Regiocontrolled synthesis of 3- and 5-aminopyrazoles, pyrazolo[3,4-d]pyrimidines, pyrazolo[3,4-b]pyridines and pyrazolo[3,4-b]quinolinones as MAPK inhibitors

被引：34
作者：
Bagley, Mark C. [1 ]
Baashen, Mohammed [1 ]
Paddock, Victoria L. [2 ]
Kipling, David [3 ]
Davis, Terence [3 ]
机构：
[1] Univ Sussex, Sch Life Sci, Dept Chem, Brighton BN1 9QJ, E Sussex, England
[2] Cardiff Univ, Sch Chem, Cardiff CF10 3AT, S Glam, Wales
[3] Cardiff Univ, Sch Med, Inst Canc & Genet, Cardiff CF14 4XN, S Glam, Wales
来源：
TETRAHEDRON | 2013年 / 69卷 / 39期
基金：
英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词：
Pyrazoles; Heterocycles; Microwaves; P38; MAPK; JNK1; MICROWAVE-ASSISTED SYNTHESIS; WERNER-SYNDROME CELLS; SELECTIVE P38-ALPHA INHIBITORS; P38; KINASE; SUBSTITUTED PYRAZOLES; PROTEIN; VX-745; AMINOPYRAZOLES; INFLAMMATION; KETONES;
D O I：
10.1016/j.tet.2013.07.055
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Microwave irradiation of a hydrazine and 3-methoxyacrylonitrile, ethoxymethylenemalononitrile or ethyl acetoacetate provides rapid access to 3- or 5-substituted pyrazoles in excellent yield and with total regiocontrol in a process that can be switched from one regioisomer to the other by choice of conditions. Subsequent reaction, either by microwave-assisted hydrolysis and cyclocondensation with formamide, Hantzsch-type three-component reaction with an aldehyde and ketone, or by cyclocondensation with 2-nitrobenzaldehyde, provides the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-b]pyridine or pyrazolo[3,4-b]quinolin-4-one framework, respectively, of inhibitors of mitogen-activated protein kinases. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：8429 / 8438
页数：10
相关论文
共 50 条
[1]   Approaches towards the synthesis of 5-aminopyrazoles [J].
Aggarwal, Ranjana ;
Kumar, Vinod ;
Kumar, Rajiv ;
Singh, Shiv P. .
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, 2011, 7 :179-197
[2]   Versatile three component coupling for the synthesis of pyrazolopyridines and other pyrido fused systems [J].
Almansa, Carmen ;
Virgili, Marina ;
Carceller, Elena ;
Grima-Poveda, Pedro .
HETEROCYCLES, 2008, 75 (07) :1695-1709
[3]  
Almansa R. C., 2004, Int. Patent, Patent No. [W02004076450A1 20040910, 2004076450]
[4]   Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38MAPK inhibitor RO3201195 for study in Werner syndrome cells [J].
Bagley, Mark C. ;
Davis, Terence ;
Dix, Matthew C. ;
Murziani, Paola G. S. ;
Rokicki, Michal J. ;
Kipling, David .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (13) :3745-3748
[5]   Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells [J].
Bagley, Mark C. ;
Davis, Terence ;
Dix, Matthew C. ;
Rokicki, Michal J. ;
Kipling, David .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (18) :5107-5110
[6]   Regioselective microwave-assisted synthesis of substituted pyrazoles from ethynyl ketones [J].
Bagley, Mark C. ;
Lubinu, M. Caterina ;
Mason, Christopher .
SYNLETT, 2007, (05) :704-708
[7]   Microwave-assisted synthesis of N-pyrazole ureas and the p38α inhibitor BIRB 796 for study into accelerated cell ageing [J].
Bagley, Mark C. ;
Davis, Terence ;
Dix, Matthew C. ;
Widdowson, Caroline S. ;
Kipling, David .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2006, 4 (22) :4158-4164
[8]   Use of p38 MAPK Inhibitors for the Treatment of Werner Syndrome [J].
Bagley, Mark C. ;
Davis, Terence ;
Murziani, Paola G. S. ;
Widdowson, Caroline S. ;
Kipling, David .
PHARMACEUTICALS, 2010, 3 (06) :1842-1872
[9]   Gram-scale synthesis of the p38α MAPK-inhibitor VX-745 for preclinical studies into Werner syndrome [J].
Bagley, Mark C. ;
Davis, Terence ;
Dix, Matthew C. ;
Fusillo, Vincenzo ;
Pigeaux, Morgane ;
Rokicki, Michal J. ;
Kipling, David .
FUTURE MEDICINAL CHEMISTRY, 2010, 2 (09) :1417-1427
[10]   Microwave-assisted synthesis of a pyrazolyl ketone library for evaluation as p38 MAPK inhibitors in Werner syndrome cells [J].
Bagley, Mark C. ;
Davis, Terence ;
Dix, Matthew C. ;
Murziani, Paola G. S. ;
Rokicki, Michal J. ;
Kipling, David .
FUTURE MEDICINAL CHEMISTRY, 2010, 2 (02) :203-213
12345