Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists

Bioorganic & Medicinal Chemistry Letters
Markian StecMark H Norman

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.

References

Feb 29, 2000·British Journal of Pharmacology·D SmartJ B Davis
Jun 26, 2007·Journal of Medicinal Chemistry·Mark H NormanJames J S Treanor
Oct 17, 2007·Bioorganic & Medicinal Chemistry Letters·Xianghong WangMark H Norman

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