Diarylimidazolyl oxadiazole and thiadiazole derivatives as cannabinoid CB1 receptor antagonists.
Since the CB1 receptor antagonist SR141716 (rimonabant) was reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target in the treatment of obesity. Several series of derivatives based on diarylimidazolyl oxadiazole and thiadiazole scaffolds were synthesized and tested for CB1 receptor binding affinity. SAR studies directed toward the optimization of imidazole scaffolds resulted in the discovery of 10s which showed highest potency for CB1 receptor binding affinity (IC(50)=1.91nM) prepared to date.
Kim
Jong Yup
JY
Central Research Laboratories, Green Cross Corporation, Yongin, Gyeonggi-Do, Republic of Korea.
Seo
Hee Jeong
HJ
Lee
Sung-Han
SH
Jung
Myung Eun
ME
Ahn
Kwangwoo
K
Kim
Jeongmin
J
Lee
Jinhwa
J
D000818:Animals; D007093:Imidazoles; D020128:Inhibitory Concentration 50; D009765:Obesity / Q000188:drug therapy; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D007093:Imidazoles; D010069:Oxadiazoles; D043884:Receptor, Cannabinoid, CB1; D013830:Thiadiazoles