2. Academic Validation
  3. Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists

Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists

  • Bioorg Med Chem Lett. 2008 Sep 15;18(18):5118-22. doi: 10.1016/j.bmcl.2008.07.112.
Markian M Stec 1,  Yunxin Bo,  Partha P Chakrabarti,  Lillian Liao,  Mqhele Ncube,  Nuria Tamayo,  Rami Tamir,  Narender R Gavva,  James J S Treanor,  Mark H Norman
Affiliations

Affiliation

  • 1 Department of Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. mstec@amgen.com
PMID: 18722118 DOI: 10.1016/j.bmcl.2008.07.112
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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