Discovery of benzhydrylpiperazine derivatives as CB1 receptor inverse agonists via privileged structure-based approach.

Article Details

Citation

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
DrugTargetPropertyMeasurementpHTemperature (°C)
RimonabantCannabinoid receptor 1Ki (nM)0.74N/AN/ADetails
RimonabantCannabinoid receptor 1IC 50 (nM)3.2N/AN/ADetails
RimonabantCannabinoid receptor 1EC 50 (nM)0.11N/AN/ADetails