Synthesis and structure-activity relationship of novel lactam-fused chroman derivatives having dual affinity at the 5-HT(1A) receptor and the serotonin transporter.
The structure-activity relationship (SAR) for three series of lactam-fused chroman derivatives possessing 3-amino substituents was evaluated. Many compounds exhibited affinities for both the 5-HT(1A) receptor and the 5-HT transporter. Compounds 45 and 53 demonstrated 5-HT(1A) antagonist activities in the in vitro cAMP turnover model.
Shen
Zhongqi
Z
Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, United States. shenz@wyeth.com
Siva Ramamoorthy
P
P
Hatzenbuhler
Nicole T
NT
Evrard
Deborah A
DA
Childers
Wayne
W
Harrison
Boyd L
BL
Chlenov
Michael
M
Hornby
Geoffrey
G
Smith
Deborah L
DL
Sullivan
Kelly M
KM
Schechter
Lee E
LE
Andree
Terrance H
TH
D002839:Chromans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015195:Drug Design; D007769:Lactams / Q000737:chemistry*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002839:Chromans; D000242:Cyclic AMP; D007769:Lactams; D044282:Receptor, Serotonin, 5-HT1A; D058829:Serotonin 5-HT1 Receptor Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors