Design, synthesis, and evaluation of inhibitors of cathepsin L: Exploiting a unique thiocarbazate chemotype

组织蛋白酶L抑制剂的设计、合成和评价:利用独特的硫代氨基甲酸酯化学类型

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Abstract

Recently, we identified a thiocarbazate that exhibits potent inhibitory activity against human cathepsin L. Since this structure represents a novel chemotype with potential for activity against the entire cysteine protease family, we designed, synthesized, and assayed a series of analogs to probe the mechanism of action, as well as the structural requirements for cathepsin L activity. Molecular docking studies using coordinates of a papain-inhibitor complex as a model for cathepsin L provided useful insights.

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