Design, synthesis, and biological evaluation of the N-diarylalkenyl-piperidinecarboxylic acid derivatives as GABA uptake inhibitors (I).
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.
Zheng
Jianbin
J
Department of Medicinal Chemistry, Fudan University, Shanghai 200032, China.
Wen
Ren
R
Luo
Xiaomin
X
Lin
Guoqiang
G
Zhang
Jiange
J
Xu
Linfeng
L
Guo
Lihe
L
Jiang
Hualiang
H
D000818:Animals; D001692:Biological Transport; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D018755:GABA Agonists / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D009474:Neurons / Q000378:metabolism; D009557:Nipecotic Acids / Q000737:chemistry / Q000494:pharmacology; D010875:Pipecolic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000493:pharmacokinetics
D002264:Carboxylic Acids; D018755:GABA Agonists; D009557:Nipecotic Acids; D010875:Pipecolic Acids; D005680:gamma-Aminobutyric Acid; D000078308:Tiagabine