Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists |
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| Authors: | 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 |
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| Affiliation: | Department of Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. mstec@amgen.com |
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| 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. |
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