Study on Medicinal Chemistry of Reversible Cysteine Protease Inhibitors for the Treatment of Infectious Diseases

本工作描述了基于芳基酮结构的半胱氨酸蛋白酶抑制剂开发的通用方法的建立。作为一个例子，从我们的初步抑制剂具有温和的活性，我们开发了有效的三肽和二肽型SARS-CoV 3CL蛋白酶抑制剂。结果表明，我们的芳基酮策略在病毒半胱氨酸蛋白酶抑制剂的开发中有效。此外，我们开发了一种固相试剂，可以通过非常简单的程序将生物素引入到靶分子中，以获得高亲和力的底物，该底物可以通过引入芳基酮结构而变成有效的抑制剂。

This work describes the establishment of common method for the development of cysteine protease inhibitors based on the aryl-ketone structure. As an example, from our preliminary inhibitor with a mild activity, we developed potent tri- and di-peptide-type SARS-CoV 3CL protease inhibitors. The results suggested that our aryl-ketone strategy worked effectively in the development of viral cysteine protease inhibitors. In addition, we developed a solid phase reagent that can introduce biotin to the target molecules by a very simple procedure in order to obtain a high affinity substrate, which can be changeable to the potent inhibitor by introducing the aryl-ketone structure.