Design, synthesis and biological evaluation of B-region modified diarylalkyl amide analogues as novel TRPV1 antagonists.
Design, synthesis and biological evaluation of B-region, known to be a dipolar interacting pharmacophore, modified diarylalkyl amide analogues for novel TRPV1 (transient receptor potential channel, vanilloid subfamily member 1) antagonists was described. A variety of moieties including guanidines, heterocyclic rings, cinnamides, and α-substituted acetamides were introduced at the B-region. TRPV1 antagonistic activities of these analogues were evaluated by (45)Ca(2+) uptake assay in rat DRG neuron. In particular, α,α-difluoroamide 53 exhibited 3-fold more potent TRPV1 antagonistic activity (IC50 = 0.058 μM) than the parent amide analogue 6.
College of Pharmacy, Woosuk University, Wanju, 565-701, Republic of Korea.
Young Taek
YT
Han
Shao-Mei
SM
Yang
Xiao-Yuan
XY
Wang
Fu-Nan
FN
Li
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015195:Drug Design; D005727:Ganglia, Spinal / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
D000577:Amides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002118:Calcium