氯沙坦的合成工艺研究进展

Progress in the Synthetic Process of Losartan

摘要:

氯沙坦为口服非肽类血管紧张素Ⅱ受体拮抗剂，于1994年首次在瑞典上市，并于2004年获得美国食品与药物管理局（FDA）批准，近年来一直是临床治疗高血压的一线药物。氯沙坦由咪唑环片断（A）、苯环片断（B）和（C）以及四氮唑环片断（D）拼合而成。本文根据各片断的连接次序不同，将氯沙坦的合成策略分为如下五种：“(B C) D A”策略，“(B C) A D”策略，“(C D) B A”策略，“(C D) (A B)策略”和“(A B) C D”策略。本文以这五种策略为主线综述了氯沙坦自诞生至今的合成工艺研究进展。

Abstract:

Losartan was the oral non-peptide angiotensin Ⅱ receptor antagonist which was first approved by Sweden in 1994, and then approved by American Food and Drug Administration (FDA) in 2004. In recent years, Losartan has been the first-line antihypertensive drug. Structurally, Losartan was constituted by linking four structural fragment: imidazole ring (A), phenyl ring (B) and (C) as well as tetrazole ring (D). Based on the different linkage order of four ring fragment, the synthetic strategies of Losartan have been divided into five such as (B C) D A, (B C) A D, (C D) B A, (C D) (A B) and (A B) C D. In this paper, the progress in the synthetic process of Losartan has been reviewed from the perspective of five different synthetic strategies since its first discovery.