The discovery of N-(1,3-thiazol-2-yl)pyridin-2-amines as potent inhibitors of KDR kinase

被引：34

作者：

Bilodeau, MT

Rodman, LD

McGaughey, GB

Coll, KE

Koester, TJ

Hoffman, W

Hungate, LW

Kendall, RL

McFall, RC

Rickert, KW

Rutledge, RZ

Thomas, KA

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Mol Syst, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Canc Res, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 11期

关键词：

KDR kinase; VEGF;

D O I：

10.1016/j.bmcl.2004.03.052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

An azo-dye lead was modified to a novel N-(1,3-thiazol-2-yl)pyridin-2-amine series of KDR kinase inhibitors through the use of rapid analog libraries. This new class has been found to be potent, selective, and of low molecular weight. Molecular modeling has postulated an interesting conformational preference and binding mode for these compounds in the active site of the enzyme. (C) 2004 Elsevier Ltd. All rights reserved.

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页码：2941 / 2945

页数：5

相关论文

共 18 条

[1] SYNTHESIS AND SECRETION OF VASCULAR-PERMEABILITY FACTOR VASCULAR ENDOTHELIAL GROWTH-FACTOR BY HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS [J].

ADAMIS, AP ;

SHIMA, DT ;

YEO, KT ;

YEO, TK ;

BROWN, LF ;

BERSE, B ;

DAMORE, PA ;

FOLKMAN, J .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 193 (02) :631-638

[2]

BELLESIA F, 1993, GAZZ CHIM ITAL, V123, P629

[3] Kinase insert domain-containing receptor kinase inhibitors as anti-angiogenic agents [J].

Bilodeau, MT ;

Fraley, ME ;

Hartman, GD .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2002, 11 (06) :737-745

[4]

Boyer Stephen J., 2002, Current Topics in Medicinal Chemistry, V2, P973, DOI 10.2174/1568026023393273

[5] Angiogenesis in cancer and other diseases [J].

Carmeliet, P ;

Jain, RK .

NATURE, 2000, 407 (6801) :249-257

[6] The role of VEGF and thrombospondins in skin angiogenesis [J].

Detmar, M .

JOURNAL OF DERMATOLOGICAL SCIENCE, 2000, 24 :S78-S84

[7] THE DEVELOPMENT AND USE OF QUANTUM-MECHANICAL MOLECULAR-MODELS .76. AM1 - A NEW GENERAL-PURPOSE QUANTUM-MECHANICAL MOLECULAR-MODEL [J].

DEWAR, MJS ;

ZOEBISCH, EG ;

HEALY, EF ;

STEWART, JJP .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (13) :3902-3909

[8] ANGIOGENESIS IN CANCER, VASCULAR, RHEUMATOID AND OTHER DISEASE [J].

FOLKMAN, J .

NATURE MEDICINE, 1995, 1 (01) :27-31

[9]

Frisch M.J., 2016, Gaussian 16 Revision C. 01. 2016, V01

[10] The angiogenic pathway 'vascular endothelial growth factor/flk-I (KDR)-receptor' in rheumatoid arthritis and osteoarthritis [J].

Giatromanolaki, A ;

Sivridis, E ;

Atanassou, N ;

Zois, E ;

Thorpe, PE ;

Brekken, RA ;

Gatter, KC ;

Harris, AL ;

Koukourakis, IM ;

Koukourakis, MI .

JOURNAL OF PATHOLOGY, 2001, 194 (01) :101-108