Abstract
7-Arylsulfonyl substituted benzofuropiperidine was discovered as a novel scaffold for 5HT(6) receptor antagonists. Optimization by substitution at C-1 position led to identification of selective, orally bioavailable, brain penetrant antagonists with reduced hERG liability. An advanced analog tested in rat social recognition model showed significant activity suggesting potential utility in the enhancement of short-term memory.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
-
Animals
-
Benzofurans / chemistry*
-
Brain / embryology
-
Brain / metabolism
-
ERG1 Potassium Channel
-
Ether-A-Go-Go Potassium Channels / metabolism
-
Humans
-
Inhibitory Concentration 50
-
Kinetics
-
Memory, Short-Term / drug effects
-
Models, Chemical
-
Piperidines / chemistry*
-
Rats
-
Receptors, Serotonin / chemistry*
-
Schizophrenia / drug therapy
-
Serotonin Antagonists / pharmacology*
-
Structure-Activity Relationship
Substances
-
Benzofurans
-
ERG1 Potassium Channel
-
Ether-A-Go-Go Potassium Channels
-
KCNH2 protein, human
-
Piperidines
-
Receptors, Serotonin
-
Serotonin Antagonists
-
serotonin 6 receptor
-
piperidine