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.

Bioorganic & medicinal chemistry 2010 Jul 28; In press

Lee J, Seo H HJ, Lee S SH, Kim J, Jung M ME, Lee S SH, Song K KS, Lee J, Kang S SY, Kim M MJ, Kim M MS, Son E EJ, Lee M, Han H HK

Research Center, Green Cross Corporation, 303 Bojeong-dong, Giheung-gu, Yongin 446-770, Republic of Korea.

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.

Keywords: cannabinoid obesity