Cathepsins have emerged as important targets in various tissues degenerative disorders due to their involvement in degradation of extracellular matrices and endogenous protein turnover. Elevated cathepsins levels vis-à-vis decreased concentration of endogenous inhibitors has been reported at different diseased sites. The design and synthesis of specific potential anti-cathepsin agents is therefore of great significance. Most of potential anti-cathepsin agents developed have peptide based structures with an active warhead. Due to oral instability and immunogenic problems related to peptidyl inhibitors drift the synthesis and evaluation of non-peptide cathepsin inhibitors in last two decades. The present work provides a detailed structure activity relationship for developing potential non-peptide anticathepsin agents based on in-vitro inhibition studies of a library of synthesized thiocarbamoyl- non-peptide inhibitors.

由于组织蛋白酶参与细胞外基质的降解和内源性蛋白质更新，它们已成为各种组织退行性疾病的重要靶标。据报道，在不同的患病部位，组织蛋白酶水平相对于内源性抑制剂浓度降低而升高。因此，特定潜在抗组织蛋白酶剂的设计和合成具有重要意义。开发的大多数潜在的抗组织蛋白酶药物都具有带有主动弹头的基于肽的结构。由于口服不稳定和与肽基抑制剂有关的免疫原性问题，近二十年来非肽组织蛋白酶抑制剂的合成和评估。本工作提供了一种详细的结构活性关系，用于开发基于以下方面的潜在非肽抗组织蛋白酶药物合成的硫代氨基甲酰基非肽抑制剂文库的体外抑制研究。