Synthesis and structure-activity relationship of α-sulfonylhydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis
Synthesis and structure-activity relationship of α-sulfonylhydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis
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DOI：
10.1021/jm0205548
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发表时间：
2003-06-05
影响因子：
7.3
通讯作者：
Cowling, R
中科院分区：
文献类型：
--
作者：
Aranapakam, V;Grosu, GT;Cowling, R
基质金属蛋白酶（MMP）是一类含锌内肽酶，在生理和病理组织降解中发挥关键作用。这些酶受到内源性抑制剂的严格调节，例如 MMP 和 α(2)-巨球蛋白的组织抑制剂。这些酶的过度表达与各种病理性疾病有关，例如关节炎、肿瘤转移、心血管疾病和多发性硬化症。开发有效的小分子抑制剂来调节 MMP 活性是治疗这些退行性疾病的一种方法。目前的工作重点是新型 N-羟基-α-苯磺酰乙酰胺衍生物的发现和 SAR，它们是有效的、选择性的、口服活性的 MMP 抑制剂。
The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. These enzymes are strictly regulated by endogenous inhibitors such as tissue inhibitors of MMPs and alpha(2)-macroglobulins. Overexpression of these enzymes has been implicated in various pathological disorders such as arthritis, tumor metastasis, cardiovascular diseases, and multiple sclerosis. Developing effective small-molecule inhibitors to modulate MMP activity is one approach to treat these degenerative diseases. The present work focuses on the discovery and SAR of novel N-hydroxy-alpha-phenylsulfonylacetamide derivatives, which are potent, selective, and orally active MMP inhibitors.