Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38MAPK inhibitor RO3201195 for study in Werner syndrome cells

被引：28

作者：

Bagley, Mark C. ^{[1
]}

Davis, Terence ^{[2
]}

Dix, Matthew C. ^{[1
]}

Murziani, Paola G. S. ^{[1
]}

Rokicki, Michal J. ^{[2
]}

Kipling, David ^{[2
]}

机构：

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

[2] Cardiff Univ, Sch Chem, Dept Pathol, Cardiff CF14 4XN, S Glam, Wales

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 13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; RO3201195; microwaves; heterocycles;

D O I：

10.1016/j.bmcl.2008.05.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

5-Aminopyrazol-4-yl ketones are prepared rapidly and efficiently using microwave dielectric heating from beta-ketonitriles by treatment with N, N'-diphenylformamidine followed by heterocyclocondensation by irradiation with a hydrazine. The inhibitory activity of RO3201195 prepared by this methodology was confirmed in hTERT-immortalized HCA2 and WS dermal fibroblasts at 200 nM concentration, both by ELISA and immunoblot assay, and displays excellent kinase selectivity for p38 alpha MAPK over the related stress-activated kinase JNK. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：3745 / 3748

页数：4

共 20 条

[1] Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells
Bagley, Mark C.
Davis, Terence
Dix, Matthew C.
Rokicki, Michal J.
Kipling, David
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (18) : 5107 - 5110
[2] Regioselective microwave-assisted synthesis of substituted pyrazoles from ethynyl ketones
Bagley, Mark C.
Lubinu, M. Caterina
Mason, Christopher
[J]. SYNLETT, 2007, (05) : 704 - 708
[3] 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
[4] Replicative senescence: An old lives' tale?
Campisi, J
[J]. CELL, 1996, 84 (04) : 497 - 500
[5] 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
[6] Synthesis and in vivo activity of MK2 and MK2 substrate-selective p38αMAPK inhibitors in Werner syndrome cells
Davis, Terence
Bagley, Mark C.
Dix, Matthew C.
Murziani, Paola G. S.
Rokicki, Michal J.
Widdowson, Caroline S.
Zayed, Jameel M.
Bachler, Marcus A.
Kipling, David
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (24) : 6832 - 6835
[7] 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
[8] Prevention of Accelerated Cell Aging in the Werner Syndrome
Davis, Terence
Haughton, Michele F.
Jones, Christopher J.
Kipling, David
[J]. UNDERSTANDING AND MODULATING AGING, 2006, 1067 : 243 - 247
[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] The preparation of benzoylacetic ester and some of its homologs
Dorsch, JB
McElvain, SM
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1932, 54 : 2960 - 2964

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