Design, synthesis, and biological evaluation of the N-diarylalkenyl-piperidinecarboxylic acid derivatives as GABA uptake inhibitors (I)

Jianbin Zheng; Ren Wen; Xiaomin Luo; Guoqiang Lin; Jiange Zhang; Linfeng Xu; Lihe Guo; Hualiang Jiang

doi:10.1016/j.bmcl.2005.09.004

Design, synthesis, and biological evaluation of the N-diarylalkenyl-piperidinecarboxylic acid derivatives as GABA uptake inhibitors (I)

Bioorg Med Chem Lett. 2006 Jan 1;16(1):225-7. doi: 10.1016/j.bmcl.2005.09.004. Epub 2005 Oct 21.

Authors

Jianbin Zheng¹, Ren Wen, Xiaomin Luo, Guoqiang Lin, Jiange Zhang, Linfeng Xu, Lihe Guo, Hualiang Jiang

Affiliation

¹ Department of Medicinal Chemistry, Fudan University, Shanghai 200032, China.

PMID: 16246548
DOI: 10.1016/j.bmcl.2005.09.004

Abstract

Twenty novel N-diarylalkenyl-piperidinecarboxylic acid derivatives were synthesized and evaluated as gamma-aminobutyric acid uptake inhibitors. The biological assay showed that (R)-1-[4,4-bis(3-phenoxymethyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic hydrochloride possessed almost as strong GAT1 inhibitory activity as tiagabine. The synthesis and structure-activity relationships are discussed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biological Transport
Carboxylic Acids / chemical synthesis
Carboxylic Acids / chemistry*
Chemistry, Pharmaceutical / methods
Drug Design
Drug Evaluation, Preclinical
GABA Agonists / chemistry
GABA Agonists / pharmacology*
Humans
Inhibitory Concentration 50
Models, Chemical
Neurons / metabolism
Nipecotic Acids / chemistry
Nipecotic Acids / pharmacology
Pipecolic Acids / chemical synthesis
Pipecolic Acids / chemistry*
Structure-Activity Relationship
Tiagabine
gamma-Aminobutyric Acid / metabolism*
gamma-Aminobutyric Acid / pharmacokinetics

Substances

Carboxylic Acids
GABA Agonists
Nipecotic Acids
Pipecolic Acids
gamma-Aminobutyric Acid
Tiagabine