Recent progress in the discovery of melanin-concentrating hormone 1-receptor antagonists

The appetite stimulating effects of melanin-concentrating hormone (MCH) continues to be of high interest, and there is substantial support to investigate the use of MCH 1-receptor antagonists for the treatment of obesity. Other areas of potential use for MCH 1-receptor antagonists include depression and anxiety. There are, to date, no clinical proof of concept data, and efforts are ongoing for the discovery of novel MCH 1-receptor antagonists, as evidenced by the number of patent applications published over the last 5 years.

This review covers the patent literature on MCH 1-receptor antagonists from January 2006 to November 2010. The emphasis is on disclosed biological data, especially in vivo data, of exemplified compounds. Wherever possible, selectivity towards undesired pharmacology is analysed.

Over the years, different approaches have been taken to overcome the undesired effects of MCH 1-receptor antagonists, such as interactions with the hERG channel. Many programmes have faced difficulties and, to date, only a few compounds have progressed into humans. From this point of view, the MCH 1-receptor is regarded as a difficult target, and whether newer programmes will be successful depends, to a large extent, on their selectivity.