Microwave-assisted synthesis of N-pyrazole ureas and the p38alpha inhibitor BIRB 796 for study into accelerated cell ageing.
Microwave irradiation of substituted hydrazines and beta-ketoesters gives 5-aminopyrazoles in excellent yield, which can be transformed to the corresponding N-carbonyl derivatives by treatment with an isocyanate or chloroformate. Derivatization of 4-nitronaphth-1-ol using predominantly microwave heating methods and reaction with an N-pyrazole carbamate provides a rapid route to the N-pyrazole urea BIRB 796 in high purity, as a potent and selective inhibitor of p38alpha mitogen-activated protein kinase for the study of accelerated ageing in Werner syndrome cells.
Bagley
Mark C
MC
School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff, UK. Bagleymc@cardiff.ac.uk
Davis
Terence
T
Dix
Matthew C
MC
Widdowson
Caroline S
CS
Kipling
David
D
D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology / Q000528:radiation effects; D006801:Humans; D008872:Microwaves; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000494:pharmacology / Q000528:radiation effects; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000528:radiation effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014898:Werner Syndrome / Q000201:enzymology; D010671:Phenylurea Compounds
D004791:Enzyme Inhibitors; D048308:Mitogen-Activated Protein Kinase 14; D009281:Naphthalenes; D011720:Pyrazoles; C452139:doramapimod; D010671:Phenylurea Compounds