5HT₆ receptor antagonists: a patent update. Part 1. Sulfonyl derivatives

Abstract

Introduction: Among a variety of proteins included in a relatively wide GPCR family, serotonin 5HT receptors (5HT₆Rs) are highly attractive as important biological targets with enormous clinical importance. Among this subclass, 5HT₆R is the most recently discovered group. Available biological data clearly indicate that 5HT₆R antagonists can be used as effective regulators in a variety of contexts, including memory formation, age-related cognitive impairments and memory deficits associated with conditions such as schizophrenia, Parkinson's disease and Alzheimer's disease. Therefore, this receptor has already attracted a considerable attention within the scientific community, due to its versatile therapeutic potential.

Areas covered: The current paper is an update to the comprehensive review article published previously in Expert Opinion on Therapeutic Patents (see issue 20(7), 2010). Here, the main focus is on small-molecule compounds – 5HT₆ antagonists – which have been described in recent patent literature, since the end of 2009. To obtain a clear understanding of the situation and dynamic within the field of 5HT₆ ligands, having an obvious pharmaceutical potential in terms of related patents, a comprehensive search through several key patent collections have been provided. The authors describe the reported chemical classes and scaffolds in sufficient detail to provide a valuable insight in the 5HT₆R chemistry and pharmacology. The review consists of two core parts with separate sections arranged in accordance with the main structural features of 5HT₆R ligands.

Expert opinion: Recent progress in the understanding of the 5HT₆ receptor function and structure includes a suggested constitutive activity for the receptor, development of a number of multimodal small molecule ligands and re-classification of many selective antagonists as pseudo-selective agents. Heterocycles with sulfonyl group and without any basic center provide sufficient supramolecular interactions and show high antagonistic activity against 5HT₆R.

Keywords::

• 5HT₆R
• Alzheimer's disease
• antagonists
• depression
• Huntington's disease
• ligands
• obesity
• schizophrenia
• serotonin receptors

Acknowledgement

The authors would like to extend their sincere gratitude to SE Tkachenko, IM Okun and MG Kadieva for invaluable help during the manuscript preparation.

Notes