Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1373466 | Bioorganic & Medicinal Chemistry Letters | 2007 | 6 Pages |
Abstract
SAR studies for N-aryl-N′-benzyl urea class of TRPV1 antagonists have been extended to cover α-benzyl alkylation. Alkylated compounds showed weaker in vitro potencies in blocking capsaicin activation of TRPV1 receptor, but possessed improved pharmacokinetic properties. Further structural manipulations that included replacement of isoquinoline core with indazole and isolation of single enantiomer led to TRPV1 antagonists like (R)-16a with superior pharmacokinetic properties and greater potency in animal model of inflammatory pain.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Arthur Gomtsyan, Erol K. Bayburt, Ryan Keddy, Sean C. Turner, Tammie K. Jinkerson, Stanley Didomenico, Richard J. Perner, John R. Koenig, Irene Drizin, Heath A. McDonald, Carol S. Surowy, Prisca Honore, Joe Mikusa, Kennan C. Marsh, Jill M. Wetter,