Bioisosteric replacement of the pyrazole 3-carboxamide moiety of rimonabant. A novel series of oxadiazoles as CB1 cannabinoid receptor antagonists.
Based on the bioisosteric replacement of the pyrazole C3-carboxamide of rimonabant with a 5-alkyl oxadiazole ring, a novel class of oxadiazole derivatives with promising biological activity towards CB1 receptors was discovered. Among them, compounds with an alkyl linker containing a strong electron-withdrawing group (e.g., CF(3)) and a sterically favorable bulky group (e.g., t-butyl) exhibited excellent CB1 antagonism and selectivity, and thus might serve as potential candidates for further development as anti-obesity agents.
Chu
Cheng-Ming
CM
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 350, Taiwan, ROC.
Hung
Ming-Shiu
MS
Hsieh
Min-Tsang
MT
Kuo
Chun-Wei
CW
Suja
T D
TD
Song
Jen-Shin
JS
Chiu
Hua-Hao
HH
Chao
Yu-Sheng
YS
Shia
Kak-Shan
KS
D000577:Amides / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007536:Isomerism; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism*; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077285:Rimonabant; D013329:Structure-Activity Relationship
D000577:Amides; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C031280:pyrazole; D000077285:Rimonabant