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pubmed:abstractText |
A novel series of 5-propynyl-dUMP derivatives, with a variety of leaving groups on the side-chain, was designed as potential mechanism-based inhibitors of thymidylate synthase (TS), and synthesized from 5-iodo-2'-deoxyuridine by Pd(0)-catalyzed coupling, followed by direct phosphorylation with POCl3. All members of the series inhibited TS competitively with Ki-values of 0.015-18 microM. Analogs with fluorine or imidazole-based leaving groups caused rapid, irreversible inactivation of TS.
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pubmed:affiliation |
Department of Chemistry, University at Buffalo, State University of New York, 457 Cooke Hall, Buffalo, New York 14260, USA.
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