Modification of pyrimidine nucleosides using nicotinic acid derivatives
Makutova, S.V.; Plikhtiak, I.L.; Iartseva, I.V.; Ivanova, T.P.; Mel'nik, S.I.
Bioorganicheskaia Khimiia 21(4): 289-295
1995
ISSN/ISBN: 0132-3423 PMID: 7786320 Document Number: 447869
Interaction of nicotinoyl chloride in situ with 2'-deoxyuridine, its 3'-O-acetyl-, or 5'-O-trityl derivatives led to 3'-O-nicotinoyl-, 5'-O-nicotinoyl-, 3',5'-di-O-nicotinoyl-, and N3,3'-di-O-nicotinoyl-2'-deoxyuridine. Similarly, 5'-O-nicotinoyl-6-azauridine resulted from the reaction of 2',3'-O-ethoxymethylidene-6-azauridine followed by the deprotection. Reaction of 5'-amino-5'-deoxy-2',3'-O-ethoxymethylidene-6-azauridine with nicotinic acid in the presence of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline followed by the cleavage of the 2',3'-O-protecting group gave 5'-deoxy-5'-nicotinamido-6-azauridine. The same compound was obtained from 5'-amino-5'-deoxy-6-azauridine and N-succinimidyl nicotinate. Structures of the compounds obtained were corroborated by 1H NMR spectra. It is shown that 3',5'-di-O-nicotinoyl-2'- deoxyuridine and 5'-deoxy-5'-O-nicotinamido-6-azauridine are cytotoxic toward CaOv cells in vitro (CE50 10(-5) M).