title: Advances Toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT(1A) receptor antagonism/SSRI activities. Part 2.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, A Division of Eli Lilly and Company, IN 46285, Indianapolis, USA. ktak@lilly.com
authors.forename: Kumiko
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Kohn
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Honigschmidt
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Rocco
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Spinazze
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Koch
authors.forename: Steven T
authors.initials: ST
authors.lastname: Atkinson
authors.forename: Larry W
authors.initials: LW
authors.lastname: Hertel
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: D Bradley
authors.initials: DB
authors.lastname: Wainscott
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Ahmad
authors.forename: Janice
authors.initials: J
authors.lastname: Shaw
authors.forename: Penny G
authors.initials: PG
authors.lastname: Threlkeld
authors.forename: David T
authors.initials: DT
authors.lastname: Wong
mesh_terms: 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
chemical_list: 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