Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors

被引：54

作者：

Alam, Mahbub ^{[1
]}

Beevers, Rebekah E. ^{[1
]}

Ceska, Tom ^{[1
]}

Davenport, Richard J. ^{[1
]}

Dickson, Karen M. ^{[1
]}

Fortunato, Mara ^{[1
]}

Gowers, Lewis ^{[1
]}

Haughan, Alan F. ^{[1
]}

James, Lynwen A. ^{[1
]}

Jones, Mark W. ^{[1
]}

Kinsella, Natasha ^{[1
]}

Lowe, Christopher ^{[1
]}

Meissner, Johannes W. G. ^{[1
]}

Nicolas, Anne-Lise ^{[1
]}

Perry, Benjamin G. ^{[1
]}

Phillips, David J. ^{[1
]}

Pitt, William R. ^{[1
]}

Platt, Adam ^{[1
]}

Ratcliffe, Andrew J. ^{[1
]}

Sharpe, Andrew ^{[1
]}

Tait, Laura J. ^{[1
]}

机构：

[1] UCB, Cambridge CB21 6GS, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 12期

关键词：

aminopyrimidines; JNK1; JNK2;

D O I：

10.1016/j.bmcl.2007.03.078

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The development of a series of novel aminopyrimidines as inhibitors of c-Jun N-terminal kinases is described. The synthesis, in vitro inhibitory values for JNK1, JNK2 and CDK2, and the in vitro inhibitory value for a c-Jun cellular assay are discussed. (c) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：3463 / 3467

页数：5

相关论文

共 15 条

[1] Therapeutic promise of JNK ATP-noncompetitive inhibitors [J].

Bogoyevitch, MA .

TRENDS IN MOLECULAR MEDICINE, 2005, 11 (05) :232-239

[2]

BOGOYEVITCH MA, 2004, BIOCHIM BIOPHYS ACTA, V89, P1697

[3] Defective T cell differentiation in the absence of Jnk1 [J].

Dong, C ;

Yang, DD ;

Wysk, M ;

Whitmarsh, AJ ;

Davis, RJ ;

Flavell, RA .

SCIENCE, 1998, 282 (5396) :2092-2095

[4] Design and synthesis of the first generation of novel potent, selective, and in vivo active (benzothiazol-2-yl)acetonitrile inhibitors of the c-Jun N-terminal kinase [J].

Gaillard, P ;

Jeanclaude-Etter, I ;

Ardissone, V ;

Arkinstall, S ;

Cambet, Y ;

Camps, M ;

Chabert, C ;

Church, D ;

Cirillo, R ;

Gretener, D ;

Halazy, S ;

Nichols, A ;

Szyndralewiez, C ;

Vitte, PA ;

Gotteland, JP .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (14) :4596-4607

[5] Selective interaction of JNK protein kinase isoforms with transcription factors [J].

Gupta, S ;

Barrett, T ;

Whitmarsh, AJ ;

Cavanagh, J ;

Sluss, HK ;

Derijard, B ;

Davis, RJ .

EMBO JOURNAL, 1996, 15 (11) :2760-2770

[6] Joint damage and inflammation in c-Jun N-terminal kinase 2 knockout mice with passive murine collagen-induced arthritis [J].

Han, ZN ;

Chang, LF ;

Yamanishi, Y ;

Karin, M ;

Firestein, GS .

ARTHRITIS AND RHEUMATISM, 2002, 46 (03) :818-823

[7] Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation [J].

Kyriakis, JM ;

Avruch, J .

PHYSIOLOGICAL REVIEWS, 2001, 81 (02) :807-869

[8] Aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors: Targeting the gatekeeper residue and beyond [J].

Liu, Gang ;

Zhao, Hongyu ;

Liu, Bo ;

Xin, Zhili ;

Liu, Mei ;

Kosogof, Christi ;

Szczepankiewicz, Bruce G. ;

Wang, Sanyi ;

Clampit, Jill E. ;

Gum, Rebecca J. ;

Haasch, Deanna L. ;

Trevillyan, James M. ;

Sham, Hing L. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (22) :5723-5730

[9] Synthesis and SAR of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as novel, selective c-Jun N-terminal kinase inhibitors [J].

Liu, M ;

Xin, ZL ;

Clampit, JE ;

Wang, SY ;

Gum, RJ ;

Haasch, DL ;

Trevillyan, JM ;

Abad-Zapatero, C ;

Fry, EH ;

Sham, HL ;

Liu, G .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (10) :2590-2594

[10] JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development [J].

Sabapathy, K ;

Hu, YL ;

Kallunki, T ;

Schreiber, M ;

David, JP ;

Jochum, W ;

Wagner, EF ;

Karin, M .

CURRENT BIOLOGY, 1999, 9 (03) :116-125