A New Synthesis of 4, 4-Diaryl/Diheteroaryl-3-butenyl Derivatives of Nipecotic Acids as GABA Transporter Inhibitors

A New Synthesis of 4, 4-Diaryl/Diheteroaryl-3-butenyl Derivatives of Nipecotic Acids as GABA Transporter Inhibitors

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摘要 A new method for the synthesis of 4, 4-diaryl/diheteroaryl-3-butenyl derivatives of nipecotic acid as GABA transporter inhibitors is described. The key intermediates 4-tosyl-1, 1-diaryl/diheteroaryl-1-butene 10a-d were synthesized by Wittig reaction, and followed by alkylation with （R）-3-piperidinecarboxylate. The resulting N-cycloalkylated amino acid esters 11a-d were saponified and then acidified to get the target compounds 1a-d. The preliminary bioassays showed that la-d exhibited excellent inhibition of [3H]-GABA uptake in vitro of culture cells. A new method for the synthesis of 4, 4-diaryl/diheteroaryl-3-butenyl derivatives of nipecotic acid as GABA transporter inhibitors is described. The key intermediates 4-tosyl-1, 1-diaryl/diheteroaryl-1-butene 10a-d were synthesized by Wittig reaction, and followed by alkylation with （R）-3-piperidinecarboxylate. The resulting N-cycloalkylated amino acid esters 11a-d were saponified and then acidified to get the target compounds 1a-d. The preliminary bioassays showed that la-d exhibited excellent inhibition of [3H]-GABA uptake in vitro of culture cells.

作者 Jian Ge ZHANG Chang Sheng JIANG Guo Qiang LIN Ren WEN

机构地区 Department of Medicinal Chemistry Shanghai Institute of Organic Chemistry

出处《Chinese Chemical Letters》 SCIE CAS CSCD 2005年第9期1205-1208,共4页 中国化学快报（英文版）

关键词 Tiagabine nipecotic acid DERIVATIVES synthesis GABA transporter inhibitor Tiagabine, nipecotic acid, derivatives, synthesis, GABA transporter inhibitor

分类号 O626 [理学—有机化学]

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Chinese Chemical Letters

2005年第9期

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A New Synthesis of 4, 4-Diaryl/Diheteroaryl-3-butenyl Derivatives of Nipecotic Acids as GABA Transporter Inhibitors

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