Discovery of benzhydrylpiperazine derivatives as CB1 receptor inverse agonists via privileged structure-based approach.
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Meng T, Wang J, Peng H, Fang G, Li M, Xiong B, Xie X, Zhang Y, Wang X, Shen J
Discovery of benzhydrylpiperazine derivatives as CB1 receptor inverse agonists via privileged structure-based approach.
Eur J Med Chem. 2010 Mar;45(3):1133-9. doi: 10.1016/j.ejmech.2009.12.018. Epub 2009 Dec 16.
- PubMed ID
- 20047779 [ View in PubMed]
- Abstract
The present study describes the identification via privileged structure-based approach of the benzhydrylpiperazine moiety as a potential scaffold to develop novel CB(1) receptor modulators. Efficient structural optimization of the initial four hit compounds led to a high quality lead series, represented by compound 6c. Compound 6c is a highly potent and selective CB(1) receptor inverse agonist that is able to reduce body weight in diet-induced obese Sprague-Dawley rats. The preparation of privileged structure-based library, the progression from hit to lead, the structure-activity relationships in the lead series and in vitro and in vivo activity of compound 6c are discussed.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Rimonabant Cannabinoid receptor 1 Ki (nM) 0.74 N/A N/A Details Rimonabant Cannabinoid receptor 1 IC 50 (nM) 3.2 N/A N/A Details Rimonabant Cannabinoid receptor 1 EC 50 (nM) 0.11 N/A N/A Details