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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2009-7-16
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pubmed:abstractText |
By using the active metabolite 5 as an initial template, further structural modifications led to the identification of the titled compound 24 (BPR-890) as a highly potent CB1 inverse agonist possessing an excellent CB2/1 selectivity and remarkable in vivo efficacy in diet-induced obese mice with a minimum effective dose as low as 0.03 mg/kg (po qd) at the end of the 30-day chronic study. Current SAR studies along with those of many existing rimonabant-mimicking molecules imply that around the pyrazole C3-position, a rigid and deep binding pocket should exist for CB1 receptor. In addition, relative to the conventional carboxamide carbonyl, serving as a key hydrogen-bond acceptor during ligand-CB1 receptor interaction, the corresponding polarizable thione carbonyl might play a more critical role in stabilizing the Asp366-Lys192 salt bridge in the proposed CB1-receptor homology model and inducing significant selectivity for CB1R over CB2R.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:ChangChun-PingCP,
pubmed-author:ChaoYu-ShengYS,
pubmed-author:ChouMing-ChenMC,
pubmed-author:ChuCheng-MingCM,
pubmed-author:ChungWan-LingWL,
pubmed-author:HsiehMin-TsangMT,
pubmed-author:HsiehWan-PingWP,
pubmed-author:HungMing-ShiuMS,
pubmed-author:JanJiing-JyhJJ,
pubmed-author:KuoChun-WeiCW,
pubmed-author:LinChin-YuCY,
pubmed-author:LinYinchiuY,
pubmed-author:ShiaKak-ShanKS,
pubmed-author:ShyHorng-ShingHS,
pubmed-author:SongJen-ShinJS,
pubmed-author:TsengShi-LiangSL,
pubmed-author:WuChien-HuangCH,
pubmed-author:YehTeng-KuangTK,
pubmed-author:YehYen-NanYN
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pubmed:issnType |
Electronic
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pubmed:day |
23
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4496-510
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pubmed:meshHeading |
pubmed-meshheading:19530697-Animals,
pubmed-meshheading:19530697-Anti-Obesity Agents,
pubmed-meshheading:19530697-Cell Line,
pubmed-meshheading:19530697-Diabetes Mellitus,
pubmed-meshheading:19530697-Diet,
pubmed-meshheading:19530697-Drug Discovery,
pubmed-meshheading:19530697-Drug Inverse Agonism,
pubmed-meshheading:19530697-Eating,
pubmed-meshheading:19530697-Humans,
pubmed-meshheading:19530697-Imidazoles,
pubmed-meshheading:19530697-Inhibitory Concentration 50,
pubmed-meshheading:19530697-Male,
pubmed-meshheading:19530697-Mice,
pubmed-meshheading:19530697-Mice, Obese,
pubmed-meshheading:19530697-Rats,
pubmed-meshheading:19530697-Receptor, Cannabinoid, CB1,
pubmed-meshheading:19530697-Receptor, Cannabinoid, CB2,
pubmed-meshheading:19530697-Substrate Specificity,
pubmed-meshheading:19530697-Thiones
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pubmed:year |
2009
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pubmed:articleTitle |
Discovery of 2-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1H-pyrazol-3-yl]-1,5,5-trimethyl-1,5-dihydro-imidazol-4-thione (BPR-890) via an active metabolite. A novel, potent and selective cannabinoid-1 receptor inverse agonist with high antiobesity efficacy in DIO mice.
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pubmed:affiliation |
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan, ROC.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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