Abstract
Nitration of three regioisomers of bromo-fluorobenzaldehyde proceeds regioselectively, notably with H2SO4/HNO3 at 0 °C. The thereby synthesized tetrasubstituted aromatics, endowed with orthogonal substituents, can be elaborated via Pd-catalysed coupling, reduction and reductive amination reactions. As a test-case, these compounds were converted into EGFR inhibitors related to Gefitinib, whose activity was rationalised by docking studies.
MeSH terms
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Amination
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Animals
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CHO Cells
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Catalysis
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Cricetulus
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Drug Discovery / methods
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / metabolism
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Gefitinib
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Humans
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Molecular Docking Simulation
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Molecular Structure
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Palladium / chemistry
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Quinazolines / chemistry
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Small Molecule Libraries / chemical synthesis
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Small Molecule Libraries / chemistry*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Quinazolines
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Small Molecule Libraries
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Palladium
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ErbB Receptors
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Gefitinib