5-HT2C receptor modulators: a patent survey

Abstract

Importance of the field: The 5-HT_2C receptor is a GPCR and is one of the 14 subtypes that constitute the serotonin receptor family. The 5-HT_2C receptor is exclusively expressed in the CNS where it demonstrates a wide distribution and displays high-affinity interactions with a wide variety of psychiatric medications. Modulators of 5-HT_2C have been implicated as a potential treatment for diseases of significant unmet medical need, including obesity, schizophrenia, depression, anxiety, Parkinson's disease, drug addiction, erectile dysfunction and urinary incontinence. Thus, there is a great interest in developing potent and selective 5-HT_2C receptor modulators.

Areas covered in this review: This review article highlights the research progress in 5-HT_2C receptor modulators published in the patent literature between January 2003 and June 2010, giving emphasis to the medicinal chemist's standpoint.

What the reader will gain: Readers will rapidly gain an overview of the various 5-HT_2C receptor modulators reported in the patent literature in the past 8 years. Furthermore, the readers will learn which structure type can interact with the 5-HT_2C receptor. In addition, the readers will be aware of the pharmaceutical companies that have been the main players in the field.

Take home message: There is substantial evidence supporting the concept that a selective 5-HT_2C receptor modulator should provide benefit in the treatment of a variety of CNS disorders. Although research efforts have identified several promising 5-HT_2C receptor modulators that display high functional selectivity, further clinical efficacy and safety data are needed to prove their actual clinical utility. Therefore, the query for selectively acting 5-HT_2C receptor modulators is still ongoing.

Keywords::

• 5-HT
• 5-HT_2C receptor
• 5-HT_2C receptor agonist
• 5-HT_2C receptor antagonist
• 5-HT_2C receptor inverse agonist
• 5-HT_2C receptor modulator
• anxiety
• depression
• drug addiction
• erectile dysfunction
• lorcaserin
• obesity
• Parkinson's disease
• schizophrenia
• urinary incontinence
• vabicaserin

Acknowledgements

The authors thank J Kim for his scientific discussions regarding small molecule programs at Green Cross Corp. (GCC). The authors also thank EC Huh for his support for R&D at GCC.

Notes

This box summarizes key points contained in the article.