Imidazolylpyrimidine based CXCR2 chemokine receptor antagonists.

An imidazolylpyrimidine was identified in a CXCR2 chemokine receptor antagonist screen and was optimized for potency, in vitro metabolic stability, and oral bioavailability. It was found that subtle structural modification within the series affected the oral bioavailability. Potent and orally available CXCR2 antagonists are herein reported.

The melanocortin receptor MCR4 controls fat consumption.

Melanocortins mediate the effects of leptin in the central nervous system (CNS) and regulate energy balance through the MCR3 and MCR4 receptors. Here, we examined the specific role of MCR4 in modulating fat consumption. In a three-choice feeding model, the non-selective melanocortin agonist MT-II decreased fat consumption preferentially and the effect was absent in mice deficient in MCR4.