5′-Methylthioadenosine (MTA) is a natural substrate of MTA phosphorylase (MTAP) and is converted to adenine via a salvage pathway for AMP production in normal healthy cells. The lack of MTAP expression in many solid tumors and hematologic malignancies compared to normal healthy cells has been explored in a potential therapeutic strategy to selectively target tumor cells using antimetabolites such as 5-fluorouracil (5-FU) and 6-thioguanine (6-TG) while protecting normal healthy cells with MTA. Herein, a series of carbamate prodrugs, namely the N-(alkyloxy)carbonyl-MTA derivatives 2a-f, was designed, synthesized, and evaluated as potential prodrugs of MTA. All carbamate prodrugs were stable in phosphate buffer, pH 7.4 at 37 °C. In the presence of mouse liver microsomes, the prodrugs were converted to MTA at varying rates with the hexyl and butyl carbamates 2a and 2b most readily activated (t_1/2 of 1.2 and 9.4 h, respectively). The activation was shown to be mediated by carboxyesterases present in mouse liver microsomes.

5'-甲硫基腺苷（MTA）是MTA磷酸化酶（MTAP）的天然底物，可通过挽救途径转化为腺嘌呤，以在正常健康细胞中产生AMP。与正常健康细胞相比，在许多实体瘤和血液系统恶性肿瘤中缺乏MTAP表达已被研究为一种潜在的治疗策略，可使用抗代谢物（例如5-氟尿嘧啶（5-FU）和6-硫鸟嘌呤（6-TG）选择性靶向肿瘤细胞），同时使用MTA保护正常的健康细胞。在此，一系列氨基甲酸酯前药，即N-（烷氧基）羰基-MTA衍生物2a-f被设计，合成和评估为MTA的潜在前药。所有氨基甲酸酯前药在37°C的pH 7.4磷酸盐缓冲液中均稳定。在小鼠肝微粒体存在下，前药以不同的速率转化为MTA，氨基甲酸己酯和氨基甲酸丁酯2a和2b最容易活化（分别为t _1/2的1.2和9.4 h）。显示该活化是由小鼠肝微粒体中存在的羧酯酶介导的。