title: Synthesis of bicyclic pyrimidine derivatives as ATP analogues.
abstract: A highly efficient and general solid-phase synthesis of bicyclic pyrimidine derivatives that target purine dependent proteins is reported. The synthesis of the key intermediate, 4,6-disubstituted-5-amino-pyrimidine, involved reduction of the corresponding nitro derivatives using 1,1'-dioctyl-viologen in a triphasic milieu. The mild reduction conditions enable the use of any acid labile solid support as well as a wide range of combinatorial substituents, thus enabling the synthesis of large libraries of highly diverse bicyclic pyrimidines. Alternative reduction conditions with tin(II) chloride and structure-reactivity studies are discussed as well.
authors.affiliation: NeoGenesis Drug Discovery, 840 Memorial Drive, Cambridge, Massachusetts 02139, USA. gregm@neogenesis.com
authors.forename: G M
authors.initials: GM
authors.lastname: Makara
authors.forename: W
authors.initials: W
authors.lastname: Ewing
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: E
authors.initials: E
authors.lastname: Wintner
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives*; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D011743:Pyrimidines / Q000138:chemical synthesis*
chemical_list: D006574:Heterocyclic Compounds, 2-Ring; D011743:Pyrimidines; D000255:Adenosine Triphosphate