Hongyu Zhao

Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors

A series of structurally novel stearoyl-CoA desaturase1 (SCD1) inhibitors has been identified via molecular scaffold manipulation. Preliminary structure-activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo activity with dose-dependent desaturation index lowering effects.

The prospects of antagonizing the growth hormone secretagogue receptor to treat obesity

Background: Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R) that functions as a short-term meal initiator and a long-term energy balance regulator. Antagonizing GHS-R could be a method to treat obesity. Objective: To review the published in vivo characterization of GHS-R antagonists between 2005 and 2008 and evaluate the validity of antagonizing GHS-R as a therapeutic strategy for obesity. Methods: Primary literature was searched using SciFinder and Google Scholar. Patents were searched using the European Patent Office and SciFinder. Results/conclusion: Several classes of small molecule GHS-R antagonists have been reported to be efficacious in rodent models for weight loss but none has advanced to human clinical trials. Antagonizing GHS-R as a therapy targeting the general obese population is a challenging strategy.