Aggrecanase-1 and -2 (ADAMTS-4 and ADAMTS-5) are zinc metalloproteases involved in the degradation of aggrecan in cartilage. Inhibitors could provide a means of altering the progression of osteoarthritis. We report the identification of 7 which had good oral pharmacokinetics in rats and showed efficacy in a rat chemical model of osteoarthritis. The projected human dose required to achieve sustained plasma levels ≥10 times the hADAMTS-5 IC₅₀ is 5 mg q.d.

中文翻译：

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高选择性人类剂量的乙内酰脲酶Aggrecanase-1和Aggrecanase-2的乙内酰脲抑制剂。

Aggrecanase-1和-2（ADAMTS-4和ADAMTS-5）是锌金属蛋白酶，参与软骨中聚集蛋白聚糖的降解。抑制剂可以提供改变骨关节炎进展的手段。我们报告鉴定7在大鼠中具有良好的口服药代动力学，并在大鼠骨关节炎的化学模型中显示出功效。达到持续血浆水平≥hADAMTS-5 IC ₅₀的10倍所需的预计人体剂量为5 mg qd