title: Discovery of 2-(4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-bromophenyl)-1-(2-chlorophenyl)-1H-pyrazol-3-yl)-5-tert-butyl-1,3,4-thiadiazole (GCC2680) as a potent, selective and orally efficacious cannabinoid-1 receptor antagonist.
abstract: Structure-activity relationship studies in a series of diarylpyrazolyl thiadiazoles identified cannabinoid-1 receptor antagonists with excellent potency and selectivity. Based on its exceptional in vivo efficacy in animal models and its favorable pharmacokinetic and toxicological profiles, 2-(4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-bromophenyl)-1-(2-chlorophenyl)-1H-pyrazol-3-yl)-5-tert-butyl-1,3,4-thiadiazole (GCC2680) was selected as a preclinical candidate for the treatment of obesity.
authors.affiliation: Research Center, Green Cross Corporation, 303 Bojeong-dong, Giheung-gu, Yongin 446-770, Republic of Korea. jinhwa_2_lee@hotmail.com
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Seo
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Kim
authors.forename: Myung Eun
authors.initials: ME
authors.lastname: Jung
authors.forename: Sung-Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Kwang-Seop
authors.initials: KS
authors.lastname: Song
authors.forename: Junwon
authors.initials: J
authors.lastname: Lee
authors.forename: Suk Youn
authors.initials: SY
authors.lastname: Kang
authors.forename: Min Ju
authors.initials: MJ
authors.lastname: Kim
authors.forename: Mi-Soon
authors.initials: MS
authors.lastname: Kim
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Son
authors.forename: Minwoo
authors.initials: M
authors.lastname: Lee
authors.forename: Ho-Kyun
authors.initials: HK
authors.lastname: Han
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D043884:Receptor, Cannabinoid, CB1; D013830:Thiadiazoles