| Literature DB >> 17583335 |
Richard J Perner1, Stanley DiDomenico, John R Koenig, Arthur Gomtsyan, Erol K Bayburt, Robert G Schmidt, Irene Drizin, Guo Zhu Zheng, Sean C Turner, Tammie Jinkerson, Brian S Brown, Ryan G Keddy, Kurill Lukin, Heath A McDonald, Prisca Honore, Joe Mikusa, Kennan C Marsh, Jill M Wetter, Karen St George, Michael F Jarvis, Connie R Faltynek, Chih-Hung Lee.
Abstract
The synthesis and structure-activity relationship of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of cyclic amine substituents are well tolerated at the 4-position of the benzyl group on compounds containing either an isoquinoline or indazole heterocyclic core. These compounds are potent antagonists of capsaicin activation of the TRPV1 receptor in vitro. Analogues, such as compound 45, have been identified that have good in vivo activity in animal models of pain. Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity.Entities:
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Year: 2007 PMID： 17583335 DOI： 10.1021/jm070276i
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446