Fast Cyclization of a Proline‐Derived Self‐Immolative Spacer Improves the Efficacy of Carbamate Prodrugs
作者:Alberto Dal Corso、Valentina Borlandelli、Cristina Corno、Paola Perego、Laura Belvisi、Luca Pignataro、Cesare Gennari
DOI:10.1002/anie.201916394
日期:2020.3.2
spacers are sophisticated chemical constructs designed for molecular delivery or material degradation. We describe herein a (S)-2-(aminomethyl)pyrrolidine SI spacer that is able to release different types of anticancer drugs (possessing either a phenolic or secondary and tertiary hydroxyl groups) through a fast cyclization mechanism involving carbamate cleavage. The high efficiency of drug release obtained
自焚(SI)间隔基是设计用于分子传递或材料降解的复杂化学结构。我们在本文中描述了(S)-2-(氨基甲基)吡咯烷SI间隔基,其能够通过涉及氨基甲酸酯裂解的快速环化机制释放不同类型的抗癌药物(具有酚或仲和叔羟基基团)。与同类型的常用间隔物相比,发现通过这种间隔物获得的高效药物释放对蛋白酶敏感性前药的体外细胞毒性活性是有益的。这些发现扩大了降解设备的范围,对高效交付平台的未来发展至关重要。