title: Synthesis, potency, and in vivo evaluation of 2-piperazin-1-ylquinoline analogues as dual serotonin reuptake inhibitors and serotonin 5-HT1A receptor antagonists.
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.
authors.affiliation: Chemical Sciences, Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA. zhoud@wyeth.com
authors.forename: Dahui
authors.initials: D
authors.lastname: Zhou
authors.forename: Gary P
authors.initials: GP
authors.lastname: Stack
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lo
authors.forename: Amedeo A
authors.initials: AA
authors.lastname: Failli
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Evrard
authors.forename: Boyd L
authors.initials: BL
authors.lastname: Harrison
authors.forename: Nicole T
authors.initials: NT
authors.lastname: Hatzenbuhler
authors.forename: Megan
authors.initials: M
authors.lastname: Tran
authors.forename: Susan
authors.initials: S
authors.lastname: Croce
authors.forename: Soo
authors.initials: S
authors.lastname: Yi
authors.forename: Jeannette
authors.initials: J
authors.lastname: Golembieski
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Hornby
authors.forename: Margaret
authors.initials: M
authors.lastname: Lai
authors.forename: Qian
authors.initials: Q
authors.lastname: Lin
authors.forename: Lee E
authors.initials: LE
authors.lastname: Schechter
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Smith
authors.forename: Adam D
authors.initials: AD
authors.lastname: Shilling
authors.forename: Christine
authors.initials: C
authors.lastname: Huselton
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Chad E
authors.initials: CE
authors.lastname: Beyer
authors.forename: Terrance H
authors.initials: TH
authors.lastname: Andree
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D065607:Cytochrome P-450 Enzyme Inhibitors; D006801:Humans; D017551:Microdialysis; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D010879:Piperazines; D011804:Quinolines; D018340:Receptors, Adrenergic, alpha-1; D011954:Receptors, Dopamine; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors