title: Bioisosteric replacement of the pyrazole 3-carboxamide moiety of rimonabant. A novel series of oxadiazoles as CB1 cannabinoid receptor antagonists.
abstract: 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.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 350, Taiwan, ROC.
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Chu
authors.forename: Ming-Shiu
authors.initials: MS
authors.lastname: Hung
authors.forename: Min-Tsang
authors.initials: MT
authors.lastname: Hsieh
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Kuo
authors.forename: T D
authors.initials: TD
authors.lastname: Suja
authors.forename: Jen-Shin
authors.initials: JS
authors.lastname: Song
authors.forename: Hua-Hao
authors.initials: HH
authors.lastname: Chiu
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Kak-Shan
authors.initials: KS
authors.lastname: Shia
mesh_terms: 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
chemical_list: D000577:Amides; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C031280:pyrazole; D000077285:Rimonabant