Design, synthesis, and biological evaluation of novel alkenylthiophenes as potent and selective CB1 cannabinoid receptor antagonists.
A novel class of (5-(pent-1-enyl)thiophen-2-yl)pyrazole antagonists was discovered, many of which exhibited potent CB1 activity and good CB1/2 selectivity, suggesting that along with a 1,3-transposition of the carbonyl of the pyrazole 3-carboxamide, bioisosteric replacement of the conventional pyrazole 5-aryl group with a thienyl ring substituted with an appropriate alkenyl moiety is viable.
Tai
Chia-Liang
CL
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 350, Taiwan, Republic of China.
Hung
Ming-Shiu
MS
Pawar
Vijay D
VD
Tseng
Shi-Liang
SL
Song
Jen-Shin
JS
Hsieh
Wan-Ping
WP
Chiu
Hua-Hao
HH
Wu
Hui-Chuan
HC
Hsieh
Min-Tsang
MT
Kuo
Chun-Wei
CW
Hsieh
Chia-Chien
CC
Tsao
Jing-Po
JP
Chao
Yu-Sheng
YS
Shia
Kak-Shan
KS
D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013379:Substrate Specificity; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013876:Thiophenes