title: Elaboration of tetra-orthogonally-substituted aromatic scaffolds towards novel EGFR-kinase inhibitors.
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.
authors.affiliation: Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, BN1 9QJ, UK. j.spencer@sussex.ac.uk.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Close
authors.forename: Rhiannon N
authors.initials: RN
authors.lastname: Jones
authors.forename: Cory A
authors.initials: CA
authors.lastname: Ocasio
authors.forename: Paul
authors.initials: P
authors.lastname: Kemmitt
authors.forename: S Mark
authors.initials: SM
authors.lastname: Roe
authors.forename: John
authors.initials: J
authors.lastname: Spencer
mesh_terms: D000586:Amination; D000818:Animals; D016466:CHO Cells; D002384:Catalysis; D003412:Cricetulus; D055808:Drug Discovery / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D011799:Quinazolines / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D054852:Small Molecule Libraries; D010165:Palladium; D066246:ErbB Receptors; D000077156:Gefitinib