咪唑并吡啶类外周苯二氮卓受体配体的合成新方法

A Novel Process for Synthesis of Imidazo-[1,2-a] Pyridine Ligand as the Peripheral Benzodiazepine Receptors

目的咪唑并[1,2-a]吡啶类PBR配体新的合成方法及其同位素125I-标记。方法非放射活性的咪唑并[1,2-a]吡啶通过5-氯-2-氨基吡啶与溴代酮酯缩合后再酰胺化而得。起始溴代酮酯经付-克酰化、酯化和溴代而被制备。放射标记的125I-咪唑并[1,2-a]吡啶通过Na125I在氯胺T反应体系中经碘脱锡交换反应被制备。由反向HPLC纯化得125I-咪唑并[1,2-a]吡啶。结果非放射活性的咪唑并[1,2-a]吡啶6步合成总收率25.2%,放化得率68%,放化纯度大于98%。结论咪唑并[1,2-a]吡啶类PBR配体的合成和标记方法简便,且回收率高。

Objective A novel process for synthesis of substituted imidazo-[ 1,2-a] pyridine and iodine-125 labelling as potential probes for the study of the peripheral benzodiazepine receptors was illustrated. Methods Non-radioactive imidazo-[ 1,2-a] pyridine was synthesized by condensation of 5-chloro-2-aminopyridines with the bromo keto esters and dialkylamines. The starting bromo keto esters were prepared by Friedel-Crafts acylation, esters and bromination. Radiolabelling ^125I-imidazo-[ 1, 2-a] pyridines was prepared by iododestannylation with Na ^125I in the presence of chloramine-T and purified by C18 reverse phase HPLC. Results Non-radioactlve imidazo-[ 1, 2-a] pyridine was synthesized in a total yield of 25.2%. Radiolabelling ^125I-imidazo-[ 1,2-a] pyridines was prepared in 68% radiochemical yield and over 98% radiochemical purity. Conclusion This novel process for preparation and radiosynthesis of imidazo-[ 1,2-a]-pyridine-3-acetamides are simple and with high recovery rate.