Studies on the structure-activity relationship of bicifadine analogs as monoamine transporter inhibitors

Mingzhu Zhang; Florence Jovic; Troy Vickers; Brian Dyck; Junko Tamiya; Jonathan Grey; Joe A Tran; Beth A Fleck; Rebecca Pick; Alan C Foster; Chen Chen

doi:10.1016/j.bmcl.2008.05.077

Studies on the structure-activity relationship of bicifadine analogs as monoamine transporter inhibitors

Bioorg Med Chem Lett. 2008 Jul 1;18(13):3682-6. doi: 10.1016/j.bmcl.2008.05.077. Epub 2008 May 23.

Authors

Mingzhu Zhang¹, Florence Jovic, Troy Vickers, Brian Dyck, Junko Tamiya, Jonathan Grey, Joe A Tran, Beth A Fleck, Rebecca Pick, Alan C Foster, Chen Chen

Affiliation

¹ Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.

PMID: 18539031
DOI: 10.1016/j.bmcl.2008.05.077

Abstract

Compounds with various activities and selectivities were discovered through structure-activity relationship studies of bicifadine analogs as monoamine transporter inhibitors. The norepinephrine-selective 2-thienyl compound S-6j was efficacious in a rodent pain model.

MeSH terms

Animals
Bridged Bicyclo Compounds, Heterocyclic / chemistry*
Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
Caco-2 Cells
Chemistry, Pharmaceutical / methods
Drug Design
Humans
Inhibitory Concentration 50
Membrane Transport Proteins / chemistry
Membrane Transport Proteins / pharmacology
Models, Chemical
Neurotransmitter Agents / metabolism
Neurotransmitter Transport Proteins / antagonists & inhibitors
Neurotransmitter Transport Proteins / chemistry*
Norepinephrine / chemistry
Pain
Rats
Structure-Activity Relationship

Substances

Bridged Bicyclo Compounds, Heterocyclic
Membrane Transport Proteins
Neurotransmitter Agents
Neurotransmitter Transport Proteins
bicifadine
Norepinephrine