Discovery of selective and nonpeptidic cathepsin S inhibitors

被引：23

作者：

Irie, Osamu ^{[1
]}

Ehara, Takeru ^{[1
]}

Iwasaki, Atsuko ^{[1
]}

Yokokawa, Fumiaki ^{[1
]}

Sakaki, Junichi ^{[1
]}

Hirao, Hajime ^{[1
]}

Kanazawa, Takanori ^{[1
]}

Teno, Naoki ^{[1
]}

Horiuchi, Miyuki ^{[1
]}

Umemura, Ichiro ^{[1
]}

Gunji, Hiroki ^{[1
]}

Masuya, Keiichi ^{[1
]}

Hitomi, Yuko ^{[1
]}

Iwasaki, Genji ^{[1
]}

Nonomura, Kazuhiko ^{[1
]}

Tanabe, Keiko ^{[1
]}

Fukaya, Hiroaki ^{[1
]}

Kosaka, Takatoshi ^{[1
]}

Snell, Christopher R. ^{[2
]}

Hallett, Allan ^{[2
]}

机构：

[1] Novartis Inst BioMed Res, Tsukuba, Ibaraki 3002611, Japan

[2] Novartis Inst BioMed Res, London WC1E 6BS, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 14期

关键词：

cathepsin S inhibitor; pyrrolopyrimidine; nitrile; nonpeptidic; cysteine protease;

D O I：

10.1016/j.bmcl.2008.06.009

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Nonpeptidic, selective, and potent cathepsin S inhibitors were derived from an in-house pyrrolopyrimidine cathepsin K inhibitor by modi. cation of the P2 and P3 moieties. The pyrrolopyrimidine-based inhibitors show nanomolar inhibition of cathepsin S with over 100-fold selectivity against other cysteine proteases, including cathepsin K and L. Some of the inhibitors showed cellular activities in mouse splenocytes as well as oral bioavailabilities in rats. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：3959 / 3962

页数：4

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