4-amino-2-cyanopyrimidines: Novel scaffold for nonpeptidic cathepsin S inhibitors

被引：18

作者：

Irie, Osamu ^{[1
]}

Yokokawa, Fumiaki ^{[1
]}

Ehara, Takeru ^{[1
]}

Iwasaki, Atsuko ^{[1
]}

Iwaki, Yuki ^{[1
]}

Hitomi, Yuko ^{[1
]}

Konishi, Kazuhide ^{[1
]}

Kishida, Masashi ^{[1
]}

Toyao, Atsushi ^{[1
]}

Masuya, Keiichi ^{[1
]}

Gunji, Hiroki ^{[1
]}

Sakaki, Junichi ^{[1
]}

Iwasaki, Genji ^{[1
]}

Hirao, Hajime ^{[1
]}

Kanazawa, Takanori ^{[1
]}

Tanabe, Keiko ^{[1
]}

Kosaka, Takatoshi ^{[1
]}

Hart, Terance W. ^{[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 / 16期

关键词：

pyrimidine; cathepsin S inhibitors; nitrile; cysteine protease;

D O I：

10.1016/j.bmcl.2008.07.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe here a novel 4-amino-2-cyanopyrimidine scaffold for nonpeptidomimetic cathepsin S selective inhibitors. Some of the synthesized compounds have sub-nanomolar potency and high selectivity toward cathepsin S along with promising pharmacokinetic and physicochemical properties. The key structural features of the inhibitors consist of a combination of a spiro[2.5]oct-6-ylmethylamine P2 group at the 4-position, a small or polar P3 group at the 5-position and/or a polar group at the 6-position of the pyrimidine. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4642 / 4646

页数：5

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