MODIFICATION OF PYRIMIDINE NUCLEOSIDES WITH THE USE OF NICOTINIC-ACID DERIVATIVES

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-nicotynoyl-, 3',5'-di-O-nicotinoyl-, and N-3,3'-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 H-1 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 (CE(50) 10(-5) M).