Mahajan Pankaj S, Burke Terrence R
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, United States.
Org Process Res Dev. 2023 Apr 20;27(5):847-853. doi: 10.1021/acs.oprd.3c00063. eCollection 2023 May 19.
Dolutegravir (DTG), Bictegravir (BIC), and Cabotegravir (CAB) are the second-generation integrase strand transfer inhibitors (INSTIs) that have been FDA-approved for the treatment of HIV-1 infection. Preparation of these INSTIs utilizes the common intermediate 1-(2,2-dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid (). Presented herein is a literature and patent review of synthetic routes used to access the pharmaceutically important intermediate . The review highlights the ways in which small fine-tuned synthetic modifications have been used to achieve good yields and regioselectivity of ester hydrolysis.
多替拉韦（DTG）、比克替拉韦（BIC）和卡博特韦（CAB）是已获美国食品药品监督管理局（FDA）批准用于治疗HIV-1感染的第二代整合酶链转移抑制剂（INSTIs）。这些INSTIs的制备利用了常见中间体1-(2,2-二甲氧基乙基)-5-甲氧基-6-(甲氧基羰基)-4-氧代-1,4-二氢吡啶-3-羧酸（ ）。本文呈现了用于获取该重要药学中间体的合成路线的文献及专利综述。该综述强调了通过微小精细的合成修饰来实现酯水解的高收率和区域选择性的方法。
