Discovery of novel orally active ureido NPY Y5 receptor antagonists

We have derived a novel series of neuropeptide Y (NPY) Y5 receptor antagonists from the biphenylurea 3. Cyclohexylurea 21c, a member of the series, is a potent NPY Y5 receptor antagonist that exhibits excellent pharmacokinetic parameters in rats and dogs. On chronic oral administration to diet-induced obese rats, 21c displayed an anti-obesity profile, causing a modest reduction in food intake, a significant decrease in body weight gain, a decrease in adipose mass, and an increase in lean tissue mass.

Structure–activity relationship studies leading to the potent, selective NPY Y5 receptor antagonist 21c are described. Compound 21c demonstrated dose-dependent anti-obesity effects in diet-induced obese rats after chronic oral administration.Figure optionsDownload as PowerPoint slide