Dual function inhibitors of relevance to chronic obstructive pulmonary disease

被引：6

作者：

Dou, Dengfeng ^{[1
]}

He, Guijia ^{[1
]}

Alliston, Kevin R. ^{[1
]}

Groutas, William C. ^{[1
]}

机构：

[1] Wichita State Univ, Dept Chem, Wichita, KS 67260 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 10期

基金：

美国国家卫生研究院;

关键词：

Elastase; Caspase-1; ICE; Inhibitor; Dual function; MECHANISM-BASED INHIBITORS; SERINE PROTEASES; PATHOGENESIS; EMPHYSEMA; APOPTOSIS; SCAFFOLD; COPD; PROTEINASES; DESTRUCTION; ELASTASE;

D O I：

10.1016/j.bmcl.2010.12.033

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The general strategy and rationale underlying the design of COPD therapeutics that possess protease inhibitory activity and are also capable of releasing a species that attenuates inflammation by inhibiting caspase-1, are described. The synthesis and in vitro biochemical evaluation of a dual function molecule that sequentially inhibits HNE and caspase-1 in a time-dependent manner is reported. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：3177 / 3180

页数：4

共 33 条

[1]

Abboud RT, 2008, INT J TUBERC LUNG D, V12, P361

[2]

[Anonymous], 2008, SYBYL 8 0

[3] Alveolar wall apoptosis causes lung destruction and emphysematous changes [J].

Aoshiba, K ;

Yokohori, N ;

Nagai, A .

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2003, 28 (05) :555-562

[4] Emerging Pharmacotherapies for COPD [J].

Barnes, Peter J. .

CHEST, 2008, 134 (06) :1278-1286

[5] X-RAY CRYSTAL-STRUCTURE OF THE COMPLEX OF HUMAN-LEUKOCYTE ELASTASE (PMN ELASTASE) AND THE 3RD DOMAIN OF THE TURKEY OVOMUCOID INHIBITOR [J].

BODE, W ;

WEI, AZ ;

HUBER, R ;

MEYER, E ;

TRAVIS, J ;

NEUMANN, S .

EMBO JOURNAL, 1986, 5 (10) :2453-2458

[6]

Chua Felix, 2006, Proc Am Thorac Soc, V3, P424, DOI 10.1513/pats.200603-078AW

[7] The Role of Interleukin-1β in Murine Cigarette Smoke-induced Emphysema and Small Airway Remodeling [J].

Churg, Andrew ;

Zhou, Steven ;

Wang, Xiaoshan ;

Wang, Rona ;

Wright, Joanne L. .

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2009, 40 (04) :482-490

[8] VALIDATION OF THE GENERAL-PURPOSE TRIPOS 5.2 FORCE-FIELD [J].

CLARK, M ;

CRAMER, RD ;

VANOPDENBOSCH, N .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1989, 10 (08) :982-1012

[9] Clinical research in chronic obstructive pulmonary disease - Needs and opportunities [J].

Croxton, TL ;

Weinmann, GG ;

Senior, RM ;

Wise, RA ;

Crapo, JD ;

Buist, AS .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 167 (08) :1142-1149

[10] Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema [J].

Demedts, Ingel K. ;

Demoor, Tine ;

Bracke, Ken R. ;

Joos, Guy F. ;

Brusselle, Guy G. .

RESPIRATORY RESEARCH, 2006, 7 (1)

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