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
收藏
页码：6789 / 6806
页数：18
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