Potent and selective cathepsin K inhibitors

被引：13

作者：

Shinozuka, Tsuyoshi

Shimada, Kousei

Matsui, Satoshi

Yamane, Takahiro

Ama, Mayumi

Fukuda, Takeshi

Taki, Motohiko

Takeda, Yuko

Otsuka, Eri

Yamato, Michiko

Mochizuki, Shin-ichi

Ohhata, Keiko

Naito, Satoru

机构：

[1] Sankyo Co Ltd, Med Chem Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

[2] Sankyo Co Ltd, Lead Discovery Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

[3] Sankyo Co Ltd, Biol Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 20期

关键词：

cathepsin K; inhibitor; SAR study; OVX rat assay;

D O I：

10.1016/j.bmc.2006.06.032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A novel series of cathepsin K inhibitors derived from Novartis compound I is described. Optimization of the P1, P3, and P1' units led to the identification of 4-aminophenoxyacetic acid 24b with an IC50 value of 4.8 nM, which possessed an excellent selectivity over other human cathepsins and good pharmacokinetic (PK) properties. Oral administration of compound 24b to ovariectomized (OVX) rats showed a trend toward an improvement of bone mineral density (BMD) in the femur bone. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：6789 / 6806

页数：18

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