Synthesis and structural optimization of multiple H-bonding region of diarylalkyl (thio)amides as novel TRPV1 antagonists

Bioorg Med Chem. 2009 Dec 15;17(24):8149-60. doi: 10.1016/j.bmc.2009.10.043. Epub 2009 Oct 27.

Abstract

Structural optimization of multiple H-bonding region and structure-activity relationship of diarylalkyl amides/thioamides as novel TRPV1 antagonists are described. In particular, we identified amide 34o and thioamides 35o and 35r, of which antagonistic activities were highly enhanced by an incorporation of cyano or vinyl-substituent to the multiple H-bonding region. They exhibited potent (45)Ca(2+) uptake inhibitions in rat DRG neuron with IC(50)s of 25, 32 and 28 nM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / metabolism
  • Amides / pharmacology*
  • Animals
  • Binding Sites
  • Calcium / metabolism
  • Calcium Signaling / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Inhibitory Concentration 50
  • Neurons / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • TRPV Cation Channels / antagonists & inhibitors*

Substances

  • Amides
  • TRPV Cation Channels
  • Calcium