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

The present study describes the identification via privileged structure-based approach of the benzhydrylpiperazine moiety as a potential scaffold to develop novel CB1 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 CB1 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.

A series of benzhydrylpiperazine derivatives was identified as a novel class of CB1 receptor inverse agonists utilizing privileged structure approach.Figure optionsDownload as PowerPoint slide