A concise synthesis of 1,4-dihydro-[1,4]diazepine-5,7-dione, a novel 7-TM receptor ligand core structure with melanocortin receptor agonist activity.

Finding small non-peptide molecules for G protein-coupled receptors (GPCR) whose endogenous ligands are peptides, is a very important task for medicinal chemists. Over the years, compounds mimicking peptide structures have been discovered, and scaffolds emulating peptide backbones have been designed. In our work on GPCR ligands, including cholecystokinin receptor-1 (CCKR-1) agonists, we have employed benzodiazepines as a core structure.

Discovery of small molecule agonists for the bombesin receptor subtype 3 (BRS-3) based on an omeprazole lead.

Starting from a weak omeprazole screening hit, replacement of the pyridine with a 1,3-benzodioxole moiety, modification of the thioether linkage, and substitution of the benzimidazole pharmacophore led to the discovery of nanomolar BRS-3 agonists.

Evidence in female rhesus monkeys (Macaca mulatta) that nighttime caloric intake is not associated with weight gain.

Objective: To evaluate the hypothesis that nighttime consumption of calories leads to an increased propensity to gain weight.

Research Methods And Procedures: Sixteen female rhesus monkeys (Macaca mulatta) were ovariectomized and placed on a high-fat diet to promote weight gain, and we examined whether monkeys that ate a high percentage of calories at night were more likely to gain weight than monkeys that ate the majority of calories during the day.

Results: Within 6 weeks post-ovariectomy, calorie intake and body weight increased significantly (129 +/- 14%, p = 0.

Synthesis and structure activity relationship of guanidines as NPY Y5 antagonists.

A series of bis-aryl substituted guanidines have been discovered as potent NPY Y5 antagonists. The SAR and in vitro metabolic stability of these compounds are discussed.

The role of neuropeptide Y in the ovine fetal cardiovascular response to reduced oxygenation.

This study investigated the role of neuropeptide Y (NPY) in mediating cardiovascular responses to reduced oxygenation in the late gestation ovine fetus by: (1) comparing the effects on the cardiovascular system of an exogenous infusion of NPY with those elicited by moderate or severe reductions in fetal oxygenation; and (2) determining the effect of fetal I.V. treatment with a selective NPY-Y(1) receptor antagonist on the fetal cardiovascular responses to acute moderate hypoxaemia.