Research article summary (published 11 Aug 2009):

Synthesis, potency, and in vivo evaluation of 2-piperazin-1-ylquinoline analogues as dual serotonin reuptake inhibitors and serotonin 5-HT1A receptor antagonists.

Full Abstract

On the basis of the previously reported clinical candidate, SSA-426 (1), a series of related 2-piperazin-1-ylquinoline derivatives 3-16 were synthesized and evaluated as dual-acting serotonin (5-HT) reuptake inhibitors and 5-HT1A receptor antagonists. In particular, compound 7 exhibits potent functional activities at both the 5-HT transporter and 5-HT1A receptor, good selectivity over the alpha1-adrenergic and dopaminergic receptors, acceptable pharmacokinetic properties, and a favorable in vivo profile.

Author information

Author/s: Zhou, Dahui (D); Stack, Gary P (GP); Lo, Jennifer (J); Failli, Amedeo A (AA); Evrard, Deborah A (DA); Harrison, Boyd L (BL); Hatzenbuhler, Nicole T (NT); Tran, Megan (M); Croce, Susan (S); Yi, Soo (S); Golembieski, Jeannette (J); Hornby, Geoffrey A (GA); Lai, Margaret (M); Lin, Qian (Q); Schechter, Lee E (LE); Smith, Deborah L (DL); Shilling, Adam D (AD); Huselton, Christine (C); Mitchell, Paul (P); Beyer, Chad E (CE); Andree, Terrance H (TH);

Affiliation: Chemical Sciences, Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA. zhoud(-atsign-)wyeth.com

Journal and publication information

Publication Type: Journal Article

Journal: Journal of medicinal chemistry (J Med Chem), published in United States. (Language: eng)

Reference: 2009-Aug; vol 52 (issue 15) : pp 4955-9

Dates: Created 2009/09/01; Completed 2009/09/21;

PMID: 19719241, status: MEDLINE (last retrieval date: 9/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Antidepressive Agents - pharmacology CHO Cells Cricetinae Cricetulus Cytochrome P-450 Enzyme System - antagonists & inhibitors Humans Microdialysis Piperazines - chemical synthesis; pharmacology

Piperazines - chemical synthesis; pharmacology Quinolines - chemical synthesis; pharmacology Rats Receptor, Serotonin, 5-HT1A - antagonists & inhibitors Receptors, Adrenergic, alpha-1 - metabolism Receptors, Dopamine - metabolism Serotonin Antagonists - chemical synthesis; pharmacokinetics; pharmacology Serotonin Uptake Inhibitors - chemical synthesis; pharmacokinetics; pharmacology Structure-Activity Relationship

Associated Chemicals: Antidepressive Agents (0) ; Piperazines (0) ; Quinolines (0) ; Receptors, Adrenergic, alpha-1 (0) ; Receptors, Dopamine (0) ; Serotonin Antagonists (0) ; Serotonin Uptake Inhibitors (0) ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; Cytochrome P-450 Enzyme System (9035-51-2)

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