The discovery and SAR of indoline-3-carboxamides--a new series of 5-HT6 antagonists.
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.
Reid
Mark
M
Department of Chemistry, Schering-Plough Research Institute, Newhouse, Lanarkshire, UK. mark.reid@spcorp.com
Carlyle
Ian
I
Caulfield
Wilson L
WL
Clarkson
Tom R
TR
Cusick
Fiona
F
Epemolu
Ola
O
Gilfillan
Robert
R
Goodwin
Richard
R
Jaap
David
D
O'Donnell
Elise C
EC
Presland
Jeremy
J
Rankovic
Zoran
Z
Spinks
Daniel
D
Spinks
Gayle
G
Thomson
Anne M
AM
Thomson
Fiona
F
Strain
James
J
Wishart
Grant
G
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D008861:Microsomes; D010599:Pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000577:Amides; D007211:Indoles; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor; C057812:indoline