title: 5HT(6) receptor antagonists: a patent update. Part 1. Sulfonyl derivatives.
abstract: BACKGROUND
  Among a variety of proteins included in a relatively wide GPCR family, serotonin 5HT receptors (5HT(6)Rs) are highly attractive as important biological targets with enormous clinical importance. Among this subclass, 5HT(6)R is the most recently discovered group. Available biological data clearly indicate that 5HT(6)R 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.
  
  
  METHODS
  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 - 5HT(6) 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 5HT(6) 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 5HT(6)R chemistry and pharmacology. The review consists of two core parts with separate sections arranged in accordance with the main structural features of 5HT(6)R ligands.
  
  
  CONCLUSIONS
  Recent progress in the understanding of the 5HT(6) 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 5HT(6)R.
authors: ChemDiv, Inc., 6605 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors: Alexandre V
authors: AV
authors: Ivachtchenko
authors: Yan A
authors: YA
authors: Ivanenkov
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D007880:Legislation, Drug; D008024:Ligands; D015394:Molecular Structure; D010330:Patents as Topic; D011487:Protein Conformation; D011985:Receptors, Serotonin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013450:Sulfones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002491:Central Nervous System Agents; D008024:Ligands; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013450:Sulfones; C097216:serotonin 6 receptor