Design and synthesis of 3,7-diarylimidazopyridines as inhibitors of the VEGF-receptor KDR

被引：45

作者：

Wu, ZC

Fraley, ME

Bilodeau, MT

Kaufman, ML

Tasber, ES

Balitza, AE

Hartman, GD

Coll, KE

Rickert, K

Shipman, J

Shi, B

Sepp-Lorenzino, L

Thomas, KA

机构：

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 04期

关键词：

D O I：

10.1016/j.bmcl.2003.12.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

3,7-Diaryl substituted imidazopyridines were designed and developed as a new class of KDR kinase inhibitors. A variety of imidazopyridines were synthesized and potent inhibitors of KDR kinase activity were identified with good aqueous solubility. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：909 / 912

页数：4

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] Design and synthesis of 1,5-diarylbenzimidazoles as inhibitors of the VEGF-receptor KDR [J].

Bilodeau, MT ;

Cunningham, AM ;

Koester, TJ ;

Ciecko, PA ;

Coll, KE ;

Huckle, WR ;

Hungate, RW ;

Kendall, RL ;

McFall, RC ;

Mao, XZ ;

Rutledge, RZ ;

Thomas, KA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (15) :2485-2488

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

FOLKMAN, J .

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

[8] Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors:: Improvements in physical properties enhance cellular activity and pharmacokinetics [J].

Fraley, ME ;

Rubino, RS ;

Hoffman, WF ;

Hambaugh, SR ;

Arrington, KL ;

Hungate, RW ;

Bilodeau, MT ;

Tebben, AJ ;

Rutledge, RZ ;

Kendall, RL ;

McFall, RC ;

Huckle, WR ;

Coll, KE ;

Thomas, KA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (24) :3537-3541

[9] Synthesis and initial SAR studies of 3,6-disubstituted pyrazolol[1,5-a]pyrimidines:: A new class of KDR kinase inhibitors [J].

Fraley, ME ;

Hoffman, WF ;

Rubino, RS ;

Hungate, RW ;

Tebben, AJ ;

Rutledge, RZ ;

McFall, RC ;

Huckle, WR ;

Kendall, RL ;

Coll, KE ;

Thomas, KA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (19) :2767-2770

[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