4-anilino-3-cyanobenzo[g]quinolines as kinase inhibitors

被引：22

作者：

Zhang, N ^{[1
]}

Wu, BQ

Wissner, A

Powell, DW

Rabindran, SK

Kohler, C

Boschelli, F

机构：

[1] Wyeth Ayerst Res, Chem Sci, Pearl River, NY 10965 USA

[2] Wyeth Ayerst Res, Discovery Oncol, Pearl River, NY 10965 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 03期

关键词：

D O I：

10.1016/S0960-894X(01)00776-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-anilino-3-cyanobenzo[g]quinolines was prepared as potent kinase inhibitors. Compared with their bicyclic 4-anilino- 3 -cyanoquinoline analogues, the tricyclic 4-anilino-3-cyanobenzo[g]quinolines are less active against EGF-R kinase, equally active against MAPK kinase (MEK), and more active against Src kinase. For Src kinase inhibition, the best activity is obtained when both the 7- and 8-positions are substituted with alkoxy groups. Several of these kinase inhibitors show potent growth inhibitory activity in tumor cells. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：423 / 425

页数：3

共 10 条

[1] Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity [J].

Boschelli, DH ;

Ye, F ;

Wang, YD ;

Dutia, M ;

Johnson, SL ;

Wu, BQ ;

Miller, K ;

Powell, DW ;

Yaczko, D ;

Young, M ;

Tischler, M ;

Arndt, K ;

Discafani, C ;

Etienne, C ;

Gibbons, J ;

Grod, J ;

Lucas, J ;

Weber, JM ;

Boschelli, F .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (23) :3965-3977

[2] Synthesis and Src kinase inhibitory activity of a series of 4-phenylamino-3-quinolinecarbonitriles [J].

Boschelli, DH ;

Wang, YD ;

Ye, F ;

Wu, BQ ;

Zhang, N ;

Dutia, M ;

Powell, DW ;

Wissner, A ;

Arndt, K ;

Weber, JM ;

Boschelli, F .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (05) :822-833

[3] MATRIX METALLOPROTEINASE INHIBITORS CONTAINING A (CARBOXYALKYL)AMINO ZINC LIGAND - MODIFICATION OF THE P1 AND P2' RESIDUES [J].

BROWN, FK ;

BROWN, PJ ;

BICKETT, DM ;

CHAMBERS, CL ;

DAVIES, HG ;

DEATON, DN ;

DREWRY, D ;

FOLEY, M ;

MCELROY, AB ;

GREGSON, M ;

MCGEEHAN, GM ;

MYERS, PL ;

NORTON, D ;

SALOVICH, JM ;

SCHOENEN, FJ ;

WARD, P .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (05) :674-688

[4]

MCOMIE JFW, 1973, SYNTHESIS-STUTTGART, P416

[5] Combinatorial chemoprevention of intestinal neoplasia [J].

Torrance, CJ ;

Jackson, PE ;

Montgomery, E ;

Kinzler, KW ;

Vogelstein, B ;

Wissner, A ;

Nunes, M ;

Frost, P ;

Discafani, CM .

NATURE MEDICINE, 2000, 6 (09) :1024-1028

[6] Inhibitors of Src tyrosine kinase: The preparation and structure-activity relationship of 4-anilino-3-cyanoquinolines and 4-anilinoquinazolines [J].

Wang, YD ;

Miller, K ;

Boschelli, DH ;

Ye, F ;

Wu, BQ ;

Floyd, MB ;

Powell, DW ;

Wissner, A ;

Weber, JM ;

Boschelli, F .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (21) :2477-2480

[7] 4-Anilino-6,7-dialkoxyquinolime-3-carbonitrile inhibitors of epidermal growth factor receptor kinase and their bioisosteric relationship to the 4-anilino-6,7-dialkoxyquinazoline inhibitors [J].

Wissner, A ;

Berger, DM ;

Boschelli, DH ;

Floyd, MB ;

Greenberger, LM ;

Gruber, BC ;

Johnson, BD ;

Mamuya, N ;

Nilakantan, R ;

Reich, MF ;

Shen, R ;

Tsou, HR ;

Upeslacis, E ;

Wang, YF ;

Wu, BQ ;

Ye, F ;

Zhang, N .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (17) :3244-3256

[8] MEK (MAPKK) inhibitors. Part 2: Structure-activity relationships of 4-anilino-3-cyano-6,7-dialkoxyquinolines [J].

Zhang, N ;

Wu, BQ ;

Eudy, N ;

Wang, YN ;

Ye, F ;

Powell, D ;

Wissner, A ;

Feldberg, LR ;

Kim, SC ;

Mallon, R ;

Kovacs, ED ;

Toral-Barza, L ;

Kohler, CA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (11) :1407-1410

[9] Synthesis and structure-activity relationships of 3-cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) inhibitors [J].

Zhang, N ;

Wu, BQ ;

Powell, D ;

Wissner, A ;

Floyd, MB ;

Kovacs, ED ;

Toral-Barza, L ;

Kohler, C .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (24) :2825-2828

[10]

ZHANG N, 2000, FRONTIERS BIOTECHNOL, V1, P305

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