Diarylimidazolyl oxadiazole and thiadiazole derivatives as cannabinoid CB1 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 1, 2009, Pages 142-145

  Kim, Jong Yup ^a   Seo, Hee Jeong ^a   Lee, Sung Han ^a   Jung, Myung Eun ^a   Ahn, Kwangwoo ^a   Kim, Jeongmin ^a   Lee, Jinhwa ^a  

^a Green Cross Company   (South Korea)

Author keywords

Anti obesity; Cannabinoid receptor antagonist; Imidazole; Rimonabant

Indexed keywords

2 [1 (4 BROMOPHENYL) 2 (2,4 DICHLOROPHENYL) 5 ETHYL 1H IMIDAZOL 4 YL] 5 TERT BUTYL 1,3,4 THIADIAZOLE; CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR ANTAGONIST; RIMONABANT; THIADIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; FOOD INTAKE; HUMAN; MALE; NONHUMAN; OBESITY; RAT; SPRAGUE DAWLEY RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; IMIDAZOLES; INHIBITORY CONCENTRATION 50; OBESITY; OXADIAZOLES; RATS; RECEPTOR, CANNABINOID, CB1; STRUCTURE-ACTIVITY RELATIONSHIP; THIADIAZOLES;

EID: 57749098571     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.10.130     Document Type: Article

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31. 50 was determined from three independent experiments.
32. Several compounds in this series were highly efficacious in in vivo efficacy on the DIO mouse model. One of the compounds in the series showed 25 ± 1% reduction in body weight after 14 days at 10 mg/kg via po. That is a notable piece of information that this series of compounds are indeed CB1R antagonists or inverse agonists, unpublished results.
33. 50 = 5.0 ± 1.0 nM) in each different assay (>1500 compounds tested). Therefore, we believe that all SAR discussions in the manuscript are scientifically meaningful.
34. The compound 10s shows cLog P = 8.0, indicating the highly lipophilic character of 10s just as many other known CB1R ligands are so.