Aminoimidazoles as bioisosteres of acylguanidines: novel, potent, selective and orally bioavailable inhibitors of the sodium hydrogen exchanger isoform-1

被引：19

作者：

Ahmad, S ^{[1
]}

Ngu, K ^{[1
]}

Combs, DW ^{[1
]}

Wu, SC ^{[1
]}

Weinstein, DS ^{[1
]}

Liu, W ^{[1
]}

Chen, BC ^{[1
]}

Chandrasena, G ^{[1
]}

Dorso, CR ^{[1
]}

Kirby, M ^{[1
]}

Atwal, KS ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 01期

关键词：

D O I：

10.1016/j.bmcl.2003.09.066

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

dInhibition of the sodium hydrogen exchanger isoform-1 (NHE-1) has been shown to limit damage to the myocardium under ischemic conditions in animals. While most known NHE-1 inhibitors are acylguanidines, this report describes the design and synthesis of a series of heterocyclic inhibitors of NHE-1 including aminoimidazoles with undiminished in vitro activity and oral bioavailability. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：177 / 180

页数：4

共 20 条

[1] Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1 [J].

Ahmad, S ;

Doweyko, LM ;

Dugar, S ;

Grazier, N ;

Ngu, K ;

Wu, SC ;

Yost, KJ ;

Chen, BC ;

Gougoutas, JZ ;

DiMarco, JD ;

Lan, SJ ;

Gavin, BJ ;

Chen, AY ;

Dorso, CR ;

Serafino, R ;

Kirby, M ;

Atwal, KS .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (20) :3302-3310

[2] KINETIC-PROPERTIES OF THE PLASMA-MEMBRANE NA+-H+ EXCHANGER [J].

ARONSON, PS .

ANNUAL REVIEW OF PHYSIOLOGY, 1985, 47 :545-560

[3]

BOOKSTEIN C, 1994, J BIOL CHEM, V269, P29704

[4] TRANSPORT OF H+ AND OF IONIC WEAK ACIDS AND BASES [J].

BORON, WF .

JOURNAL OF MEMBRANE BIOLOGY, 1983, 72 (1-2) :1-16

[5] CLONING, TISSUE DISTRIBUTION, AND FUNCTIONAL-ANALYSIS OF THE HUMAN NA+/H+ EXCHANGER ISOFORM, NHE3 [J].

BRANT, SR ;

YUN, CHC ;

DONOWITZ, M ;

TSE, CM .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1995, 269 (01) :C198-C206

[6]

BRISTOLMYERS SQUIBB, 2001, Patent No. 0127107

[7] A new facile method for the stereoselective synthesis of trans-2-aryl-3,3-dimethylcyclopropane-1-carboxylic acids [J].

Chen, BC ;

Ngu, K ;

Guo, P ;

Liu, W ;

Sundeen, JE ;

Weinstein, DS ;

Atwal, KS ;

Ahmad, S .

TETRAHEDRON LETTERS, 2001, 42 (36) :6227-6229

[8]

DOWNEY JM, 2003, PCT INT APPL WO, V3, P9528

[9] Discovery of zoniporide: A potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility [J].

Guzman-Perez, A ;

Wester, RT ;

Allen, MC ;

Brown, JA ;

Buchholz, AR ;

Cook, ER ;

Day, WW ;

Hamanaka, ES ;

Kennedy, SP ;

Knight, DR ;

Kowalczyk, PJ ;

Marala, RB ;

Mularski, CJ ;

Novomisle, WA ;

Ruggeri, RB ;

Tracey, WR ;

Hill, RJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (06) :803-807

[10] ROLE OF NA+/H+ EXCHANGE IN CARDIAC PHYSIOLOGY AND PATHOPHYSIOLOGY - MEDIATION OF MYOCARDIAL REPERFUSION INJURY BY THE PH PARADOX [J].

KARMAZYN, M ;

MOFFAT, MP .

CARDIOVASCULAR RESEARCH, 1993, 27 (06) :915-924

← 1 2 →