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.
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.
Lee
Jinhwa
J
Research Center, Green Cross Corporation, 303 Bojeong-dong, Giheung-gu, Yongin 446-770, Republic of Korea. jinhwa_2_lee@hotmail.com
Seo
Hee Jeong
HJ
Lee
Suk Ho
SH
Kim
Jeongmin
J
Jung
Myung Eun
ME
Lee
Sung-Han
SH
Song
Kwang-Seop
KS
Lee
Junwon
J
Kang
Suk Youn
SY
Kim
Min Ju
MJ
Kim
Mi-Soon
MS
Son
Eun-Jung
EJ
Lee
Minwoo
M
Han
Ho-Kyun
HK
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*
D043884:Receptor, Cannabinoid, CB1; D013830:Thiadiazoles