual formula 1, wherein enantiomers or racemates thereof. US 2006/0025420 A1 Feb. 2, 2006

0100. In another preferred embodiment the invention 0107 R is the group relates to a method for the treatment of the disorders mentioned hereinbefore, comprising administration of a therapeutically effective amount of a compound of general formula 1, wherein 0101 R is a phenyl group, optionally substituted by one or more, preferably one group Selected from among, methyl, -OH, fluorine, -CF and -NH, preferably NH, and wherein L and R' have the meanings mentioned here inbefore or below, optionally in form of the pharmaceu 0108) wherein tically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the 0109 X is either N or -CH-; individual optical isomers, mixtures of the individual 0110 R is selected from among hydrogen, isopropyl enantiomers or racemates thereof. and -CH2-N(methyl), preferably hydrogen or iso 0102) In another preferred embodiment the invention propyl, relates to a method for the treatment of the disorders and wherein L and R' have the meanings mentioned mentioned hereinbefore, comprising administration of a hereinbefore or below, optionally in form of the phar therapeutically effective amount of a compound of general maceutically acceptable acid addition Salts, in form of formula 1, wherein the hydrates and/or Solvates and optionally in the form 0103 R’ is a phenyl group substituted by nitrogen con of the individual optical isomers, mixtures of the indi taining heteroaromatic ring Selected from among pyri vidual enantiomers or racemates thereof. dine, pyrimidine, indol, pyrrole, imidazole, pyrazole, chi noline and isochinoline, wherein Said nitrogen containing 0111. In another preferred embodiment the invention heteroaromatic ring may optionally be Substituted by one relates to a method for the treatment of the disorders or more, preferably one group Selected from among mentioned hereinbefore, comprising administration of a methyl, -OH, fluorine, and -CF, and wherein said therapeutically effective amount of a compound of general nitrogen containing heteroaromatic ring my optionally be formula 1, wherein linked to the phenyl group via a bridging group Selected 0112 R is a group selected from among from among -O- and -NH-, and wherein L and R' have the meanings mentioned here inbefore or below, optionally in form of the pharmaceu tically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof. 0104. In another preferred embodiment the invention relates to a method for the treatment of the disorders mentioned hereinbefore, comprising administration of a therapeutically effective amount of a compound of general formula 1, wherein 0105 R is phenyl substituted via the bridging group C -NH-by a group Selected from among pyridine, pyri midine, indol, pyrrole, imidazole, pyrazole, chinoline and 2^ N isochinoline, preferably pyridine, pyrimidine, chinoline N, and isochinoline, which may optionally be Substituted by N one group Selected from among methyl, -OH, fluorine, and -CF, preferably -CF, and wherein L and R' have the meanings mentioned here 0113 wherein inbefore or below, optionally in form of the pharmaceu 0114 X is either N or -CH-, tically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the and wherein L and R' have the meanings mentioned individual optical isomers, mixtures of the individual hereinbefore or below, optionally in form of the phar enantiomers or racemates thereof. maceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form 0106. In another preferred embodiment the invention of the individual optical isomers, mixtures of the indi relates to a method for the treatment of the disorders vidual enantiomers or racemates thereof. mentioned hereinbefore, comprising administration of a therapeutically effective amount of a compound of general 0115 Preferred examples of compounds of formula 1 formula 1, wherein include US 2006/0025420 A1 Feb. 2, 2006

-continued

N OH CF, HN \ S. CF,

C S N N

and

\ { CF, N H

O HN-( CF3, CF3, \ /

optionally in form of the pharmaceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof. 0116. The alkyl groups meant here (including those which are components of other groups) are branched and unbranched alkyl groups having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as: methyl (=Me), ethyl (=Et), n-propyl, iso-propyl, butyl, iso-butyl, Sec.-butyl, tert.- butyl, pentyl, iso-pentyl, hexyl, heptyl and octyl. 0117 Unless otherwise specified alkyl groups (including those which are components of other groups) may, for example, carry one or more of the following Substituents: halogen, hydroxy, mercapto, C6-alkyloxy, amino, alky lamino, dialkylamino, cyano, nitro, =O, -CHO,-COOH, -COO-C-alkyl, -S-C1-alkyl. 0118 Alkylene groups (including those which are com ponents of other groups) are branched and unbranched bridging groups having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, Such as: methylen, ethylen, n-propylen etc. Unless otherwise specified alkylene groups (including those which are components of other groups) may, for example, carry one or more of the following Substituents: halogen, hydroxy, mercapto, C-alkyloxy, amino, alkylamino, dialkylamino, cyano, nitro, =O, -CHO, -COOH, -COO-C-alkyl, -S-C1-alkyl. 0119) Alkenyl groups (including those which are com ponents of other groups) are the branched and unbranched alkenyl groups with 2 to 6 carbon atoms, preferably 2 to 3 carbon atoms, provided that they have at least one double bond, e.g. the alkyl groups mentioned above provided that US 2006/0025420 A1 Feb. 2, 2006

they have at least one double bond, Such as for example 0128. The compounds of formula 1 are capable of form vinyl (provided that no unstable enamines or enolethers are ing acid addition Salts with pharmaceutically acceptable formed), propenyl, iso-propenyl, butenyl, pentenyl and hex acids. Representative pharmaceutically acceptable acid enyl. addition Salts include the following: Acetate, Benzene 0120 Unless otherwise specified, alkenyl groups, Sulfonate, Benzoate, Bicarbonate, Bisulfate, Bitartrate, (including those which are components of other groups), Borate, Bromide, Camsylate, Carbonate, Chloride, Clavu may for example carry one or more of the following Sub lanate, Citrate, Dihydrochloride, Edetate, Edisylate, Esto Stituents: halogen, hydroxy, mercapto, C-alkyloxy, amino, late, Esylate, Fumarate, Gluceptate, Gluconate, Glutamate, alkylamino, dialkylamino, cyano, nitro, =O, -CHO, GlycolylarSanilate, HeXylresorcinate, Hydrabamine, -COOH, -COO-C-alkyl, -S-C1-alkyl. Hydrobromide, Hydrochloride, Hydroxynaphthoate, Iodide, Isothionate, Lactate, Lactobionate, Laurate, Malate, Male 0121 Alkenylene groups (including those which are ate, Mandelate, Mesylate, Methylbromide, Methylnitrate, components of other groups) are the branched and Methylsulfate, Mucate, Napsylate, Nitrate, N-methylglu unbranched bridging groups with 2 to 6 carbon atoms, camine ammonium Salt, Oleate, Oxalate, Pamoate preferably 2 to 3 carbon atoms, provided that they have at (Embonate), Palmitate, Pantothenate, Phosphate/diphos least one double bond, e.g. the alkylene groups mentioned phate, Polygalacturonate, Salicylate, Stearate, Sulfate, Sub above provided that they have at least one double bond, such acetate, Succinate, Tannate, Tartrate, Teoclate, Tosylate, as for example vinylene, propenylene, etc. Triethiodide and Valerate. 0.122 Unless otherwise specified, alkenylene groups, 0129. The compounds of formula 1 including methods (including those which are components of other groups), for the preparation thereof are known in the art. They can be may for example carry one or more of the following Sub obtained for instance according to the methods described in Stituents: halogen, hydroxy, mercapto, C-alkyloxy, amino, WO 03/011396 or in analogy to the methods disclosed alkylamino, dialkylamino, cyano, nitro, =O, -CHO, therein. -COOH, -COO-C-alkyl, -S-C1-alkyl. 0123 The term alkynyl groups (including those which 0.130. The term “therapeutically effective amount” shall are components of other groups) refers to alkynyl groups mean that amount of a drug or pharmaceutical agent that will having 2 to 6 carbon atoms provided that they have at least elicit the biological or medical response of a human that is one triple bond, e.g. ethynyl, propargyl, butynyl, pentynyl being Sought by a researcher or clinician. and hexynyl. Unless otherwise Specified, alkynyl groups, 0131 The compounds 1 may have chiral centers and (including those which are components of other groups), occur as racemates, racemic mixtures and as individual may for example carry one or more of the following Sub diastereomers, or enantiomers with all isomeric forms being Stituents: halogen, hydroxy, mercapto, C-alkyloxy, amino, included in the present invention. Therefore, where a com alkylamino, dialkylamino, cyano, nitro, =O, -CHO, pound is chiral, the Separate enantiomers, Substantially free -COOH, -COO-C-alkyl, -S-C1-alkyl. of the other, are included within the scope of the invention. 0124. The term alkynylene groups (including those Further included are all mixtures of the two enantiomers. which are components of other groups) refers to bridging Also included within the Scope of the invention are poly groups having 2 to 6 carbon atoms provided that they have morphs and hydrates of the compounds of the instant at least one triple bond, e.g. ethynylene, propargylene, etc. invention. Unless otherwise specified, alkynylene groups, (including 0.132. Furthermore, the invention relates to new pharma those which are components of other groups), may for ceutical compositions for the treatment of the disorders example carry one or more of the following Substituents: Specified hereinbefore comprising a compound of formula 1. halogen, hydroxy, mercapto, C6-alkyloxy, amino, alky The pharmaceutical compositions comprising a compound lamino, dialkylamino, cyano, nitro, =O, -CHO,-COOH, of formula 1 may be administered by oral, parenteral (e.g., -COO-C-alkyl, -S-C1-alkyl. intramuscular, intraperitoneal, intravenous or Subcutaneous 0.125 Examples of cycloalkyl groups having 3 to 6 injection, or implant), buccal, nasal, vaginal, rectal, Sublin carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl gual, or topical (e.a. ocular eyedrop) routes of administration and cyclohexyl, which may also be substituted by branched and may be formulated, alone or together, in Suitable dosage or unbranched C-alkyl, hydroxy and/or halogen or as unit formulations containing conventional non-toxic phar hereinbefore defined. The term halogen generally refers to maceutically acceptable carriers, adjuvants and Vehicles fluorine, chlorine, bromine or iodine. appropriate for each route of administration. 0.126 The word aryl denotes an aromatic ring system 0133. The pharmaceutical compositions for the adminis having 6 to 10 carbon atoms which, unless otherwise Speci tration of the compounds of formula 1 of this invention may fied, may carry one or more of the following Substituents, for conveniently be presented in dosage unit form and example: Co-alkyl, C-alkyloxy, halogen, hydroxy, mer 0134) may be prepared by any of the methods well known capto, amino, alkylamino, dialkylamino, CF, cyano, nitro, in the art of pharmacy. All methods include the Step of -CHO,-COOH, -COO-C-alkyl, -S-C1-alkyl. bringing the active ingredient into association with the The preferred aryl group is phenyl. carrier which is constituted of one or more accessory ingre 0127 =O denotes a double bonded oxygen atom. The dients. In general, the pharmaceutical compositions are term -CO-, mostly part of another group, Specifies a prepared by uniformly and intimately bringing the active carbonyl group. The term annellated ring is to be understood ingredients into association with a liquid carrier or a finely as a ring being fused to another ring fragment via two divided Solid carrier or both, and then, if necessary, Shaping common carbon centers. the product into the desired dosage form. In the pharmaceu US 2006/0025420 A1 Feb. 2, 2006 tical compositions the active compounds are included in an polyoxyethylene Stearate, (b.3) a condensation product of amount Sufficient to produce the desired pharmacologic ethylene oxide with a long chain aliphatic , for effect. example 0135 The pharmaceutical compositions containing the 0.142 heptadecaethyleneoxycetanol, (b.4) a condensation compounds of formula 1 that are Suitable for oral adminis product of ethylene oxide with a partial ester derived from tration may be in the form of discrete units Such as hard or a fatty acid and a hexitol Such as polyoxyethylene Sorbitol Soft capsules, tablets, troches or lozenges, each containing a monooleate, or (b.5) a condensation product of ethylene predetermined amount of the active ingredients, in the form oxide with a partial ester derived from a fatty acid and a of a dispersible powder or granules, in the form of a Solution hexitol anhydride, for example polyoxyethylene Sorbitan or a Suspension in an aqueous liquid or non-aqueous liquid; monooleate. in the form of syrups or elixirs, or in the form of an 0143. The aqueous Suspensions may also contain one or oil-in-water emulsion or a water-in-oil emulsion. more preservatives, for example, ethyl or n-propyl p-hy 0.136 Dosage forms intended for oral use may be pre droxybenzoate, one or more coloring agents, one or more pared according to any method known to the art for the flavoring agents, and one or more Sweetening agents, Such manufacture of pharmaceutical formulations and Such com as Sucrose or Saccharin. positions. 0144. Oily suspensions may be formulated by Suspending 0137 The excipients used may be for example, (a) inert the compounds of formula 1 in a vegetable oil, for example diluents Such as mannitol, Sorbitol, calcium carbonate, arachis oil, olive oil, Sesame oil or coconut oil, or in a pregelatinized Starch, lactose, calcium phosphate or Sodium mineral oil Such as liquid paraffin. The oily Suspensions may phosphate; (b) granulating and disintegrating agents, Such as contain a thickening agent, for example beeswax, hard poVidone, copoVidone, hydroxypropylmethylcellulose, corn paraffin or cetyl alcohol. Sweetening agents and flavoring Starch, alginic acid, croSpoVidone, Sodiumstarchglycolate, agents may be added to provide a palatable oral preparation. croScarmellose, or polacrilin potassium; (c) binding agents These compositions may be prepared by the addition of an Such as microcrystalline cellulose or acacia, and (d) lubri antioxidant Such as ascorbic acid. cating agents Such as magnesium Stearate, Stearic acid, fumaric acid or talc. 0145 Dispersible powders and granules are suitable for the preparation of an aqueous Suspension. They provide the 0.138. In some cases, formulations for oral use may be in compounds of formula 1 in admixture with a dispersing or the form of hardgelatin or HPMC capsules wherein the Wetting agent, a Suspending agent and one or more preser active ingredient compound of formula 1 is mixed with an Vatives. Suitable dispersing or wetting agents and Suspend inert Solid diluent, for example pregelatinized Starch, cal ing agents are exemplified by those already mentioned cium carbonate, calcium phosphate or kaolin, or dispensed above. Additional excipients, for example, those Sweeten via a pellet formulation. They may also be in the form of soft ing, flavoring and coloring agents described above may also gelatin capsules wherein the active ingredient is mixed with be present. water or an oil medium, for example peanut oil, liquid paraffin, medium chain triglycerides or olive oil. 0146 The pharmaceutical compositions of the invention may also be in the form of oil-in-water emulsions. The oily 0.139. The tablets, capsules or pellets may be uncoated or phase may be a vegetable oil Such as olive oil or arachis oils, they may be coated by known techniques to delay disinte or a mineral oil Such as liquid paraffin or a mixture thereof. gration and absorption in the gastrointestinal tract and thereby provide a delayed action or Sustained action over a 0147 Suitable emulsifying agents may be (a) naturally longer period. For example, a time delay material Such as occurring gums. Such as gum acacia and gum tragacanth, (b) celluloseacetate phtalate or hydroxypropylcellulose acetate naturally-occurring phosphatides Such as Soybean and leci Succinate or Sustained release material Such as ethylcellulose thin, (c) esters or partial esters derived from fatty acids and or ammoniomethacrylate copolymer (type B) may be hexitol anhydrides, for example, Sorbitan monooleate, (d) employed. condensation products of Said partial esters with ethylene oxide, for example polyoxyethylene Sorbitan monooleate. 0140 Liquid dosage forms for oral administration The emulsions may also contain Sweetening and flavoring include pharmaceutically acceptable emulsions, Solutions, agents. Suspensions, Syrups, and elixirs containing inert diluents commonly used in the art, Such as water. Besides Such inert 0.148 Syrups and elixirs may be formulated with Sweet diluents, compositions can also include adjuvants, Such as ening agents, for example, glycerol, propylene glycol, Sor Wetting agents, emulsifying and Suspending agents, and bitol or Sucrose. Such formulations may also contain a Sweetening, flavoring, perfuming and preserving agents. preservative and flavoring and coloring agents. 0141 Aqueous Suspensions normally contain the com 014.9 The pharmaceutical compositions containing com pounds of formula 1 in admixture with excipients Suitable pounds of formula 1 may be in the form of a sterile injectable for the manufacture of aqueous Suspensions. Such excipients aqueous or oleagenous Suspension or Solution. The Suspen may be (a) Suspending agents Such as hydroxy ethylcellu Sion may be formulated according to known methods using lose, Sodium carboxymethylcellulose, methylcellulose, those Suitable dispersing or wetting agents and Suspending hydroxypropylmethylcellulose, Sodium alginate, polyvi agents which have been mentioned above. The Sterile inject nylpyrrolidone, gum tragacanth and gum acacia; (b) dispers able preparation may also be a sterile injectable Solution or ing or wetting agents which may be (b. 1) a naturally Suspension in a non toxic parenterally-acceptable diluent or occurring phosphatide Such as lecithin, (b.2) a condensation Solvent, for example as a Solution in 1,3-butane-diol. Among product of an alkylene oxide with a fatty acid, for example, the acceptable vehicles and Solvents that may be employed US 2006/0025420 A1 Feb. 2, 2006

are water, Ringer's Solution and isotonic Sodium chloride one active ingredient Selected from the group consisting of Solution. In addition, Sterile, fixed oils are conventionally melanocortin , prostaglandin E1 agonists, elevators employed as a Solvent or Suspending medium. For this of cyclic guanosine 3',5'-monophosphate (cGMP) (prefer purpose any bland fixed oil may be employed including ably PDE V inhibitors), 5-HT-1A agonists, ago Synthetic mono-or diglycerides. In addition, fatty acids Such nists, dopamine D4 antagonist and 5-HT2A/C antagonists. as oleic acid find use in the preparation of injectables. 0156 The compositions according to the invention may 0150 Preparations according to this invention containing contain 1 and the one or more additional active ingredient in compounds of formula 1 for parenteral administration a single formulation or in Separate formulations. If 1 and the include Sterile aqueous or non-aqueous Solutions, Suspen one or more additional active ingredient are present in Sion, or emulsions. Separate formulations these Separate formulations may be administered simultaneously or Sequentially. 0151 Examples of non-aqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, Such O157. A preferred embodiment according to the invention as olive oil and corn oil, gelatin, and injectable organic esters is directed to pharmaceutical compositions comprising a Such as ethyl oleate. Such dosage forms may also contain therapeutically effective amount of 1 and a therapeutically adjuvants Such as preserving, wetting, emulsifying, and effective amount of one or more, preferably one melanocor dispersing agents. They may be Sterilized by, for example, tin , optionally in combination with a pharmaceuti filtration through a bacteria-retaining filter, by incorporating cally acceptable excipient. Sterilizing agents into the compositions, by irradiating the 0158 Examples of Suitable melanocortin agonists compositions, or by heating the compositions. They can also include PT-141, MCL-0129, PG-917, and Ro-27-3225, be manufactured in the form of Sterile Solid compositions optionally in form of the pharmaceutically acceptable acid which can be reconstituted in Sterile water, or Some other addition Salts, in form of the hydrates and/or Solvates and Sterile injectable medium immediately before use. The com optionally in the form of the individual optical isomers, bination of this invention may also be administered in the mixtures of the individual enantiomers or racemates thereof. form of Suppositories for rectal administration. This com position can be prepared by mixing the drugs with a Suitable 0159. Another preferred embodiment according to the non-irritating excipient which is Solid at ordinary tempera invention is directed to pharmaceutical compositions com tures but liquid at the rectal temperature and will therefore prising a therapeutically effective amount of 1 and a thera melt in the rectum to release the drug. Such materials are peutically effective amount of one or more, preferably one cocoa butter, hard fat, and polyethylene glycols. Composi prostaglandin E1 agonist, optionally in combination with a tions for buccal, nasal or Sublingual administration are also pharmaceutically acceptable excipient. Examples of Suitable prepared with Standard excipients well known in the art. prostaglandin E1 agonists, include ornoprostil, limaprost, alproStadil, gemeprost, liprostin, NMI-775, prostaglandin E 0152 For topical administration the combinations of this (PGE-1), papaverine, dioxyline, ethaverine, phentolamine, invention containing compounds of formula 1 may be for , minoxidil, nitroglycerin, alpha blockers, nitric mulated in liquid or Semi-liquid preparations Such as lini oxide donors, and peptides (e.g., VIP), from which orno ments, lotions, applications, oil-in-water or water-in-oil prostil, limaprost and alprostadil are particularly preferred emulsions Such as creams, ointments, jellies or pastes, optionally in form of the pharmaceutically acceptable Salts, including tooth-pastes, or Solutions or Suspensions Such as in form of the hydrates and/or Solvates and optionally in the drops, and the like. form of the individual optical isomers, mixtures of the 0153. The dosage of the active ingredients in the com individual enantiomers or racemates thereof. positions of this invention may be varied. However, it is 0160 Another preferred embodiment according to the necessary that the amount of the compounds of formula 1 be invention is directed to pharmaceutical compositions com Such that a Suitable dosage form is obtained. The Selected prising a therapeutically effective amount of 1 and a thera dosage and the dosage form depend upon the desired thera peutically effective amount of one or more, preferably one peutic effect, on the route of administration and on the elevator of c(GMP, preferably a coMP phosphodiesterase duration of the treatment. Dosage ranges in the combination (cGMP PDE) inhibitor, more preferably a selective PDE V are approximately one tenth to one times the clinically inhibitor, optionally in combination with a pharmaceutically effective ranges required to induce the desired therapeutic acceptable excipient. Examples of elevators of c(GMP, in effect, respectively when the compounds are used Singly. particular examples for Suitable PDE V inhibitors include Within the instant invention compounds of formula 1 are , , , NCX-911, Sch-444877, preferably administered in Such an amount that per Single FR-229934, 4-bromo-5-(pyridylmethylamino)-6-3-(4-chlo dosage between 0.001 to 1000 mg of 1 are applied. rophnyl)-propoxy-3 (2H)pyridazinone, 1-4-(1,3-benzo dioxol-5-ylmethyl)amiono-6-chloro-2-quinozolinyl-4-pi 0154) In another embodiment, the instant invention is peridine-carboxylic acid, monosodium salt, (+)-cis-5,6a,7, directed to pharmaceutical compositions comprising a thera 9,9.9a-hexahydro-2-4-(trifluoromethyl)-phenylmethyl-5- peutically effective amount of a compound of formula 1 in methyl-cyclopent-4.5imidazo2,1-bpurin-4 (3H)one, combination with a therapeutically effective amount of furaziocillin, cis-2-hexyl-5-methyl-3,4,5,6a,7,8,9,9a-oc another active ingredient for the treatment of the disorders tahydrocyclopent4.5-imidazo[2,1-bpurin-4-one, 3-acetyl mentioned hereinbefore. 1-(2-chlorobenzyl)-2 propylindole-6-carboxylate, 3-acetyl 0.155) A preferred embodiment of the invention is 1-(2-chlorobenzyl)-2-propylindole-6-carboxylate, 4-bromo directed to pharmaceutical compositions comprising a thera 5-(3-pyridyl methylamino)-6-(3-(4-chlorophenyl) propoxy)- peutically effective amount of 1 in combination with a 3-(2H)pyridazinone, 1-methyl-5(5-morpholinoacetyl-2-n- therapeutically effective amount of one or more, preferably propoxyphenyl)-3-n-propyl-1,6-dihydro-7H-pyrazolo(4,3- US 2006/0025420 A1 Feb. 2, 2006

d)pyrimidin-7-one, 1-4-(1,3-benzodioxol-5- EMD-67478, EMD-77697, , , BP-554, ylmethyl)amino-6-chloro-2-quinazolinyl-4- CGP-50281, CGS-12066B, CGS-18102, SDZ-MAR-327, piperidinecarboxylic acid, monosodium salt, GF-196960, CL-870801, CP-110330, CP-146662, CP-291952, FCE E-8010, E-4010, Bay-38-3045, Bay-38-9456, FR226807, 23892, FG-5865, FG-5893, OSU-191, , Sch-51866, 5-(2-ethoxy-5-morpholinoacetylphenyl)-1-me U-67413B, U-86170, U-86192A, U-92016A, U-93385, thyl-3-n-propyl-1,6-dihydro-7H-pyrazolo 4,3-dipyrimidin , Mazapertine succinate, SL-870765, SL-880338, 7-one, 3-ethyl-5-5-(4-ethylpiperazin-1-ylsulfonyl)-2-n-pro SR-59026, , , S-14506, S-14671, poxyphenyl-2-(pyridin-2-yl)methyl-2,6-dihydro-7H S-15535, S-15931, S-16924, S-213571, S-215521, Elopipra pyrazolo 4,3-dpyrimidin-7-one, 3-ethyl-5-5-(4- zole, , , , SUN-8399, ethylpiperazin-1-ylsulfonyl)-2-(2methoxyethoxy)pyridin-3- S-23751, PM-1000, LY 41, , WY-48723, yl)-2-(pyridin-2-yl)methyl-2,6-dihydro-7H-pyrazolo 4,3-d and MDL-73975, optionally in form of the pyrimidin-7-one, (+)-3-ethyl-5-5-(4-ethylpieperazin-1- pharmaceutically acceptable acid addition Salts, in form of ylsulfonyl)-2-(2-methoxy-1 (R)-methylethoxy)pyridin-3- the hydrates and/or Solvates and optionally in the form of the yl)-2-methyl-2,6-dihydro-7H-pyrazolo 4,3-dpyrimidin-7- individual optical isomers, mixtures of the individual enan one, 5-2-ethoxy-5-(4-ethylpiperazin-1-ylsulfonyl)pyridin tiomers or racemates thereof. 3-yl)-3-ethyl-2-2-methoxyethyl-2,6-dihydro-7H-pyrazolo 4,3-dpyrimidin-7-one, 5-2-iso-butoxy-5-(4- 0.164 Preferred examples of Suitable 5-HT1A agonists ethylpiperazin-1-ylsulfonyl)pyridin-3-yl)-3-ethyl-2-(1- include , , , , Naf methylpiperidin-4-yl)-2,6-dihydro-7H-pyrazolo 4,3-d topidil, , , , , pyrimidin-7-one, Sumanirole, hydrochloride, , AP-521, SUN-N4057, , MKC-242, OPC-14523, 0161 5-2-ethoxy-5-(4-ethylpiperazin-1-ylsulfonyl)pyri Eptapirone maleate, SLV-308, BTS-79018, R-137696, din-3-yl)-3-ethyl-2-phenyl-2,6-dihydro-7H-pyrazolo 4,3- F-13640, SSR-181507, SLV-314, SLV-319, 7-OH-DPAT, dpyrimidin-7-one, 5-(5-Acetyl-2-propoxy-3-pyridinyl)- VN-2222, PD-158771, RS-30199 and WAY-100012, option 3-ethyl-2-(1-isopropyl-3-azetidinyl)-2,6-dihydro-7H ally in form of the pharmaceutically acceptable acid addition pyrazolo 4,3-dipyrimidin-7-one, 5-(5-Acetyl-2-butoxy Salts, in form of the hydrates and/or Solvates and optionally 3-pyridinyl)-3-ethyl-2-(1-ethyl-3-azetidinyl)-2,6- in the form of the individual optical isomers, mixtures of the dihydro-7H-pyrazolo 4,3-dipyrimidin-7-one, 4-(4- individual enantiomers or racemates thereof. chlorobenzyl)amino-6,7,8-trimethoxyquinazoline, 0.165 Another preferred embodiment according to the 0162 7,8-dihydro-8-oxo-6-2-propoxyphenyl)-1H-imi invention is directed to pharmaceutical compositions com dazo4.5-gquinazoline, 1-3-1-(4-fluorophenyl)m- prising a therapeutically effective amount of 1 and a thera ethyl-7,8-dihydro-8-oxo-1H-imidazo[4,5-gquinazolin peutically effective amount of one or more, preferably one 6-yl)-4-propoxyphenylcarboxamide, 2-2-ethoxy-5-(4- dopamine agonist, optionally in combination with a phar ethyl--1-Sulfonyl)-phenyl-5-methyl-7-propyl maceutically acceptable excipient. 3H-imidazo5,1-f-1,2,4-triazin-4-one, and 1-6- 0166 Examples of suitable dopamine agonists include ethoxy-5-3-ethyl-6,7-dihydro-2-(2-methoxyethyl)-7- ABT-724, CP-226269, bromocriptin, cabergolin, alpha-di oxo-2H-pyrazolo 4,3-dipyrimidin-5-yl)-3- hydroergocryptin, , , pramipexol, roXindol, pyridylsulfonyl)-4-ethylpiperazine, optionally in form of ropinirol, Sopirinol, talipexol, and the pharmaceutically acceptable acid addition Salts, in optionally in form of the pharmaceutically acceptable acid form of the hydrates and/or Solvates and optionally in the addition Salts, in form of the hydrates and/or Solvates and form of the individual optical isomers, mixtures of the optionally in the form of the individual optical isomers, individual enantiomers or racemates thereof. mixtures of the individual enantiomers or racemates thereof. 0163 Another preferred embodiment according to the invention is directed to pharmaceutical compositions com 0.167 Preferred examples of suitable dopamine agonist prising a therapeutically effective amount of 1 and a thera include pramipexol, bupropion roXindol, and talipexol, peutically effective amount of one or more, preferably one optionally in form of the pharmaceutically acceptable acid 5-HT-1A agonist, optionally in combination with a pharma addition Salts, in form of the hydrates and/or Solvates and ceutically acceptable excipient. Examples of Suitable 5-HT optionally in the form of the individual optical isomers, 1A agonists include Urapidil, Buspirone, Aripiprazole, mixtures of the individual enantiomers or racemates thereof. Ziprasidone, , TandoSpirone, Nemonapride, 0168 Another preferred embodiment according to the Gepirone, Repinotan, Sumanirole, Xaliproden hydrochlo invention is directed to pharmaceutical compositions com ride, BifeprunoX, AP-521, SUN-N4057, Sarizotan, MKC prising a therapeutically effective amount of 1 and a thera 242, OPC-14523, Eptapirone maleate, SLV-308, BTS peutically effective amount of one or more, preferably one 79018, R-137696, F-13640, SSR-181507, SLV-314, SLV 5-HT2A/ antagonist, optionally in combination with a 319, 7-OH-DPAT, VN-2222, PD-158771, RS-30199, WAY pharmaceutically acceptable excipient. Examples of Suitable 100012, A-74283, , Org-13011, B-8805-033, 5-HT2A/2C antagonists include Aripiprazole, , AP-159, AZ-16596, Anpirtoline, , , , , , , Ziprasi MDL-72832, RU-24969, Bay-r-1531, , BIMG 80, done, , , , , BMS-181100, BMS-181101, BMS-181970, BMY-7378, , , M 100907, Netamiftide, , BW-1205U90, B-20991, HAT-90B, Nerisopam, LY-175644, S-20098, Abaperidone, ACP-103, EMR 62218, LU-31-130, LY-178210, LY-228729, LY-274600, LY-274601, SL 650472, EGIS-10037, LEK-8829, , LY-293284, LY-301317, LY-315535, E-4414, E-6265 citrate, QF-2004B, R-107500, S 35120, S-14297, , , RGH-1756, RGH-1757, 1192U90, HP-236, , AT 1015, Balaperidone, BIMG 80, Deramci FG-5938, LEK-8804, LB-50016, RWJ-25730, EMD-56551, clane, EGIS 8465, EGIS 9933, , FG 5803, FG US 2006/0025420 A1 Feb. 2, 2006

5893, FG-5938, FG-5974, GMC 1169, GMC 283, GMC What is claimed is: 306, GMC 6139, ICI-169369, Irindalone, IT 657, JL-13, 1) A method for the treatment of female sexual disorders , LY 215840, LY-367265, NRA-0045, Org comprising administration of therapeutically effective 38457, PNU-96415E, OF 0510B, QF 1003B, QF 1004B, amount of a compound of formula 1 RO 600946, Ro-60-0759, RP 71602, RS-102221, S 16924, S 213571, S35031, S-17828, S-21357-1, SB 200646A, SB 206553, SB 221284, SB 228357, SB 242084, SB 243213, SDZ SER 082, TY 12283, TY-11223 and ZD-3638 option ally in form of the pharmaceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof.

0169 Preferred 5-HT2A/2C antagonist include Aripipra wherein zole, Fluoxetine, Nefazodone, Pizotifen, Risperidone, Sar pogrelate, Ziprasidone, Agomelatine, ASenapine, Eplivan R" is a group selected from among halogen, -O-C- serin, Iloperidone, M 100907, Netamiftide, Ocaperidone, C-alkyl, and -C(halogen); S-20098, Abaperidone, ketanserin, ritanserin, ACP-103, L is a linker, Selected from the bridging groups -C-C- EMR 62218, LU-31-130, SL 650472, EGIS-10037, LEK alkylene, -C-C-alkylene-O-, -C-C-alkylene 8829, Nantenine, QF-2004B, R-107500, S 35120 and O-CO-, -C-C-alkylene-N H-, -C-C-alky S-14297 optionally in form of the pharmaceutically accept lene-NH-CO-, -C-C-alkenylene, -C-C- able acid addition Salts, in form of the hydrates and/or alkenylene-O-, -C-C-alkenylene-O-CO-, Solvates and optionally in the form of the individual optical -C-C-alkenylene-NH-, -C-C-alkenylene isomers, mixtures of the individual enantiomers or race NH-CO-, -C-C-alkynylene, -C-C-alky mates thereof. Particular preferred 5-HT2A/2C antagonist nylene-O-, -C-C-alkynylene-O-CO-, -C- are Selected from among Aripiprazole, Fluoxetine, Nefaz C-alkynylene-N H-, and odone, Pizotifen, Risperidone, Sarpogrelate and Ziprasidone optionally in form of the pharmaceutically acceptable acid -C-C-alkynylene-NH-CO-, which may option addition Salts, in form of the hydrates and/or Solvates and ally be substituted by one or more, preferably one optionally in the form of the individual optical isomers, group Selected from among -C-C-alkyl, -OH, halogen, =O, -C(halogen) and -O-C-C- mixtures of the individual enantiomers or racemates thereof. alkyl, 0170 Another preferred embodiment according to the invention is directed to pharmaceutical compositions com R’ is -NH, -NHC-C-alkyl, -N(C-C-alkyl), or a prising a therapeutically effective amount of 1 and a thera group Selected from among -C-C-alkyl and -C- peutically effective amount of one or more, preferably one C-cycloalkyl which may optionally be substituted by dopamine D4 antagonist, optionally in combination with a one or more, preferably one group Selected from among pharmaceutically acceptable excipient. Examples of Suitable -C-C-alkyl, -OH, halogen, =O, -C(halogen), dopamine D4 antagonists include , Ziprasidone, -O-C-C-alkyl, -O-C-C-aryl, -NH2, MDL-814608A, NRA-0562, S-18126, SPI-376, YM-50001, -NHC-C-alkyl, -N(C-C-alkyl), -C-C-alk 1192U90, ALX-D4, Balaperidone, BIMG 80, Coso, enyl and -C-C-alkynyl, or CP-293019, Fananserin, JL-13, L-741742, L-745870, R is -Co-Cio-aryl, optionally Substituted by one or L-751852, L-772620, L-800892, LU-35138, LUR-2366, more, preferably one group Selected from among, NEO-376, NGB-4420, NGD-941, NRA-0045, NRA-0074, -C-C-alkyl, -OH, halogen, -C(halogen), NRA-0154, NRA-0160, NRA-0161, NRA-0215, NRA -O-C-C-alkyl, -NH, -NH-C-C-alkyl, 0219, NRA-0544, PD-089232, PD-108306, PD-165167, -N(C-C-alkyl), and a nitrogen containing het PD-167063, PD-168306, PD-172760, PD-172760, eroaromatic ring, wherein Said nitrogen containing PD-172938, PD-35680, PD-82011, PNU-106161, PNU heteroaromatic ring may optionally be Substituted by 106675, QF-1003B, OF-1004B, Ro-62-4599, S-16924, one or more, preferably one group Selected from among S-17828, Sch-71450, , U-101958, -C-C-alkyl, -OH, halogen, -C(halogen), and U-103073E, U-96415E and YM-43611, optionally in form -O-C-C-alkyl, and wherein Said nitrogen contain of the pharmaceutically acceptable acid addition Salts, in ing heteroaromatic ring my optionally be linked to the form of the hydrates and/or Solvates and optionally in the -C-Cio-aryl group via a bridging group Selected from form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof. among -O-, -S-, and -NH-, or 0171 Preferred examples of suitable dopamine D4 R is a group selected from among antagonist include olanzapine, Ziprasidone, MDL-814608A, NRA-0562, S-18126, SPI-376 and YM-50001, in particular olanzapine and Ziprasidone, optionally in form of the phar maceutically acceptable acid addition Salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mixtures of the individual enan Yo ?o to tiomers or racemates thereof. US 2006/0025420 A1 Feb. 2, 2006

-continued -continued s^ N4 N2 Y Y

wherein X is either N or -CR-; rein the arrows indicate the positions where the ring is annellated to the five membered nitrogen heterocycle, Y is either-NR-,-O-, -S-, -SO-, -CH and wherein or -CO-, R is selected from among hydrogen, -C-C-alkyl, A is absent or a ring System Selected from among -CH-NH, -CH-NH-C-C-alkyl, -CH N(C-C-alkyl), -NH, -NH-C-C-alkyl, and -N(C-C-alkyl); R" is selected from among hydrogen, -C-C-alkyl, -OH, halogen, -C(halogen) and -O-C-C-alkyl, O)CO R is selected from among hydrogen, -C-C-alkyl, - N-X- X. -C-C-aryl, and -C-C-alkylen-C-C-aryl; a pharmaceutically acceptable acid addition Salt thereof, a hydrate or Solvate thereof, or in the form of the indi vidual optical isomer, mixture of the individual enan N N N tiomers or a racemate thereof. 2) The method for the treatment of female sexual disor derS according to claim 1, wherein the disorder is Selected OG Q DO from the group consisting of Hypoactive Sexual Desire Disorder, loSS of Sexual desire, lack of Sexual desire, decreased Sexual desire, inhibited Sexual desire, loss of libido, libido disturbance, and frigidity. 1CO - N2, 3) The method for the treatment of female sexual disor derS according to claim 1, wherein the disorder is Selected from premenstrual disorders. 4) The method for the treatment of female sexual disor derS according to claim 1, wherein the disorder is Sexual aversion disorder. 5) The method for the treatment of female sexual disor OOOO4 derS according to claim 1, wherein the disorder is Sexual 1 2. 2. s arousal disorder. 6) The method for the treatment of female sexual disor derS according to claim 1, wherein the disorder is orgasmic disorder. N N N C 7) The method for the treatment of female sexual disor derS according to claim 1, wherein the disorder is a Sexual 1 X. 1 e and e pain disorder. 8) The method for the treatment of female sexual disor derS according to claim 1, comprising administration of a therapeutically effective amount of a compound of formula B is absent or a ring System Selected from among 1, wherein R" is a group selected from among fluorine, chlorine, -O-methyl, and -CF, preferably chlorine and -CF; L is a linker, Selected from the bridging groups -C-C- - OCON-X- X. alkylene, -C-C-alkylene-O-, -C-C-alkylene O-CO-, -C-C-alkylene-NH-, -C-C-alky US 2006/0025420 A1 Feb. 2, 2006 16

lene-NH-CO-, and -C-C-alkenylene, which may optionally be substituted by one or more, preferably -continued one group Selected from among methyl, ethyl, propyl, -OH, chlorine, fluorine, =0 and -CF; R is -NH, -NHC-C-alkyl, -N(C-C-alkyl), or a N N N group Selected from among -C-C-alkyl and -C- O C-cycloalkyl which may optionally be substituted by X 1 X one or more, preferably one group Selected from among -OH, fluorine, chlorine, =O, -CF, -O-phenyl, N N N -O-naphthyl, -NH, -NHmethyl, -N(methyl), -C-C-alkenyl and -C-C-alkynyl, or 1 s 1 ex s R is a phenyl or naphthyl group, optionally Substituted by R4 one or more, preferably one group Selected from among, methyl, ethyl, -OH, fluorine, chlorine, -CF, -O-methyl, -O-ethyl, -NH2, N S N N -NH-methyl, -N(methyl), and a nitrogen contain- 1 2x1 ex ing heteroaromatic ring Selected from among pyri- R", R", dine, pyrimidine, indol, pyrrole, imidazole, pyrazole, O O C triazole, chinoline and isochinoline, wherein Said nitrogen containing heteroaromatic ring may option- N N NH N NN ally be substituted by one or more, preferably one group Selected from among methyl, ethyl, -OH, fluorine, chlorine, -CF, -O-methyl and -O- R", ethyl, and wherein Said nitrogen containing het eroaromatic ring my optionally be linked to the phenyl or naphthyl group via a bridging group B is absent or a ring System Selected from among selected from among -O- and -NH-, or R is a group selected from among N O N O YOX SO.X Y. O. 1 X. 1 X.

5 O. Y O. O. O R", Q R", 1O s N NY SO u1 N

wherein the arrows indicate the positions where the wherein ring is annellated to the five membered nitrogen het 3. erocycle, and wherein X is either N or -CR-, R is selected from among hydrogen, methyl, ethyl, pro Y is either -NR-, -O-, or -CO-; pyl, -CH-N(methyl), and -NGmethyl); A is absent or a ring System Selected from among R" is selected from among hydrogen, methyl, ethyl, pro pyl, -OH, chlorine, fluorine and -CF, R is selected from among hydrogen, methyl, ethyl, pro N N pyl, phenyl, -CH-CH2-phenyl and BenZyl; a pharmaceutically acceptable acid addition Salt thereof, a 1 X 1 X hydrate and/or solvate thereof, or in the form of the R", R", individual optical isomer, a mixture of the individual enantiomers or a racemate thereof. US 2006/0025420 A1 Feb. 2, 2006

9) The method for the treatment of female sexual disor derS according to claim 1, comprising administration of a -continued therapeutically effective amount of a compound of formula 1, wherein R" is a group selected from among fluorine, chlorine, -O-methyl, and -CF, preferably chlorine and -CF; L is a linker, Selected from the bridging groups -C-C- alkylene, -C-C-alkylene-O-, -C-C-alkylene O-CO-, -C-C-alkylene-NH-, -C-C-alky lene-NH-CO-, and -C-C-alkenylene, which may optionally be substituted by one or more, preferably one group Selected from among methyl, ethyl, propyl, -OH, chlorine, fluorine, =0 and -CF; es Ris-NH, -NHC, -C-alkyl, -N(C-C-alkyl), or a group Selected from among -C-C-alkyl and -C- wherein the arrows indicate the positions where the C-cycloalkyl which may optionally be substituted by ring is annellated to the five membered nitrogen one or more, preferably one group Selected from among heterocycle, and wherein -OH, fluorine, chlorine, =O, -CF, -O-phenyl, -O-naphthyl, -NH, -NHmethyl, -N(methyl), R" is selected from among hydrogen, methyl, ethyl, -C-C-alkenyl and -C-C-alkynyl, or propyl, -OH, chlorine, fluorine and -CF, R is a phenyl or naphthyl group, optionally Substituted by a pharmaceutically acceptable acid addition Salt one or more, preferably one group Selected from thereof, a hydrate and/or Solvate thereof, or in the among, methyl, ethyl, -OH, fluorine, chlorine, -CF, form of the individual optical isomer, a mixture of -O-methyl, -O-ethyl, -NH2, the individual enantiomers or a racemate thereof. 10) The method for the treatment of female sexual dis -NH-methyl, -N(methyl), and a nitrogen contain orders according to claim 1, comprising administration of a ing heteroaromatic ring Selected from among pyri therapeutically effective amount of a compound of formula dine, pyrimidine, indol, pyrrole, imidazole, pyrazole, 1, wherein triazole, chinoline and isochinoline, wherein Said nitrogen containing heteroaromatic ring may option R" is a group selected from among chlorine and -CFs, ally be substituted by one or more, preferably one preferably -CF; group Selected from among methyl, ethyl, -OH, L is a linker, selected from -CH-CH-, -CH fluorine, chlorine, -CF, -O-methyl and -O- CH-CH-, -CH-CH-CH-CH-, ethyl, and wherein Said nitrogen containing het O-CH-CH-, O-CH-CH-CH-, eroaromatic ring my optionally be linked to the O-CH-CH-CH-CH-, CO-O phenyl or naphthyl group via a bridging group CH-CH-, CO-O-CH-CH-CH-, selected from among -O- and -NH-, or CO-O-CH-CH-CH-CH-, NH R is a group selected from among. CH-CH-, -N H-CH-CH-CH, -N H-CH-CH-CH-CH-, -CO-N H-CH-CH-, -CO-NH-CH-CH-CH and -CO-NH-CH-CH-CH-CH-, which may optionally be Substituted by one or more, prefer ably one group Selected from among methyl, -OH, Co-Co fluorine, and -CF, R is -NH, -NHC-C-alkyl, -N(C-C-alkyl), or a group Selected from among methyl and ethyl which may optionally be Substituted by one or more, prefer wherein ably one group Selected from among -OH, fluorine, X is either N or -CR ; chlorine, =O,-CF, -O-phenyl, and -NH, or R is selected from among hydrogen, methyl, ethyl, R is a group selected from among cyclopentyl and propyl, -CH-N (methyl), and -NGmethyl), cyclohexyl, which may optionally be Substituted by one or more, preferably one group Selected from among A is a ring System Selected from among -OH, fluorine, -CF, and -C=C-, or R is a phenyl group, optionally Substituted by one or more, preferably one group Selected from among, methyl, -OH, fluorine, -CF, -NH2, and a nitrogen containing heteroaromatic ring Selected from among pyridine, pyrimidine, indol, pyrrole, imidazole, pyra Zole, triazole, chinoline and isochinoline, wherein Said nitrogen containing heteroaromatic ring may optionally US 2006/0025420 A1 Feb. 2, 2006 18

be Substituted by one or more, preferably one group B is absent or a ring System Selected from among Selected from among methyl, -OH, fluorine, and -CF, and wherein Said nitrogen containing heteroaro matic ring my optionally be linked to the phenyl group via a bridging group Selected from among -O- and -NH-, or R is a group selected from among - OCON-X- X.

X X Y. N N N YNN (NY)N s \, A Rí / X. 1 QR DO s^ N4 N2 N ) B \ A : \ B Y, and Y Y 1 NYY. \ B : wherein the arrows indicate the positions where the Y ring is annellated to the five membered nitrogen heterocycle, and wherein wherein R" is selected from among hydrogen, methyl, -OH, fluorine and -CF, X is either N or -CH-, a pharmaceutically acceptable acid addition Salt Y is -O- or -CO-, thereof, a hydrate and/or Solvate or in the form of the individual optical isomer, a mixture of the A is absent or a ring System Selected from among individual enantiomers or a racemate thereof. 11) The method for the treatment of female sexual disor derS according to claim 1, comprising administration of a therapeutically effective amount of a compound of formula 1, wherein OCO R" is a group selected from among chlorine and -CF, - N-X- X. preferably -CF; L is a linker, selected from -CH-CH-, -CH CH-CH-, -CH-CH-CH-CH-, O-CH-CH-, O-CH-CH-CH , O-CH-CH-CH-CH-, CO-O CH-CH-, CO-O-CH-CH-CH-, JDC DO CO-O-CH-CH-CH-CH-, NH CH-CH-, -NH-CH-CH-CH-, -NH CH-CH-CH-CH-, CO-NH-CH CH-, CO-NH-CH-CH-CH and 1CO - N2, CO-NH-CH-CH-CH-CH-, which may optionally be substituted by one or more, preferably one group Selected from among methyl, -OH, fluo rine, and -CF, R’ is -NH, -NHC-C-alkyl, -N(C-C-alkyl), or a group Selected from among methyl and ethyl which may optionally be Substituted by one or more, prefer 1 OOOOex 2. ably one group Selected from among -OH, fluorine, chlorine, =O, -CF, -O-phenyl, and -NH, or R is a group selected from among cyclopentyl and cyclohexyl, which may optionally be Substituted by one or more, preferably one group Selected from among -OH, fluorine, -CF, and -C=C-, or 1 X. 1 s’ and e R is a phenyl group, optionally Substituted by one or more, preferably one group Selected from among, methyl, -OH, fluorine, -CF, -NH2, and a nitrogen US 2006/0025420 A1 Feb. 2, 2006 19

containing heteroaromatic ring Selected from among pyridine, pyrimidine, indol, pyrrole, imidazole, pyra -continued Zole, triazole, chinoline and isochinoline, wherein Said O C nitrogen containing heteroaromatic ring may optionally be Substituted by one or more, preferably one group S. NH and S. Selected from among methyl, -OH, fluorine, and -CF, and wherein Said nitrogen containing heteroaro C matic ring my optionally be linked to the phenyl group 2N\, 2 X.R"; via a bridging group Selected from among -O- and -NH-, or R is a group selected from among wherein the arrows indicate the positions where the ring is annellated to the five membered nitrogen heterocycle, and wherein R" is selected from among hydrogen, methyl, -OH, fluorine and -CF, a pharmaceutically acceptable acid addition Salt Co-Co thereof, a the hydrate and/or Solvate thereof, or in the form of the individual optical isomer, a mix ture of the individual enantiomers or a racemate wherein thereof. X is either N or -CH-, 12) A pharmaceutical composition for the treatment of female Sexual disorders comprising a compound of formula R is selected from among hydrogen, isopropyl and 1 according to claim 1. -CH-N(methyl); 13) A pharmaceutical composition comprising a therapeu tically effective amount of a compound of formula 1 accord A is a ring System Selected from among ing to claim 1 in combination with a therapeutically effective amount of one or more, preferably one active ingredient, preferably an active ingredient Selected from the group consisting of melanocortin agonists, prostaglandin E1 ago nists, elevators of cyclic guanosine 3',5'-monophosphate S N. S. (cGMP) (preferably PDE V inhibitors), 5-HT1A agonists, dopamine agonists, dopamine D4 antagonist and 5-HT2A/C 2. 2 X. antagonists.