2-(4-Methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the B and C-regions

Bioorg Med Chem. 2012 Feb 1;20(3):1310-8. doi: 10.1016/j.bmc.2011.12.014. Epub 2011 Dec 23.

Abstract

On the basis of the previous lead N-4-t-butylbenzyl 2-(3-fluoro-4-methylsulfonylaminophenyl) propanamide (3) as a potent TRPV1 antagonist, structure-activity relationships for the B (propanamide part) and C-region (4-t-butylbenzyl part) have been investigated for rTRPV1 in CHO cells. The B-region was modified with dimethyl, cyclopropyl and reverse amides and then the C-region was replaced with 4-substituted phenyl, aryl alkyl and diaryl alkyl derivatives. Among them, compound 50 showed high binding affinity with K(i)=21.5nM, which was twofold more potent than 3 and compound 54 exhibited potent antagonism with K(i(ant))=8.0nM comparable to 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemistry*
  • Analgesics / pharmacology*
  • Animals
  • CHO Cells
  • Cricetinae
  • Humans
  • Mesylates / chemistry*
  • Mesylates / pharmacology*
  • Phenylpropionates / chemistry*
  • Phenylpropionates / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / metabolism

Substances

  • 2-(4-methylsulfonylaminophenyl)propanamide
  • Analgesics
  • Mesylates
  • Phenylpropionates
  • TRPV Cation Channels