N-hydroxyformamide peptidomimetics as TACE/matrix metalloprotease inhibitors:: Oral activity via P1′ isobutyl substitution

被引：19

作者：

Musso, DL ^{[1
]}

Andersen, MW ^{[1
]}

Andrews, RC ^{[1
]}

Austin, R ^{[1
]}

Beaudet, EJ ^{[1
]}

Becherer, JD ^{[1
]}

Bubacz, DG ^{[1
]}

Bickett, DM ^{[1
]}

Chan, JH ^{[1
]}

Conway, JG ^{[1
]}

Cowan, DJ ^{[1
]}

Gaul, MD ^{[1
]}

Glennon, KC ^{[1
]}

Hedeen, KM ^{[1
]}

Lambert, MH ^{[1
]}

Leesnitzer, MA ^{[1
]}

McDougald, DL ^{[1
]}

Mitchell, JL ^{[1
]}

Moss, ML ^{[1
]}

Rabinowitz, MH ^{[1
]}

Rizzolio, MC ^{[1
]}

Schaller, LT ^{[1
]}

Stanford, JB ^{[1
]}

Tippin, TK ^{[1
]}

Warner, JR ^{[1
]}

Whitesell, LG ^{[1
]}

Wiethe, RW ^{[1
]}

机构：

[1] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 16期

关键词：

D O I：

10.1016/S0960-894X(01)00377-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-Hydroxyformamide-class metalloprotease inhibitors were designed and synthesized, which have potent broad-spectrum activity versus matrix metalloproteases and TNF-x converting enzyme (TACE). Compound 13c possesses good oral and intravenous pharmacokinetics in the rat and dog. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：2147 / 2151

页数：5

共 21 条

[1] Inhibition of bovine nasal cartilage degradation by selective matrix metalloproteinase inhibitors [J].

Bottomley, KM ;

Borkakoti, N ;

Bradshaw, D ;

Brown, PA ;

Broadhurst, MJ ;

Budd, JM ;

Elliott, L ;

Eyers, P ;

Hallam, TJ ;

Handa, BK ;

Hill, CH ;

James, M ;

Lahm, HW ;

Lawton, G ;

Merritt, JE ;

Nixon, JS ;

Rothlisberger, U ;

Whittle, A ;

Johnson, WH .

BIOCHEMICAL JOURNAL, 1997, 323 :483-488

[2] Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-alpha inhibitor [J].

Clements, JM ;

Cossins, JA ;

Wells, GMA ;

Corkill, DJ ;

Helfrich, K ;

Wood, LM ;

Pigott, R ;

Stabler, G ;

Ward, GA ;

Gearing, AJH ;

Miller, KM .

JOURNAL OF NEUROIMMUNOLOGY, 1997, 74 (1-2) :85-94

[3]

DOCHERTY AJP, 1990, ANN RHEUM DIS, P469

[4] Anti-TNFα therapy is useful in rheumatoid arthritis and Crohn's disease:: Analysis of the mechanism of action predicts utility in other diseases [J].

Feldman, M ;

Taylor, P ;

Paleolog, E ;

Brennan, FM ;

Maini, RN .

TRANSPLANTATION PROCEEDINGS, 1998, 30 (08) :4126-4127

[5] ABOUT THE STEREOSPECIFIC ALPHA-ALKYLATION OF BETA-HYDROXYESTERS [J].

FRATER, G .

HELVETICA CHIMICA ACTA, 1979, 62 (08) :2825-2828

[6] PROCESSING OF TUMOR-NECROSIS-FACTOR-ALPHA PRECURSOR BY METALLOPROTEINASES [J].

GEARING, AJH ;

BECKETT, P ;

CHRISTODOULOU, M ;

CHURCHILL, M ;

CLEMENTS, J ;

DAVIDSON, AH ;

DRUMMOND, AH ;

GALLOWAY, WA ;

GILBERT, R ;

GORDON, JL ;

LEBER, TM ;

MANGAN, M ;

MILLER, K ;

NAYEE, P ;

OWEN, K ;

PATEL, S ;

THOMAS, W ;

WELLS, G ;

WOOD, LM ;

WOOLLEY, K .

NATURE, 1994, 370 (6490) :555-557

[7] AN IMPROVED PROCEDURE FOR THE SYNTHESIS AND USE OF [RUCL2(BINAP)]2.NET3 - DEPENDENCE OF THE RU(II)-BINAP CATALYZED ASYMMETRIC HYDROGENATION OF BETA-KETO-ESTERS ON TRACE AMOUNTS OF ACID [J].

KING, SA ;

THOMPSON, AS ;

KING, AO ;

VERHOEVEN, TR .

JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (25) :6689-6691

[8]

Leesnitzer MA, 2000, HIGH THROUGHPUT SCREENING FOR NOVEL ANTI-INFLAMMATORIES, P87

[9]

Maini RN, 1998, ARTHRITIS RHEUM, V41, P1552, DOI 10.1002/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO

[10]

2-W

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