The discovery and SAR of indoline-3-carboxamides--a new series of 5-HT6 antagonists

Mark Reid; Ian Carlyle; Wilson L Caulfield; Tom R Clarkson; Fiona Cusick; Ola Epemolu; Robert Gilfillan; Richard Goodwin; David Jaap; Elise C O'Donnell; Jeremy Presland; Zoran Rankovic; Daniel Spinks; Gayle Spinks; Anne M Thomson; Fiona Thomson; James Strain; Grant Wishart

doi:10.1016/j.bmcl.2010.04.085

The discovery and SAR of indoline-3-carboxamides--a new series of 5-HT6 antagonists

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3713-6. doi: 10.1016/j.bmcl.2010.04.085. Epub 2010 Apr 24.

Authors

Mark Reid¹, Ian Carlyle, Wilson L Caulfield, Tom R Clarkson, Fiona Cusick, Ola Epemolu, Robert Gilfillan, Richard Goodwin, David Jaap, Elise C O'Donnell, Jeremy Presland, Zoran Rankovic, Daniel Spinks, Gayle Spinks, Anne M Thomson, Fiona Thomson, James Strain, Grant Wishart

Affiliation

¹ Department of Chemistry, Schering-Plough Research Institute, Newhouse, Lanarkshire, UK. [email protected]

PMID: 20471831
DOI: 10.1016/j.bmcl.2010.04.085

Abstract

Antagonists of the 5-HT(6) receptor have been shown to improve cognitive function in a wide range of animal models and as such may prove to be attractive agents for the symptomatic treatment of cognitive disorders such as Alzheimer's disease (AD) and schizophrenia. We report herein the identification and SAR around N-(2-aminoalkyl)-1-(arylsulfonyl)indoline-3-carboxamides-a novel chemotype of 5-HT(6) antagonists.

MeSH terms

Amides / chemistry*
Amides / pharmacology
Animals
Biological Availability
Drug Discovery
Humans
Indoles / chemistry*
Indoles / pharmacology
Male
Microsomes
Pharmacokinetics
Rats
Rats, Wistar
Receptors, Serotonin / drug effects*
Serotonin Receptor Agonists / chemical synthesis*
Serotonin Receptor Agonists / chemistry
Structure-Activity Relationship

Substances

Amides
Indoles
Receptors, Serotonin
Serotonin Receptor Agonists
serotonin 6 receptor
indoline