Pyridinylimidazole inhibitors of Tie2 kinase

被引：36

作者：

Semones, Marcus

Feng, Yanhong

Johnson, Neil

Adams, Jerry L.

Winkler, Jim

Hansbury, Michael

机构：

[1] GlaxoSmithKline Inc, Collegeville, PA 19426 USA

[2] Incyte Pharm, Wilmington, DE USA

[3] Array Biopharma, Boulder, CO USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 17期

关键词：

Tie2; kinase; imidazole; xenograft;

D O I：

10.1016/j.bmcl.2007.06.068

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This communication details the evolution of the screening lead SB-203580, a known CSBP/p38 kinase inhibitor, into a potent and selective Tie2 tyrosine kinase inhibitor. The optimized compound 5 showed efficacy in an in vivo model of angiogenesis and a MOPC-315 plasmacytoma xenograft model. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：4756 / 4760

页数：5

共 11 条

[1] Development of inflammatory angiogenesis by local stimulation of Fas in vivo [J].

Biancone, L ;

DeMartino, A ;

Orlandi, V ;

Conaldi, PG ;

Toniolo, A ;

Camussi, G .

JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (01) :147-152

[2]

Drabkin DL, 1935, J BIOL CHEM, V112, P51

[3] Tie receptors: New modulators of angiogenic and lymphangiogenic responses [J].

Jones, N ;

Iljin, K ;

Dumont, DJ ;

Alitalo, K .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2001, 2 (04) :257-267

[4] Antiangiogenic gene therapy targeting the endothelium-specific receptor tyrosine kinase Tie2 [J].

Lin, PN ;

Buxton, JA ;

Acheson, A ;

Radziejewski, C ;

Maisonpierre, PC ;

Yancopoulos, GD ;

Channon, KM ;

Hale, LP ;

Dewhirst, MW ;

George, SE ;

Peters, KG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8829-8834

[5] Design and synthesis of potent, selective, and orally bioavailable tetrasubstituted imidazole inhibitors of p38 mitogen-activated protein kinase [J].

Liverton, NJ ;

Butcher, JW ;

Claiborne, CF ;

Claremon, DA ;

Libby, BE ;

Nguyen, KT ;

Pitzenberger, SM ;

Selnick, HG ;

Smith, GR ;

Tebben, A ;

Vacca, JP ;

Varga, SL ;

Agarwal, L ;

Dancheck, K ;

Forsyth, AJ ;

Fletcher, DS ;

Frantz, B ;

Hanlon, WA ;

Harper, CF ;

Hofsess, SJ ;

Kostura, M ;

Lin, J ;

Luell, S ;

O'Neill, EA ;

Orevillo, CJ ;

Pang, M ;

Parsons, J ;

Rolando, A ;

Sahly, Y ;

Visco, DM ;

O'Keefe, SJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (12) :2180-2190

[6]

SATO TN, 1998, STRUCTURE, V6, P1117

[7] Structure of the Tie2 RTK domain: Self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail [J].

Shewchuk, LM ;

Hassell, AM ;

Ellis, B ;

Holmes, WD ;

Davis, R ;

Horne, EL ;

Kadwell, SH ;

McKee, DD ;

Moore, JT .

STRUCTURE, 2000, 8 (11) :1105-1113

[8]

Siemeister G, 1999, CANCER RES, V59, P3185

[9]

TSIGKOS S, 2005, EXPERT OPIN INV DRUG, V12, P935

[10] ARYL-SUBSTITUTED 1-HYDROXYIMIDAZOLES AND 1-HYDROXYIMIDAZOLE-N3-OXIDES [J].

VOLKAMER, K ;

ZIMMERMA.HW .

CHEMISCHE BERICHTE-RECUEIL, 1969, 102 (12) :4177-&

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