Further studies on ethenyl and ethynyl-4-phenylamino-3-quinolinecarbonitriles: identification of a subnanomolar Src kinase inhibitor

被引：18

作者：

Carolina, A

Sosa, B

Boschelli, DH

Wu, BQ

Wang, Y

Golas, JM

机构：

[1] Roche Carolina Inc, Pharmaceut Proc Dev, Florence, SC 29506 USA

[2] Wyeth Ayerst Res, Chem & Screening Sci, Pearl River, NY 10965 USA

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 06期

关键词：

Src; kinase; 3-quinolinecarbonitriles;

D O I：

10.1016/j.bmcl.2005.01.004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several new ethynyl- and ethenyl-4-phenylamino-3-quinolinecarbonitriles were synthesized and tested for Src inhibition. Derivatives bearing an ethenyl or ethynyl substituent at C-6 showed decreased Src inhibitory activity. Incorporation of an ethenylpyridine N-oxide group at C-7 provided 20b, a 0.6 nM inhibitor of Src enzymatic activity with excellent cellular potency. (c) 2005 Published by Elsevier Ltd.

引用

收藏

页码：1743 / 1747

页数：5

相关论文

共 14 条

[1] Substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles as Src kinase inhibitors [J].

Berger, D ;

Dutia, M ;

Powell, D ;

Wissner, A ;

DeMorin, F ;

Raifeld, Y ;

Weber, J ;

Boschelli, F .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (20) :2989-2992

[2] 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

[3] 7-alkoxy-4-phenylamino-3-quinolinecarbonitriles as dual inhibitors of Src and Abl kinases [J].

Boschelli, DH ;

Wang, YND ;

Johnson, S ;

Wu, BQ ;

Ye, F ;

Sosa, ACB ;

Golas, JM ;

Boschelli, F .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (07) :1599-1601

[4] Investigation of the effect of varying the 4-anilino and 7-alkoxy groups of 3-quinolinecarbonitriles on the inhibition of Src kinase activity [J].

Boschelli, DH ;

Fe, Y ;

Wu, BQ ;

Wang, YD ;

Sosa, ACB ;

Yaczko, D ;

Powell, D ;

Golas, JM ;

Lucas, J ;

Boschelli, F .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (21) :3797-3800

[5] Inhibition of Src kinase activity by 4-anilino-7-thienyl-3-quinolinecarbonitriles [J].

Boschelli, DH ;

Wang, DY ;

Ye, F ;

Yamashita, A ;

Zhang, N ;

Powell, D ;

Weber, J ;

Boschelli, F .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (15) :2011-2014

[6] 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

[7] Role of Src in signal transduction pathways [J].

Courtneidge, SA .

BIOCHEMICAL SOCIETY TRANSACTIONS, 2002, 30 :11-17

[8] Src in cancer: deregulation and consequences for cell behaviour [J].

Frame, MC .

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2002, 1602 (02) :114-130

[9]

Golas JM, 2003, CANCER RES, V63, P375

[10] Targeting protein kinases for bone disease: Discovery and development of Src inhibitors [J].

Metcalf, CA ;

van Schravendijk, MR ;

Dalgarno, DC ;

Sawyer, TK .

CURRENT PHARMACEUTICAL DESIGN, 2002, 8 (23) :2049-2075