Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: Constraint-induced enhancement of in vitro and in vivo activities

Nam Jung Kim, Fu Nan Li, Jin Hee Lee, Seul Gi Park, Kyeojin Kim, Changjin Lim, Young Taek Han, Hwayoung Yun, Jong Wha Jung, Hyeung Geun Park, Hee Doo Kim, Byoung Young Woo, Song Seok Shin, Sun Young Kim, Jin Kyu Choi, Yeon Su Jeong, Yanghui Park, Young Ho Park, Dae Duk Kim, Sun ChoiYoung Ger Suh

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model. Flexibility not desired: A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model.

Original languageEnglish
Pages (from-to)400-409
Number of pages10
JournalChemistry - An Asian Journal
Volume8
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • TRVP1
  • antagonists
  • ligand design
  • medicinal chemistry
  • molecular modeling

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