Synthesis of bicyclic pyrimidine derivatives as ATP analogues |
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Authors: | Makara G M Ewing W Ma Y Wintner E |
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Affiliation: | NeoGenesis Drug Discovery, 840 Memorial Drive, Cambridge, Massachusetts 02139, USA. gregm@neogenesis.com |
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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. |
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