非环状、口服生物可利用的基于酮的组织蛋白酶K抑制剂。

Acyclic, orally bioavailable ketone-based cathepsin K inhibitors.

作者信息

Barrett David G, Catalano John G, Deaton David N, Long Stacey T, McFadyen Robert B, Miller Aaron B, Miller Larry R, Samano Vicente, Tavares Francis X, Wells-Knecht Kevin J, Wright Lois L, Zhou Hui-Qiang Q

机构信息

Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.

出版信息

Bioorg Med Chem Lett. 2007 Jan 1;17(1):22-7. doi: 10.1016/j.bmcl.2006.10.102. Epub 2006 Nov 17.

DOI:10.1016/j.bmcl.2006.10.102

PMID:17157021

Abstract

Starting from a potent ketone-based inhibitor with poor drug properties, incorporation of P(2)-P(3) elements from a ketoamide-based inhibitor led to the identification of a hybrid series of ketone-based cathepsin K inhibitors with better oral bioavailability than the starting ketone.

摘要

从一种具有不良药物性质的强效酮基抑制剂出发，并入基于酮酰胺的抑制剂中的P(2)-P(3)元素，从而鉴定出一系列基于酮的组织蛋白酶K抑制剂，其口服生物利用度比起始酮更好。