USOO7687533B2 (12) United States Patent (10) Patent No.: US 7,687,533 B2 Critcher et al. (45) Date of Patent: Mar. 30, 2010 (54) N-(1-ARYLPYRAZOL-4L) SULFONAMIDES EP 546391 6, 1993 AND THEIR USE AS PARASITICDES EP 59.4291 4f1994 EP 626.375 11, 1994 (75) Inventors: Douglas James Critcher, Sandwich EP 1319657 6, 2003 (GB); Nigel Derek Arthur Walshe, WO WO87,03781 7, 1987 Sandwich (GB); Christelle Lauret, WO WO91f11172 8, 1991 Sandwich (GB) WO WO93, 19053 9, 1993 WO WO93,25543 12/1993 (73) Assignees: Pfizer Inc., New York, NY (US); Pfizer WO WO94/O2518 2, 1994 Products Inc., Groton, CT (US) WO WO94, 15944 T 1994 - WO WO94,21606 9, 1994 (*) Notice: Subject to any disclaimer, the term of this WO WO95/22552 8, 1995 patent is extended or adjusted under 35 WO WO96, 11945 4f1996 U.S.C. 154(b) by 607 days. WO WO96, 15121 5, 1996 WO WO98,24767 6, 1998 (21) Appl. No.: 10/593,133 WO WO98.28278 7, 1998 WO WO98,55148 12/1998 (22) PCT Filed: Mar. 7, 2005 WO WO98,57937 12/1998 (86). PCT No.: PCT/B2005/000597 W WS 1 3. S 371 (c)(1) WO WOO1, 19798 3, 2001 (2), (4) Date: Nov.30, 2006 WO WOO2/O58690 8, 2002 WO WOO3,O37274 5, 2003 (87) PCT Pub. No.: WO2005/090313 WO WOO3,051833 6, 2003 WO WO2004/OOO318 12/2003 PCT Pub. Date: Sep. 29, 2005 WO WO2004/043951 5, 2004 WO WO2004/043951 A1 * 5, 2004 (65) Prior Publication Data WO WO2004/049797 6, 2004 US 2008/O26 1940 A1 Oct. 23, 2008 Related U.S. Application Data OTHER PUBLICATIONS (60) Provisional application No. 60/.571,415, filed on May Vippagunta et al. (Advanced Drug Delivery Reviews, 48 (2001), pp. 13, 2004. 3-26).* (Continued) (30) Foreign Application Priority Data Primary Examiner Kamal A Saeed Mar. 18, 2004 (GB) ................................. O4O6137.O Assistant Examiner Valerie Rodriguez-Garcia (74) Attorney, Agent, or Firm Thomas A. Wootton; Paul M. (51) Int. Cl. Misiak AOIN 43/56 (2006.01) (52) U.S. Cl. .................................... 514/.407: 548/371.4 (57) ABSTRACT (58) Field of Classification Search ................. 514/.407; 548/371.4 See application file for complete search history. The invention relates to a sulfonamide compound of formula (I) or a pharmaceutically, veterinarily or agriculturally (56) References Cited acceptable salt or solvate thereof, where the groups R'-Rare described in the description, to compositions comprising U.S. PATENT DOCUMENTS Such compounds, processes for their synthesis and their use as 5,015,630 A 5, 1991 Fisher et al. parasiticides. 5,478,855 A 12/1995 Suzuki et al. 5,618,945 A 4/1997 Cazado et al. 6,106,864 A 8, 2000 Dolan et al. (I) 2002fOO16333 A1 2/2002 Faraci et al. * Rs FOREIGN PATENT DOCUMENTS R2 N-k DE 19511269 10, 1995 ( \ \, DE 1952O936 12/1996 N EP 192951 1, 1986 YN R5 EP 234119 12, 1986 EP 3O2328 2, 1989 k EP 357460 3, 1990 EP 382173 8, 1990 EP 444964 9, 1991 EP 503.538 9, 1992 8 Claims, No Drawings US 7.687,533 B2 Page 2 OTHER PUBLICATIONS Chemical abstracts service, Columbus, OH, USA Xp002330926, retrieved from STN accession No. 1964:3141 rn 947 11-31-6. Souillac, et al., Characterization of Delivery Systems, Differential Database crossfire beilstein institut Zur foerderung der chemischen Scanning Calorimetry, pp. 217-218 (in Encyclopedia of Controlled wissenschaften; Xp002330927 Beilstein registry No. 316683. Drug Delivery, 1999, John Wiley & Sons, pp. 212-227).* GuarneriMetal. “Contributo allaconoscenzadi pirazolsulfonamidi s Haleblian, Journal of Pharmaceutical Science, 64(8), pp. 1269-1288, Annali di Chimica, vol. 49, 1959, pp. 958-963. Aug. 1985. Koch Aetal. Quantitative Structure-Activity Relationships. vol. 12, Larsen. “Design and Application of prodrugs.” Textbook of Drug No. 4, 1993 pp. 373-382. Design and Discovery, 3rd Edition, 2002, pp. 410-458, Taylor and Alberti Cetal. Farmaco, Edizione Scientifica, vol. 21, No. 12, 1966, Francis Ltd., London. pp. 883-891. Liang and Chen, Expert Opinion in Therapeutic Patents, 11(6), pp. Alberti C et al. Farmaco, Edizione Scientifica, vol. 19, No. 7, 1964, 981-986, 2001. pp. 618-637. Verma et al., Pharmaceutical Technology On-line, 25(2), 1-14, 2001. Alberti C et al. Farmaco, Edizione Scientifica, vol. 17, No. 6, 1962, Finnin and Mogan, Journal Pharm Sci. 88(10). 955-958, Oct. 1999. pp. 460-467. Wolniewicz & Dmowski, J. Fluorine Chem., 2001, 109, 2, 95 (wo Alberti C et al. Farmaco, Edizione Scientifica, vol. 29, No. 12, 1974 spec p. 124). pp. 957-966. Hainzl, D., et al. Chemical Research in Toxicology, 11(12), pp. Alberti C et al. Farmaco, Edizione Scientifica, vol. 26, No. 1, 1971, 1529-1535, 1998. pp. 66-88. Hall, H.K., et al. Journal of the American Chemical Society. 97(4), Fusco, R. et al. Farmaco, Edizione Scientifica, vol. 23, No. 19, 1968 pp. 800-807, 1975. pp. 919-944. Chemical Abstracts Service, Columbus OH, USA; xp002330925, retrieved from STN. Accession No. 1969:36415, m 23142-47-4. * cited by examiner US 7,687,533 B2 1. 2 N-(1-ARYLPYRAZOL-4L) SULFONAMIDES ing parasites and prevent infestation. This has benefits in AND THEIR USE AS PARASITICDES terms of compliance and labour costs as less frequent dosing is needed and the dosing timetable is easier. This in turn CROSS-REFERENCE TO RELATED assists in minimising the re-incidence of infestation as a Sub APPLICATIONS sequent dosage is less likely to be overlooked. It is an aim of the present invention to overcome various This application is the national phase of international disadvantages of or improve on the properties of prior art application PCT/IB2005/000597, filed on Mar. 7, 2005 which compounds. Thus it is an aim of the invention to provide an claims the benefit of Great Britain Application No. arylpyrazole which has improved activity relative to prior art 0406137.0, filed Mar. 18, 2004 and U.S. Provisional Appli 10 cation No. 60/571,415, filed May 13, 2004, hereby incorpo compounds against parasites. The compounds of the present rated by reference in its entirely. invention have especially good ability to control a broad The present invention relates to pesticidal compounds and spectrum of arthropods as shown by the results of tests dem a process for their preparation. More particularly, the present onstrating their potency and efficacy. Surprisingly, we have invention relates to N-(1-arylpyrazol-4-yl)sulfonamides 15 found that the compounds of the present invention are signifi which possess antiparasitic activity. In particular, we have cantly more active against fleas and/or have a greater duration identified a series of N-(1-arylpyrazol-4-yl)sulfonamides of action than similar prior art compounds. One advantage of which have improved activity and/or a longer duration of the compounds of the present invention is that treatment with action and/or improved safety. these compounds can also lead to a reduced incidence of Sulphamoyl (reversed Sulphonamides) arylpyrazoles for allergy to the parasite which is responsible for the infestation. the control of arthropod, plant nematode, or helminth pests For example, the incidence of flea allergies which can cause have also been disclosed in, for example, EP-234119, flea allergic dermatitis may be reduced. US-2002016333, WO-0258690 and DE-19511269. It is also desirable that the compounds of the present inven 5-Sulphonamido-1-arylpyrazoles have been disclosed as tion should have an improved pharmacokinetic profile, having utility as herbicides in, for example, EP-0192951 and 25 improved safety, longer half-life, improved persistence and EP-3O2328. improved solubility. It is also desired that the compounds U.S. Pat. No. 5,618.945 relates to a process for sulphiny should lead to a reduced incidence of emesis. lation of compounds such as arylpyrazoles, by the treatment Unfortunately, many potent pesticidal aryl pyrazoles and of a compound such as RS(O)X, where X is commonly Cl, their derivatives also have undesirable effects such as emesis and discloses compounds of formula R—S(O)NH-Het where 30 Het can be N-arylpyrazole, although it is not clear which on animals regardless of whether or not the animal itself is substitution pattern is referred to. being treated directly. This unwanted toxicity can limit the Some pyrazoles possessing bactericidal activity are dis dose that can be used and thus limits the range of parasites that closed in WO-9315060 for use in crop protection. Among the can be controlled. Thus it is an aim of the present invention to many structures disclosed are some N-heterocyclic pyrazol 35 address the need for the development and use of new and 4-yl Sulfonamides. efficacious pesticides that can control pests for longer periods WO00/71532, WO03/51833, WO01/19788, WO01/ of time but which are not toxic to animals susceptible to pest 19798, WO03/37274, WOO4/00318, WO98/57937 and infestations or animals that might come into contact with WO96/12706 all generally describe pyrazole compounds for areas Susceptible to pest infestations. uses unrelated to those described for the present invention. 40 It is a further aim to provide a convenient, synthetically The prior art compounds do not always demonstrate good efficient process for the production of the aryl pyrazoles and activity or a long duration of action against parasites. Simi the intermediates of the present invention. It is also an aim to larly, some parasiticidal agents are useful only for a narrow provide a route to the compounds of the invention which spectrum of parasites. Modern pesticides must meet many offers a good yield and which ideally avoids the use of unnec demands, including long duration, broad spectrum of action, 45 essary synthetic steps and/or purification steps.