Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen activator inhibitor-1 (PAI-1)

被引：9

作者：

El-Ayache, Nadine C. ^{[1
]}

Li, Shih-Hon ^{[2
]}

Warnock, Mark ^{[2
]}

Lawrence, Daniel A. ^{[2
]}

Emal, Cory D. ^{[1
]}

机构：

[1] Eastern Michigan Univ, Dept Chem, Ypsilanti, MI 48197 USA

[2] Univ Michigan, Sch Med, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 03期

关键词：

PAI-1; inhibitors; Bis-arylsulfonamide; Aryl sulfonimide; MECHANISM; THROMBOSIS; TYPE-1; ANGIOGENESIS; TIPLAXTININ; DERIVATIVES; MIGRATION; MODEL; MICE;

D O I：

10.1016/j.bmcl.2009.12.051

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inactivators of plasminogen activator inhibitor-1 (PAI-1) have been identified as possible treatments for a range of conditions, including atherosclerosis, venous thrombosis, and obesity. We describe the synthesis and inhibitory activity of a novel series of compounds based on bis-arylsulfonamide and aryl sulfonimide motifs that show potent and specific activity towards PAI-1. Inhibitors containing short linking units between the sulfonyl moieties and a 3,4-dihydroxy aryl substitution pattern showed the most potent inhibitory activity, and retained high specificity for PAI-1 over the structurally-related serpin anti-thrombin III (ATIII). (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：966 / 970

页数：5

共 30 条

[1] PAI-1 - A potential therapeutic target in cancer
Andreasen, Peter A.
[J]. CURRENT DRUG TARGETS, 2007, 8 (09) : 1030 - 1041
[2] Dose-dependent thrombus resolution due to oral plaminogen activator inhibitor (PAI)-I inhibition with tiplaxtinin in a rat stenosis model of venous thrombosis
Baxi, Sanjiv
Crandall, David L.
Meier, Thomas R.
Wrobleski, Shirley
Hawley, Angela
Farris, Diana
Elokdah, Hassan
Sigler, Robert
Schaub, Robert G.
Wakefield, Thomas
Myers, Daniel
[J]. THROMBOSIS AND HAEMOSTASIS, 2008, 99 (04) : 749 - 758
[3] CALE JM, UNPUB
[4] Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent macrophage migration
Cao, Chunzhang
Lawrence, Daniel A.
Li, Yang
Von Arnim, Christine Af
Herz, Joachim
Su, Enming J.
Makarova, Alexandra
Hyman, Bradley T.
Strickland, Dudley K.
Zhang, Li
[J]. EMBO JOURNAL, 2006, 25 (09) : 1860 - 1870
[5] Modulation of adipose tissue development by pharmacological inhibition of PAI-1
Crandall, David L.
Quinet, Elaine M.
El Ayachi, Soulaf
Hreha, Amy L.
Leik, Courtney E.
Savio, Dawn A.
Juhan-Vague, Irene
Alessi, Marie-Christine
[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (10) : 2209 - 2215
[6] Characterization and comparative evaluation of a structurally unique PAI-1 inhibitor exhibiting oral in-vivo efficacy
Crandall, DL
Elokdah, H
Di, L
Hennan, JK
Gorlatova, NV
Lawrence, DA
[J]. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2004, 2 (08) : 1422 - 1428
[7] Biochemical mechanism of action of a diketopiperazine inactivator of plasminogen activator inhibitor-1
Einholm, AP
Pedersen, KE
Wind, T
Kulig, P
Overgaard, MT
Jensen, JK
Bodker, JS
Christensen, A
Charlton, P
Andreasen, PA
[J]. BIOCHEMICAL JOURNAL, 2003, 373 : 723 - 732
[8] Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: Design, synthesis, and preclinical characterization
Elokdah, H
Abou-Gharbia, M
Hennan, JK
McFarlane, G
Mugford, CP
Krishnamurthy, G
Crandall, DL
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (14) : 3491 - 3494
[9] Synthesis and in vitro evaluation of a series of diketopiperazine inhibitors of plasminogen activator inhibitor-1
Folkes, A
Roe, MB
Sohal, S
Golec, J
Faint, R
Brooks, T
Charlton, P
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (19) : 2589 - 2592
[10] Neutralization of plasminogen activator inhibitor I (PAI-1) by the synthetic antagonist PAI-749 via a dual mechanism of action
Gardell, Stephen J.
Krueger, Julie A.
Antrilli, Thomas A.
Elokdah, Hassan
Mayer, Scott
Orcutt, Steven J.
Crandall, David L.
Vlasuk, George P.
[J]. MOLECULAR PHARMACOLOGY, 2007, 72 (04) : 897 - 906

← 1 2 3 →