TRPV1 modulators: Synthesis and in vitro evaluation of 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives

Eur J Med Chem. 2015 Jul 15:100:129-38. doi: 10.1016/j.ejmech.2015.05.041. Epub 2015 Jun 6.

Abstract

A series of new 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives was synthesized and evaluated as TRPV1 modulators in a Ca(2+) channel assay in HEK-293 cells overexpressing the human recombinant TRPV1 channel. Structural variations in the putative key portions of the molecules afforded several compounds endowed with agonist and/or antagonist/desensitizing activity at low micromolar concentration. As promising examples from this series, the piperidine-3-carboxamide derivative 31 exerts agonist/desensitizing activity at low micromolar concentration, while piperazinylurea derivatives 39 and 41 act as antagonists with sub-micromolar potency.

Keywords: Calcium channel assay; Piperazinylureas; Piperidinecarboxamides; TRPV1 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Structure-Activity Relationship
  • TRPV Cation Channels / agonists*
  • TRPV Cation Channels / antagonists & inhibitors*
  • Urea / analogs & derivatives
  • Urea / chemistry
  • Urea / pharmacology*

Substances

  • Amides
  • Piperidines
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Urea