Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors

Puwen Zhang; Eugene A Terefenko; Casey C McComas; Paige E Mahaney; An Vu; Eugene Trybulski; Elizabeth Koury; Grace Johnston; Jenifer Bray; Darlene Deecher

doi:10.1016/j.bmcl.2008.10.026

Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6067-70. doi: 10.1016/j.bmcl.2008.10.026. Epub 2008 Oct 11.

Authors

Puwen Zhang¹, Eugene A Terefenko, Casey C McComas, Paige E Mahaney, An Vu, Eugene Trybulski, Elizabeth Koury, Grace Johnston, Jenifer Bray, Darlene Deecher

Affiliation

¹ Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. ZhangP@wyeth.com

PMID: 18951020
DOI: 10.1016/j.bmcl.2008.10.026

Abstract

A series of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors was discovered. Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxetine and atomoxetine (4 and 5).

MeSH terms

Benzimidazoles / chemical synthesis*
Benzimidazoles / chemistry
Benzimidazoles / pharmacology*
Combinatorial Chemistry Techniques
Drug Design
Humans
Molecular Structure
Neurotransmitter Uptake Inhibitors / chemical synthesis*
Neurotransmitter Uptake Inhibitors / chemistry
Neurotransmitter Uptake Inhibitors / pharmacology*
Norepinephrine / antagonists & inhibitors*
Norepinephrine / metabolism
Stereoisomerism

Substances

Benzimidazoles
Neurotransmitter Uptake Inhibitors
Norepinephrine