Novel 3-Azaindolyl-4-arylmaleimides Exhibiting Potent Antiangiogenic Efficacy, Protein Kinase Inhibition, and Antiproliferative Activity

被引：36

作者：

Ganser, Christopher ^{[1
]}

Lauermann, Eva ^{[1
]}

Maderer, Annett ^{[2
]}

Stauder, Torsten ^{[3
]}

Kramb, Jan-Peter ^{[1
]}

Plutizki, Stanislav ^{[1
]}

Kindler, Thomas ^{[3
]}

Moehler, Markus ^{[2
]}

Dannhardt, Gerd ^{[1
]}

机构：

[1] Johannes Gutenberg Univ Mainz, Dept Pharm, Mainz, Germany

[2] Johannes Gutenberg Univ Mainz, Dept Internal Med 1, D-6500 Mainz, Germany

[3] Johannes Gutenberg Univ Mainz, Dept Internal Med 3, Mainz, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 55卷 / 22期

关键词：

PLUS IRINOTECAN; ANGIOGENESIS; CANCER; DIFFERENTIATION; MECHANISMS; APOPTOSIS; ACYLATION; ERLOTINIB; GROWTH; ASSAY;

D O I：

10.1021/jm301217c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3 beta which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.

引用

页码：9531 / 9540

页数：10

共 40 条

[1]

Aitkenhead M, 1998, DEV DYNAM, V212, P1

[2] Di-tert-butyl dicarbonate and 4-(dimethylamino)pyridine revisited.: Their reactions with amines and alcohols [J].

Basel, Y ;

Hassner, A .

JOURNAL OF ORGANIC CHEMISTRY, 2000, 65 (20) :6368-6380

[3] Tyrosine kinase receptors as attractive targets of cancer therapy [J].

Bennasroune, A ;

Gardin, A ;

Aunis, D ;

Crémel, G ;

Hubert, P .

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2004, 50 (01) :23-38

[4] Mechanisms of angiogenesis and arteriogenesis [J].

Carmeliet, P .

NATURE MEDICINE, 2000, 6 (04) :389-395

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

Carmeliet, P ;

Jain, RK .

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

[6] Excited state tautomerization of azaindole [J].

Cash, MT ;

Schreiner, PR ;

Phillips, RS .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2005, 3 (20) :3701-3706

[7] Molecular mechanisms of blood vessel growth [J].

Conway, EM ;

Collen, D ;

Carmeliet, P .

CARDIOVASCULAR RESEARCH, 2001, 49 (03) :507-521

[8] Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer [J].

Cunningham, D ;

Humblet, Y ;

Siena, S ;

Khayat, D ;

Bleiberg, H ;

Santoro, A ;

Bets, D ;

Mueser, M ;

Harstrick, A ;

Verslype, C ;

Chau, I ;

Van Cutsem, E .

NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (04) :337-345

[9]

Dannhardt G., 2011, EP Patent, Patent No. [08858282.1, 088582821]

[10]

Dannhardt G., 2011, Patent No. [WO 2011/73092 A1, 201173092]

← 1 2 3 4 →