基于氮杂环庚酮的人组织蛋白酶 S 抑制剂：通过 P2 取代基优化选择性。
Azepanone-based inhibitors of human cathepsin S: optimization of selectivity via the P2 substituent.
机构信息
GlaxoSmithKline, King of Prussia, PA 19406, United States.
出版信息
Bioorg Med Chem Lett. 2011 Aug 1;21(15):4409-15. doi: 10.1016/j.bmcl.2011.06.045. Epub 2011 Jun 17.
PMID:21733692
Abstract
A series of azepanone inhibitors of cathepsin S is described. Selectivity over both cathepsin K and cathepsin L was achieved by varying the P2 substituent. Ultimately, a balanced potency and selectivity profile was achieved in compound 39 possessing a 1-methylcyclohexyl alanine at P2 and nicotinamide as the P' substituent. The cellular potency of selected analogs is also described.
摘要
本文描述了一系列作为组织蛋白酶 S 的氮杂环庚酮抑制剂。通过改变 P2 取代基，可以实现对组织蛋白酶 K 和 L 的选择性。最终，在 P2 位含有 1-甲基环己基丙氨酸且 P' 取代基为烟酰胺的化合物 39 中实现了平衡的效力和选择性。还描述了所选类似物的细胞效力。
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