Discovery of 2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropyl)-6,7-dihydro-2H-pyraz olo[3,4-f][1,4]oxazepin-8(5H)-one (PF-514273), a novel, bicyclic lactam-based cannabinoid-1 receptor antagonist for the treatment of obesity.

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Dow RL, Carpino PA, Hadcock JR, Black SC, Iredale PA, DaSilva-Jardine P, Schneider SR, Paight ES, Griffith DA, Scott DO, O'Connor RE, Nduaka CI

Discovery of 2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropyl)-6,7-dihydro-2H-pyraz olo[3,4-f][1,4]oxazepin-8(5H)-one (PF-514273), a novel, bicyclic lactam-based cannabinoid-1 receptor antagonist for the treatment of obesity.

J Med Chem. 2009 May 14;52(9):2652-5. doi: 10.1021/jm900255t.

PubMed ID
19351113 [ View in PubMed
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Abstract

We report the design, synthesis, and structure-activity relationships of novel bicyclic lactam-based cannabinoid type 1 (CB(1)) receptor antagonists. Members of these series are potent, selective antagonists in in vitro/in vivo efficacy models of CB(1) antagonism and exhibit robust oral activity in rodent models of food intake. These efforts led to the identification of 19d, which has been advanced to human clinical trials for weight management.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
RimonabantCannabinoid receptor 1Ki (nM)1.87.430Details
RimonabantCannabinoid receptor 1EC 50 (nM)1.67.430Details