选择性内皮素受体阻滞剂darusentan的合成  

Synthesis of darusentan,an ET_A selective endothelin receptor antagonist

作　　者：郭峰[1] 陈益奇[1] 吉民[2] 华维一[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009 [2]东南大学化学化工系,南京210009

出　　处：《中国新药杂志》2005年第2期172-173,共2页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30171078)

摘　　要：目的:合成ET_A选择性内皮素受体阻滞剂darusentan,降低合成的成本和操作难度。方法:以二苯甲酮为原料,经与氯乙酸乙酯在无溶剂的条件下进行Darzens缩合;对甲苯磺酸的催化下醇解;甲基亚硫酸钠的催化下与2-氯-4,6-二甲氧基嘧啶进行亲核取代反应;碱性条件下水解得到目标化合物。结果:目标化合物经红外光谱、核磁共振氢谱、质谱确证其化学结构。结论:该法操作简便,成本低,总收率达53.5%。Objective: To synthesize darusentan, an ET_A selective endothelin receptor antagonist. Methods: Using diphenyl ketone as a starting material, the target compound was synthesized via several steps, involving in non-solvent Darzens condensation with ethyl chloroacetate, methanolysis catalyzed by p-toluene sulfonic acid, nucleophilic substitution with 2-chloro-4, 6-dimethoxypyrimidine catalyzed by sulfinate, and alkaline hydrolysis. Results: The chemical structure of the target compound was verified using IR, ~1H-NMR and MS. Conclusion: The easily controlled and low cost process for the synthesis of darusentan achieved a total yield of 53.5%.

关 键 词：darusentan 药物合成 内皮素受体阻滞剂 

分 类 号：R914.5[医药卫生—药物化学] R972.1[医药卫生—药学]