title: Expanding the scope of fused pyrimidines as kinase inhibitor scaffolds: synthesis and modification of pyrido[3,4-d]pyrimidines.
abstract: Fused pyrimidine cores are privileged kinase scaffolds, yet few examples of the 2-amino-pyrido[3,4-d]pyrimidine chemotype have been disclosed in the context of kinase inhibitor programs. Furthermore, no general synthetic route has been reported to access 2-amino-pyrido[3,4-d]pyrimidine derivatives. Here we report a versatile and efficient chemical approach to this class of molecules. Our strategy involves the concise preparation of 8-chloro-2-(methylthio)pyrido[3,4-d]pyrimidine intermediates and their efficient derivatisation to give novel compounds with potential as kinase inhibitors.
authors.affiliation: Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Surrey, SM2 5NG, UK. swen.hoelder@icr.ac.uk.
authors.forename: Paolo
authors.initials: P
authors.lastname: Innocenti
authors.forename: Hannah
authors.initials: H
authors.lastname: Woodward
authors.forename: Lisa
authors.initials: L
authors.lastname: O'Fee
authors.forename: Swen
authors.initials: S
authors.lastname: Hoelder
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001681:Biological Assay; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000255:Adenosine Triphosphate; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2