Patent
Substituted N-sulfonylaminophenylethyl-2-phenoxyacetamide compounds as VR1 receptor antagonists
| العنوان: | Substituted N-sulfonylaminophenylethyl-2-phenoxyacetamide compounds as VR1 receptor antagonists |
|---|---|
| Patent Number: | 7,566,739 |
| تاريخ النشر: | July 28, 2009 |
| Appl. No: | 11/372706 |
| Application Filed: | March 10, 2006 |
| مستخلص: | This invention provides compounds of the formula (I) useful for the treatment of disease conditions caused by over activation of Vr1 receptors such as pain or the like in mammals as well as compositions comprising them. |
| Inventors: | Hanazawa, Takeshi (Aichi-ken, JP); Hirano, Misato (Aichi-ken, JP); Inoue, Tadashi (Aichi-ken, JP); Nagayama, Satoshi (Aichi-ken, JP); Nakao, Kazunari (Aichi-ken, JP); Shishido, Yuji (Aichi-ken, JP); Tanaka, Hirotaka (Aichi-ken, JP) |
| Assignees: | Pfizer Inc. (New York, NY, US) |
| Claim: | 1. A compound of the formula (I): [chemical expression included] wherein R 1 represents (C 1 -C 6)alkyl; R 2 represents hydrogen, halogen, hydroxy, (C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, hydroxy(C 1 -C 6) alkyl, (C 1 -C 6)alkoxy-(C 1 -C 6)alkyl or halo(C 1 -C 6)alkyl; R 3 represents a halogen atom, (C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, hydroxy(C 1 -C 6)alkoxy, (C 1 -C 6) alkoxy-(C 1 -C 6)alkyl, (C 1 -C 6)alkoxy-(C 1 -C 6)alkoxy, halo(C 1 -C 6)alkyl, (C 1 -C 6) alkylthio, (C 1 -C 6) alkylsulfinyl, (C 1 -C 6)alkylsulfonyl, [(C 1 -C 6)alkyl]NH—, or[(C 1 -C 6)alkyl] 2 N—; R 4 represents a halogen atom, (C 1 -C 6)alkyl, halo(C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, hydroxy(C 1 -C 6) alkoxy, (C 1 -C 6)alkoxy-(C 1 -C 6)alkyl, (C 1 -C 6)alkoxy-(C 1 -C 6)alkoxy, [(C 1 -C 6) alkyl]NH—, or[(C 1 -C 6)alkyl] 2 N—; R 5 represents a halogen atom, (C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, hydroxy(C 1 -C 6)alkoxy, (C 1 -C 6) alkoxy-(C 1 -C 6)alkyl, (C 1 -C 6)alkoxy-(C 1 -C 6)alkoxy, halo(C 1 -C 6)alkyl, (C 1 -C 6)alkylthio, (C 1 -C 6)alkylsulfinyl, (C 1 -C 6)alkylsulfonyl, [(C 1 -C 6)alkyl]NH—, [(C 1 -C 6)alkyl] 2 N—, H 2 N—(C 1 -C 6)alkoxy, (C 1 -C 6)alkyl-NH—(C 1 -C 6)alkoxy, [(C 1 -C 6)alkyl] 2 N—(C 1 -C 6)alkoxy, H 2 N—(C 1 -C 6)alkoxy-(C 1 -C 6)alkyl, (C 1 -C 6)alkyl-NH—(C 1 -C 6)alkoxy-(C 1 -C 6)alkyl, or [(C 1 -C 6)alkyl] 2 N(C 1 -C 6)alkoxy-(C 1 -C 6)alkyl; and * indicates a chiral centre; or a pharmaceutically acceptable salt or solvate thereof. |
| Claim: | 2. A compound according to claim 1 , wherein R 1 represents methyl. |
| Claim: | 3. A compound according to claim 1 , wherein R 2 represents hydrogen, hydroxy, hydroxymethyl, fluoro, chloro or methoxy. |
| Claim: | 4. A compound according to claim 1 , wherein R 3 represents halogen or (C 1 -C 3)alkoxy. |
| Claim: | 5. A compound according to claim 1 , wherein R 3 represents fluoro. |
| Claim: | 6. A compound according to claim 1 , wherein R 4 represents (C 1 -C 6)alkyl, or halo(C1-C 6)alkyl. |
| Claim: | 7. A compound according to claim 1 , wherein R 4 represents tert-butyl or 2,2,2-trifluoro-1,1-dimethylethyl. |
| Claim: | 8. A compound according to claim 1 , wherein R 5 represents halogen or (C 1 -C 3)alkoxy. |
| Claim: | 9. A compound according to claim 1 , wherein R 5 represents fluoro. |
| Claim: | 10. A compound according to claim 1 to selected from the group consisting of: 2-(4-tert-butyl-3,5-difluorophenoxy)-N-(1-{3-methyl-4-[(methylsulfonyl) amino]phenyl}ethyl)acetamide; 2-(4-tert-butyl-3,5-difluorophenoxy)-N-(1-{3-fluoro-4-[(methylsulfonyl) amino]phenyl}ethyl)acetamide; 2-(4-tert-butyl-3,5-difluorophenoxy)-N-(1-{4-[(methylsulfonyl) amino]phenyl}ethyl)acetamide; 2-(4-tert-butyl-3,5-difluorophenoxy)-N-(1-{3-hydroxymethyl-4-[(methylsulfonyl) amino]phenyl}ethyl)acetamide; and 2-(4-{2,2,2-trifluoro-1;1-dimethylethyl)-3,5-difluorophenoxy)-N-(1-{3-methyl-4-[(methylsulfonyl) amino]phenyl}ethyl)acetamide; or a pharmaceutically acceptable salt or solvate thereof. |
| Claim: | 11. A compound according to claim 1 , wherein the compounds of formula (I) have (R) stereochemistry at the position marked *. |
| Claim: | 12. A pharmaceutical composition comprising a compound of the formula (I), or a pharmaceutically acceptable salt or solvate thereof, as defined in claim 1 , together with a pharmaceutically acceptable excipient. |
| Current U.S. Class: | 514/605 |
| Patent References Cited: | 7214824 May 2007 Inoue et al. 2002/0091116 July 2002 Zhu et al. 2004/0116399 June 2004 Zhu et al. 2005/0085449 April 2005 Dalton et al. 0241043 October 1987 WO9631475 October 1996 WO0119788 March 2001 WO0119798 March 2001 WO0164642 September 2001 WO0216318 February 2002 WO0216319 February 2002 WO03031394 April 2003 WO03097047 November 2003 WO2004035533 April 2004 WO 2005/003084 January 2005 WO2005040093 May 2005 |
| Other References: | C. Deal, et al., “Treatment of Arthritis with Topical Capsaicin:Double-Blind Trial”, Clin Ther, 1991, pp. 383-395, vol. 13, No. 3. cited by other J. Fernihough, et al., “Regulation of Calcitonin Gene-related Peptide and TRPV1 in a Rat Model of Osteoarthritis”, Neuroscience Letters, Nov. 2005, pp. 75-80, vol. 388, No. 2. cited by other P. Honore, et al., “A-425619 [1-Isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a Novel Transient Receptor Potential Type V1 Receptor Antagonist, Relieves Pathophysiological Pain Associated with Inflammation and Tissue Injury in Rats”, J Pharmacol Exp Ther, 2005, pp. 410-421, vol. 314 No. 1. cited by other R. Planells-Cases, et al., Functional Aspects and Mechanisms of TRPV1 Involvement in Neurogenic Inflammation that Leads to Thermal Hyperalgesia, Eur J Physiol, 2005, pp. 151-159, vol. 451. cited by other |
| Primary Examiner: | O'Sullivan, Peter G |
| Attorney, Agent or Firm: | Benson, Gregg C. Olson, A. Dean |
| رقم الانضمام: | edspgr.07566739 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |