Novel pyridyl-fused 3-amino chroman derivatives with dual action at serotonin transporter and 5-HT1A receptor.
Structural modifications of the initial lead, 3-aminochroman (4), led to the identification of a novel series of pyridyl-fused amino chroman derivatives (5-8) and the structural isomers (9-12). The compounds described were evaluated for dual 5-HT transporter inhibitory and 5-HT(1A) receptor activities. The design strategy, synthesis, and in vitro biological characterization for these novel compounds are described.
Zhou
Dahui
D
Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA. zhoud@wyeth.com
Hatzenbuhler
Nicole T
NT
Gross
Jonathan L
JL
Harrison
Boyd L
BL
Evrard
Deborah A
DA
Chlenov
Michael
M
Golembieski
Jeannette
J
Hornby
Geoffrey
G
Schechter
Lee E
LE
Smith
Deborah L
DL
Andree
Terrance H
TH
Stack
Gary P
GP
D000818:Animals; D002839:Chromans / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D002839:Chromans; D044282:Receptor, Serotonin, 5-HT1A; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors