Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists

…, PP Chakrabarti, L Liao, M Ncube, N Tamayo…

Index: Stec, Markian M.; Bo, Yunxin; Chakrabarti, Partha P.; Liao, Lillian; Ncube, Mqhele; Tamayo, Nuria; Tamir, Rami; Gavva, Narender R.; Treanor, James J.S.; Norman, Mark H. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 18 p. 5118 - 5122

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Citation Number: 11

Abstract

Clinical candidate AMG 517 (1) is a potent antagonist toward multiple modes of activation of TRPV1; however, it suffers from poor solubility. Analogs with various substituents at the R region of 3 were prepared to improve the solubility while maintaining the potent TRPV1 activity of 1. Compounds were identified that maintained potency, had good pharmacokinetic properties, and improved solubility relative to 1.