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Bioorg Med Chem Lett. 2009 Sep 1;19(17):5078-81. doi: 10.1016/j.bmcl.2009.07.049. Epub 2009 Jul 31.

N-[(3S)-Pyrrolidin-3-yl]benzamides as novel dual serotonin and noradrenaline reuptake inhibitors: impact of small structural modifications on P-gp recognition and CNS penetration.

Author information

1
Department of Genitourinary Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent, UK. florian.wakenhut@pfizer.com

Erratum in

  • Bioorg Med Chem Lett. 2010 Jan 15;20(2):772. Ryckmans, Thomas [added].

Abstract

The structure-activity relationship and the synthesis of novel N-[(3S)-pyrrolidin-3-yl]benzamides as dual serotonin and noradrenaline monoamine reuptake inhibitors (SNRI) is described. Preferred compound 9 aka PF-184,298 is a potent SNRI with good selectivity over dopamine reuptake inhibition (DRI), good in vitro metabolic stability, weak CYP inhibition and drug-like physicochemical properties consistent with CNS target space. Evaluation in an in vivo preclinical model of stress urinary incontinence showed 9 significantly increased urethral tone at free plasma concentrations consistent with its in vitro primary pharmacology.

PMID:
19647430
DOI:
10.1016/j.bmcl.2009.07.049
[Indexed for MEDLINE]

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