Abstract
Microwave-assisted synthesis of the pyrazolyl ketone p38 MAPK inhibitor RO3201195 in 7 steps and 15% overall yield, and the comparison of its effect upon the proliferation of Werner Syndrome cells with a library of pyrazolyl ketones, strengthens the evidence that p38 MAPK inhibition plays a critical role in modulating premature cellular senescence in this progeroid syndrome and the reversal of accelerated ageing observed in vitro on treatment with SB203580.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Fibroblasts / drug effects
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Fibroblasts / pathology
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Humans
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Ketones / chemical synthesis
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Ketones / chemistry
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Ketones / pharmacology*
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Microwaves
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry
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Pyrazoles / pharmacology*
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Small Molecule Libraries / chemical synthesis
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Structure-Activity Relationship
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Werner Syndrome / drug therapy
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Werner Syndrome / metabolism
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Werner Syndrome / pathology*
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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5-amino-1-(4-fluorophenyl)-4-(3-(2,3-dihydroxypropoxy)benzoyl)pyrazole
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Ketones
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Protein Kinase Inhibitors
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Pyrazoles
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Small Molecule Libraries
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p38 Mitogen-Activated Protein Kinases