Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells

被引：46

作者：

Bagley, Mark C.

Davis, Terence

Dix, Matthew C.

Rokicki, Michal J.

Kipling, David

机构：

[1] Univ Cardiff Wales, Sch Chem, Cardiff CF10 3AT, Wales

[2] Univ Cardiff Wales, Sch Med, Dept Pathol, Cardiff CF14 4XN, Wales

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 18期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

p38; MAPK; Werner syndrome; VX-745; microwaves; heterocycles; ullmann coupling; palladium;

D O I：

10.1016/j.bmcl.2007.07.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The p38 mitogen-activated protein kinase inhibitor VX-745 is prepared rapidly and efficiently in a four-step sequence using a combination of conductive heating and microwave-niediated steps. Its inhibitory activity was confirmed in hTERT immortalized HCA2 and WS dermal fibroblasts at 0.5-1.0 mu M concentration by ELISA and immunoblot assay, and displays excellent kinase selectivity over the related stress-activated kinase JNK. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：5107 / 5110

页数：4

共 31 条

[1] [Anonymous], 2000, CHEM ABSTR, V133
[2] Microwave-assisted synthesis of N-pyrazole ureas and the p38α inhibitor BIRB 796 for study into accelerated cell ageing
Bagley, Mark C.
Davis, Terence
Dix, Matthew C.
Widdowson, Caroline S.
Kipling, David
[J]. ORGANIC & BIOMOLECULAR CHEMISTRY, 2006, 4 (22) : 4158 - 4164
[3] Normal telomere erosion rates at the single cell level in Werner syndrome fibroblast cells
Baird, DM
Davis, T
Rowson, J
Jones, CJ
Kipling, D
[J]. HUMAN MOLECULAR GENETICS, 2004, 13 (14) : 1515 - 1524
[4] Bemis G. W., 2000, US, Patent No. [6147080, 6147080 A1]
[5] Bemis GW., 1998, patent, Patent No. [WO9827098, 9827098]
[6] Replicative senescence: An old lives' tale?
Campisi, J
[J]. CELL, 1996, 84 (04) : 497 - 500
[7] Prevention of accelerated cell aging in Werner syndrome using a p38 mitogen-activated protein kinase inhibitor
Davis, T
Baird, DM
Haughton, MF
Jones, CJ
Kipling, D
[J]. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2005, 60 (11): : 1386 - 1393
[8] The role of cellular senescence in Werner syndrome - Toward therapeutic intervention in human premature aging
Davis, Terence
Wyllie, Fiona S.
Rokicki, Michal J.
Bagley, Mark C.
Kipling, David
[J]. BIOGERONTOLOGY: MECHANISMS AND INTERVENTIONS, 2007, 1100 : 455 - 469
[9] Werner syndrome as an example of inflamm-aging: Possible therapeutic opportunities for a progeroid syndrome?
Davis, Terence
Kipling, David
[J]. REJUVENATION RESEARCH, 2006, 9 (03) : 402 - 407
[10] P38 Inhibitors: beyond pyridinylimidazoles
Dominguez, C
Tamayo, N
Zhang, DW
[J]. EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (07) : 801 - 816

← 1 2 3 4 →