Novel, potent P2-P3 pyrrolidine derivatives of ketoamide-based cathepsin K inhibitors

被引：20

作者：

Barrett, DG

Catalano, JG ^{[1
]}

Deaton, DN

Hassell, AM

Long, ST

Miller, AB

Miller, LR

Ray, JA

Samano, V

Shewchuk, LM

Wells-Knecht, KJ

Willard, DH

Wright, LL

机构：

[1] GlaxoSmithKline Inc, Dept Med Chem, Res Triangle Pk, NC 27709 USA

[2] GlaxoSmithKline Inc, Discovery Res Computat Analyt & Struct Sci, Res Triangle Pk, NC 27709 USA

[3] GlaxoSmithKline Inc, Dept World Wide Phys Properties, Res Triangle Pk, NC 27709 USA

[4] GlaxoSmithKline Inc, Dept Mol Pharmacol, Res Triangle Pk, NC 27709 USA

[5] GlaxoSmithKline Inc, Dept Res Bioanal & Drug Metab, Res Triangle Pk, NC 27709 USA

[6] GlaxoSmithKline Inc, Dept Gene Express & Prot Purificat, Res Triangle Pk, NC 27709 USA

[7] GlaxoSmithKline Inc, Discovery Res Biol, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 06期

关键词：

cathepsin K; inhibitor; osteoporosis; ketoamide; synthesis;

D O I：

10.1016/j.bmcl.2005.11.101

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from a potent pantolactone ketoamide cathepsin K inhibitor discovered from structural screening, conversion of the lactone scaffold to a pyrrolidine scaffold allowed exploration of the S-3 subsite of cathepsin K. Manipulation of P-3 and P-1' groups afforded potent inhibitors with drug-like properties. (C) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：1735 / 1739

页数：5

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