Discovery of N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea as a potent TRPV1 antagonistic template.

A series of homologous analogues of prototype antagonist 1 and its urea surrogate were investigated as h TRPV1 ligands. Through one-carbon elongation in the respective pharmacophoric regions, N -(3-fluoro-4-methylsulfonamidomethylphenyl)urea was identified as a novel and potent TRPV1 antagonistic template. Its representative compound 27 showed a potency comparable to that of lead compound 1 . Docking analysis of compound 27 in our h TRPV1 homology model indicated that its binding mode was similar with that of 1 S . [ABSTRACT FROM AUTHOR]