Novel potent antagonists of transient receptor potential channel, vanilloid subfamily member 1: structure-activity relationship of 1,3-diarylalkyl thioureas possessing new vanilloid equivalents

  • J Med Chem. 2005 Sep 8;48(18):5823-36. doi: 10.1021/jm0502790.
Young-Ger Suh  1 ,  Yong-Sil Lee ,  Kyung-Hoon Min ,  Ok-Hui Park ,  Jin-Kwan Kim ,  Ho-Sun Seung ,  Seung-Yong Seo ,  Bo-Young Lee ,  Yeon-Hee Nam ,  Kwang-Ok Lee ,  Hee-Doo Kim ,  Hyeung-Geun Park ,  Jeewoo Lee ,  Uhtaek Oh ,  Ju-Ok Lim ,  Sang-Uk Kang ,  Min-Jung Kil ,  Jae-Yeon Koo ,  Song Seok Shin ,  Yung-Hyup Joo ,  Jin Kwan Kim ,  Yeon-Su Jeong ,  Sun-Young Kim ,  Young-Ho Park
Affiliations
  • 1. College of Pharmacy, and Sensory Research Center, CRI, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Korea. [email protected]
PMID: 16134949 DOI: 10.1021/jm0502790
Abstract

Recently, 1,3-diarylalkyl thioureas have merged as one of the promising nonvanilloid TRPV1 antagonists possessing excellent therapeutic potential in pain regulation. In this paper, the full structure-activity relationship for TRPV1 antagonism of a novel series of 1,3-diarylalky thioureas is reported. Exploration of the structure-activity relationship, by systemically modulating three essential pharmacophoric regions, led to six examples of 1,3-dibenzyl thioureas, which exhibit CA(2+) uptake inhibition in rat DRG neuron with IC(50) between 10 and 100 nM.