Synthesis of N-alkyl glycine amides as potent inhibitors of leukotriene A4 hydrolase

被引：14

作者：

Ye, Bin ^{[1
]}

Bauman, John ^{[1
]}

Chen, Ming ^{[1
]}

Davey, David ^{[1
]}

Khim, Seock-Kyu ^{[1
]}

King, Beverly ^{[2
,3
]}

Kirkland, Thomas ^{[1
]}

Kochanny, Monica ^{[1
]}

Liang, Amy ^{[1
]}

Lentz, Dao ^{[2
]}

Maya, Karen ^{[1
]}

Mendoza, Lisa ^{[3
]}

Phillips, Gary ^{[1
]}

Selchau, Victor ^{[1
]}

Schlyer, Sabine ^{[1
]}

Tseng, Jih-Lie ^{[2
]}

Wei, Robert G. ^{[1
]}

Ye, Hong ^{[1
]}

Parkinson, John ^{[3
]}

Guilford, William J. ^{[1
]}

机构：

[1] Berlex Biosci, Dept Med Chem, Richmond, CA 94804 USA

[2] Berlex Biosci, Dept Mol Pharmacol, Richmond, CA 94804 USA

[3] Berlex Biosci, Dept Immunol, Richmond, CA 94804 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 14期

关键词：

leukotriene A(4); leukotriene A(4) hydrolase; anti-inflammatory; enzyme inhibitor;

D O I：

10.1016/j.bmcl.2008.06.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and biological evaluation of a series of N-alkyl glycine amide analogs as LTA(4)-h inhibitors and the importance of the introduction of a benzoic acid group to the potency and pharmacokinetic parameters of our analogs are described. The lead compound in the series, 4q, has excellent potency and oral bioavailability. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：3891 / 3894

页数：4

共 17 条

[1] Pharmacology of leukotriene receptor antagonists [J].

Aharony, D .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1998, 157 (06) :S214-S219

[2] Future advances in COPD therapy [J].

Barnes, PJ .

RESPIRATION, 2001, 68 (05) :441-448

[3]

FORDHUTCHINSON AW, 1990, CRIT REV IMMUNOL, V10, P1

[4] 5-LIPOXYGENASE [J].

FORDHUTCHINSON, AW ;

GRESSER, M ;

YOUNG, RN .

ANNUAL REVIEW OF BIOCHEMISTRY, 1994, 63 :383-417

[5] Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues [J].

Goodarzi, K ;

Goodarzi, M ;

Tager, AM ;

Luster, AD ;

von Andrian, UH .

NATURE IMMUNOLOGY, 2003, 4 (10) :965-973

[6] LEUKOTRIENE B-4 PLAYS A CRITICAL ROLE IN THE PROGRESSION OF COLLAGEN-INDUCED ARTHRITIS [J].

GRIFFITHS, RJ ;

PETTIPHER, ER ;

KOCH, K ;

FARRELL, CA ;

BRESLOW, R ;

CONKLYN, MJ ;

SMITH, MA ;

HACKMAN, BC ;

WIMBERLY, DJ ;

MILICI, AJ ;

SCAMPOLI, DN ;

CHENG, JB ;

PILLAR, JS ;

PAZOLES, CJ ;

DOHERTY, NS ;

MELVIN, LS ;

REITER, LA ;

BIGGARS, MS ;

FALKNER, FC ;

MITCHELL, DY ;

LISTON, TE ;

SHOWELL, HJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (02) :517-521

[7] A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction [J].

Helgadottir, A ;

Manolescu, A ;

Helgason, A ;

Thorleifsson, G ;

Thorsteinsdottir, U ;

Gudbjartsson, DF ;

Gretarsdottir, S ;

Magnusson, KP ;

Gudmundsson, G ;

Hicks, A ;

Jonsson, T ;

Grant, SFA ;

Sainz, J ;

O'Brien, SJ ;

Sveinbjornsdottir, S ;

Valdimarsson, EM ;

Matthiasson, SE ;

Levey, AI ;

Abramson, JL ;

Reilly, MP ;

Vaccarino, V ;

Wolfe, ML ;

Gudnason, V ;

Quyyumi, AA ;

Topol, EJ ;

Rader, DJ ;

Thorgeirsson, G ;

Gulcher, JR ;

Hakonarson, H ;

Kong, A ;

Stefansson, K .

NATURE GENETICS, 2006, 38 (01) :68-74

[8] Psoriasis and the arachidonic acid cascade [J].

Ikai, K .

JOURNAL OF DERMATOLOGICAL SCIENCE, 1999, 21 (03) :135-146

[9] Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase [J].

Kirkland, Thomas A. ;

Adler, Marc ;

Bauman, John G. ;

Chen, Ming ;

Haeggstrom, Jesper Z. ;

King, Beverly ;

Kochanny, Monica J. ;

Liang, Amy M. ;

Mendoza, Lisa ;

Phillips, Gary B. ;

Thunnissen, Marjolein ;

Trinh, Lan ;

Whitlow, Marc ;

Ye, Bin ;

Ye, Hong ;

Parkinson, John ;

Guilford, William J. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (09) :4963-4983

[10]

LEWIS RA, 1990, NEW ENGL J MED, V323, P645

← 1 2 →