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Synthesis Of Novel Isoxazole Or Oxime Tethered Uracil-Pyridine Hybrids

Since the discovery of platinum coordination compound cisplatin, the spotlights are directed to rational design of metal compounds that showed various biological activity such anticancer, antimicrobial, antiviral and antidiabetic.1 Pyridine itself is a monodentate ligand having capability to bind metal producing the range of pyridine coordinated complexes of transition metals.2 Uracil nucleosides with various functional groups at the C-5 position have been investigated for their anticancer activity.3 Novel C-5 substituted uracil derivatives bearing isoxazole moiety were synthesized by 1, 3-dipolar cycloaddition of N-1 propargylated uracil derivatives and pyridine-2-aldoxime. On the other hand, oxime linker was introduced by alkylation reaction of C-5 substituted uracil derivatives with corresponding alkylating agent in the presence of base. Linear, aromatic, and cyclopropyl alkynyl moieties were introduced at C- 5 position of uracil using a palladium catalyzed crosscoupling Sonogashira reaction. Synthesized pyridine based uracil ligands will be used for the preparation of metal complexes with the aim to evalute their antiproliferative activity.

isoxazole, oxime, uracil, pyridine, metal complexes

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