Tetrazole-biarylpyrazole derivatives as cannabinoid CB1 receptor antagonists.
Cannabinoid CB1 receptors have been the focus of extensive studies since the first clinical results of rimonabant (SR141716) for the treatment of obesity and related metabolic disorders were reported in 2001. To further evaluate the properties of CB receptors, we have designed a new series of tetrazole-biarylpyrazoles. The various analogues were efficiently prepared and bio-assayed for binding to cannabinoid CB1 receptor. Six of the new compounds which displayed high in vitro CB1 binding affinities were assayed for binding to CB2 receptor. Noticeably, cyclopentyl-tetrazole (9a) demonstrated good binding affinity and selectivity for CB1 receptor (IC(50)=11.6nM and CB2/CB1=366).
Kang
Suk Youn
SY
Small Molecule Group, Central Research Institute, Green Cross Corporation, 341 Bojeong-Dong, Giheung-Gu, Yongin, Gyunggi-Do 446-799, Republic of Korea.
Lee
Sung-Han
SH
Seo
Hee Jeong
HJ
Jung
Myung Eun
ME
Ahn
Kwangwoo
K
Kim
Jeongmin
J
Lee
Jinhwa
J
D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008024:Ligands; D008956:Models, Chemical; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000494:pharmacology*
D019440:Anti-Obesity Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013777:Tetrazoles