Synthesis and structure-activity relationship of aminopyrimidine IKK2 inhibitors

被引：22

作者：

Bingham, Alistair H. ^{[1
]}

Davenport, Richard J. ^{[1
]}

Fosbeary, Richard ^{[1
]}

Gowers, Lewis ^{[1
]}

Knight, Roland L. ^{[1
]}

Lowe, Christopher ^{[1
]}

Owen, David A. ^{[1
]}

Parry, David M. ^{[1
]}

Pitt, Will R. ^{[1
]}

机构：

[1] UCB, Cambridge CB21 6GS, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 12期

关键词：

IKK2; aminopyrimidine; inflammation; kinase;

D O I：

10.1016/j.bmcl.2008.04.062

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and structure-activity relationship of a novel series of aminopyrimidines are exemplified. Results of key compounds from within this series in the E-selectin reporter cell assay are also reported. (C) 2008 Elsevier Ltd. All rights reserved.

引用

收藏

页码：3622 / 3627

页数：6

相关论文

共 16 条

[1] NF-kappa B: Ten years after [J].

Baeuerle, PA ;

Baltimore, D .

CELL, 1996, 87 (01) :13-20

[2] The NF-kappa B and I kappa B proteins: New discoveries and insights [J].

Baldwin, AS .

ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :649-683

[3]

BHAGWAT SS, 2001, ACR ANN SCI M SAN FR

[4] A novel series of potent and selective IKK2 inhibitors [J].

Bingham, AH ;

Davenport, RJ ;

Gowers, L ;

Knight, RL ;

Lowe, C ;

Owen, DA ;

Parry, DM ;

Pitt, WR .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (02) :409-412

[5] A cytokine-responsive I kappa B kinase that activates the transcription factor NF-kappa B [J].

DiDonato, JA ;

Hayakawa, M ;

Rothwarf, DM ;

Zandi, E ;

Karin, M .

NATURE, 1997, 388 (6642) :548-554

[6] Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties [J].

Ertl, P ;

Rohde, B ;

Selzer, P .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (20) :3714-3717

[7]

GRIFFITHS RJ, 1997, RHEUMATOID ARTHRITIS, V1, P473

[8] Abnormal morphogenesis but intact IKK activation in mice lacking the IKKα subunit of IκB kinase [J].

Hu, YL ;

Baud, V ;

Delhase, M ;

Zhang, PL ;

Deerinck, T ;

Ellisman, M ;

Johnson, R ;

Karin, M .

SCIENCE, 1999, 284 (5412) :316-320

[9] Severe liver degeneration in mice lacking the IκB kinase 2 gene [J].

Li, QT ;

Van Antwerp, D ;

Mercurio, F ;

Lee, KF ;

Verma, IM .

SCIENCE, 1999, 284 (5412) :321-325

[10] IKK1-deficient mice exhibit abnormal development of skin and skeleton [J].

Li, QT ;

Lu, QX ;

Hwang, JY ;

Büscher, D ;

Lee, KF ;

Izpisua-Belmonte, JC ;

Verma, IM .

GENES & DEVELOPMENT, 1999, 13 (10) :1322-1328