Design, synthesis, and biological evaluation of phenylpropanamides as novel transient receptor potential vanilloid 1 antagonists.
Synthesis and structure-activity relationship of N-benzyl-3-phenylpropanamides as transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of substituents such as halide, ester, nitro, and alkyl groups at 2 or 3-position of 4-(methylsulfonylamino) benzyl unit were examined. These compounds exhibited potent 45Ca2+ uptake inhibition in rat DRG neuron via TRPV1 blockade. Especially compound 28c, has been identified as a potent antagonist with IC50 of 38 nM.
Li
Fu-Nan
FN
College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Kim
Nam-Jung
NJ
Nam
Yeon-Hee
YH
Kim
Seung-Hee
SH
Seo
Seung-Yong
SY
Jeong
Yeon-Su
YS
Kim
Sun-Young
SY
Park
Young-Ho
YH
Suh
Young-Ger
YG
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 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
D000577:Amides; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D002118:Calcium