Title of article
α-Methylation at benzylic fragment of N-aryl-N′-benzyl ureas provides TRPV1 antagonists with better pharmacokinetic properties and higher efficacy in inflammatory pain model
Author/Authors
Arthur Gomtsyan، نويسنده , , Erol K. Bayburt، نويسنده , , Ryan Keddy، نويسنده , , Sean C. Turner، نويسنده , , Tammie K. Jinkerson، نويسنده , , Stanley Didomenico، نويسنده , , Richard J. Perner، نويسنده , , John R. Koenig، نويسنده , , Irene Drizin، نويسنده , , Heath A. McDonald، نويسنده , , Carol S. Surowy، نويسنده , , Prisca Honore، نويسنده , , Joe Mikusa، نويسنده , , Kennan C. Marsh، نويسنده , , Jill M. Wetter، نويسنده , , Connie R. Faltynek، نويسنده , , Chih-Hung Lee، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2007
Pages
6
From page
3894
To page
3899
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.
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2007
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
798334
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