Advances Toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT(1A) receptor antagonism/SSRI activities. Part 2.
Potent 5-HT1A/SSRIs at low nanomolar and subnanomolar concentrations were identified in a series of 1-(1H-indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols. Incorporation of an alpha-Me group in the piperidine ring with its specific stereochemistry enhanced binding affinity at the 5-HT reuptake site and in vitro 5-HT(1A) antagonist functional activity.
Takeuchi
Kumiko
K
Lilly Research Laboratories, A Division of Eli Lilly and Company, IN 46285, Indianapolis, USA. ktak@lilly.com
Kohn
Todd J
TJ
Honigschmidt
Nicholas A
NA
Rocco
Vincent P
VP
Spinazze
Patrick G
PG
Koch
Daniel J
DJ
Atkinson
Steven T
ST
Hertel
Larry W
LW
Nelson
David L
DL
Wainscott
D Bradley
DB
Ahmad
Laura J
LJ
Shaw
Janice
J
Threlkeld
Penny G
PG
Wong
David T
DT
D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007202:Indicators and Reagents; D017374:Paroxetine / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D020005:Propanols / Q000138:chemical synthesis* / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007202:Indicators and Reagents; D017374:Paroxetine; D010880:Piperidines; D020005:Propanols; D044282:Receptor, Serotonin, 5-HT1A; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors