Synthesis and biological evaluation of substituted 6-alkynyl-4-anilinoquinazoline derivatives as potent EGFR inhibitors

被引：42

作者：

Liu, Lee Tai

Yuan, Ta-Tung

Liu, Hung-Huang

Chen, Shyh-Fong

Wu, Ying-Ta

机构：

[1] Dev Ctr Biotechnol, Taipei, Taiwan

[2] Genomics Res Ctr, Taipei, Taiwan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 22期

关键词：

EGFR kinase inhibitor; alkynyl-substituted; 4-anifnoquinazoline;

D O I：

10.1016/j.bmcl.2007.08.061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of C-6 or C-3 ' alkynyl-substituted 4-anilinoquinazoline derivatives was prepared straightforwardly by a Sonogashira reaction of the corresponding bromo-substituted 4-anilinoquinazolines. Bioactive assay of these compounds for in vitro EGFR kinase inhibition demonstrated that the novel 6-hydroxypropynyl-4-anilinoquinazoline 5e was a very potent EGFR kinase inhibitor with an IC50 of 14 nM. (C) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：6373 / 6377

页数：5

相关论文

共 20 条

[1] Studies leading to the identification of ZD1839 (Iressa™):: An orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer [J].

Barker, AJ ;

Gibson, KH ;

Grundy, W ;

Godfrey, AA ;

Barlow, JJ ;

Healy, MP ;

Woodburn, JR ;

Ashton, SE ;

Curry, BJ ;

Scarlett, L ;

Henthorn, L ;

Richards, L .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (14) :1911-1914

[2] Chemical inhibitors of protein kinases [J].

Bridges, AJ .

CHEMICAL REVIEWS, 2001, 101 (08) :2541-2571

[3] Tyrosine kinase inhibitors .8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor [J].

Bridges, AJ ;

Zhou, H ;

Cody, DR ;

Rewcastle, GW ;

McMichael, A ;

Showalter, HDH ;

Fry, DW ;

Kraker, AJ ;

Denny, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (01) :267-276

[4]

Ciardiello F, 2001, CLIN CANCER RES, V7, P2958

[5] Epidermal growth factor inhibition in solid tumours [J].

Ganti, AK ;

Potti, A .

EXPERT OPINION ON BIOLOGICAL THERAPY, 2005, 5 (09) :1165-1174

[6] Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets [J].

Lai, JYQ ;

Langston, S ;

Adams, R ;

Beevers, RE ;

Boyce, R ;

Burckhardt, S ;

Cobb, J ;

Ferguson, Y ;

Figueroa, E ;

Grimster, N ;

Henry, AH ;

Khan, N ;

Jenkins, K ;

Jones, MW ;

Judkins, R ;

Major, J ;

Masood, A ;

Nally, J ;

Payne, H ;

Payne, L ;

Raphy, G ;

Raynham, T ;

Reader, J ;

Reader, Y ;

Reid, A ;

Ruprah, P ;

Shaw, M ;

Sore, H ;

Stirling, M ;

Talbot, A ;

Taylor, J ;

Thompson, S ;

Wada, H ;

Walker, D .

MEDICINAL RESEARCH REVIEWS, 2005, 25 (03) :310-330

[7] Epidermal growth factor receptor: a promising target in solid tumours [J].

Laskin, JJ ;

Sandier, AB .

CANCER TREATMENT REVIEWS, 2004, 30 (01) :1-17

[8] Protein kinase inhibitors as a therapeutic modality [J].

Levitzki, A .

ACCOUNTS OF CHEMICAL RESEARCH, 2003, 36 (06) :462-469

[9] SIGNAL-TRANSDUCTION THERAPY - A NOVEL-APPROACH TO DISEASE MANAGEMENT [J].

LEVITZKI, A .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1994, 226 (01) :1-13

[10] Tyrosine kinase inhibitors in cancer therapy [J].

Madhusudan, S ;

Ganesan, TS .

CLINICAL BIOCHEMISTRY, 2004, 37 (07) :618-635