1041364-75-3Relevant academic research and scientific papers
Pyrimidine acyclic nucleotide analogues with aromatic substituents in C-5 position
Krecmerova, Marcela,Holy, Antonin,Masojidkova, Milena
, p. 927 - 951 (2008/09/20)
NH2-protected 5-phenylcytoslne and its derivatives 2a-2d were treated with (2S)-2-[(trityloxy)methyl]oxirane (3) followed by etheriflcation with diisopropyl [(tosyloxy)methyl]phosphonate (5) in the presence of sodium hydride. The intermediary phosphonate esters 6 were debenzoylated and subsequently transformed to free phosphonic acids, i.e. (S)-1-[3-hydroxy-2- (phosphonomethoxy)propyl]-5-phenylcytosine (5-phenyl-HPMPC) derivatives (8a-8d) by the action of bromotrimethylsilane and subsequent hydrolysis. Deamination of these compounds with 3-methylbutyl nitrite afforded corresponding (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-phenyluracil (5-phenyl-HPMPU) derivatives (9a-9d). R-Enantiomers 14 and 15 were prepared analogously starting from (2R)-2-[(trityloxy)methyl]oxirane. 5-Benzyl-, 5-[(1-naphthyl)methyl]- and 5-[(2-naphthyl)methyl]HPMPU (24a-24c) and -HPMPC (25a-25c) were synthesized from appropriate 5-arylmethyl-4-methoxypyrimidin-2(lH)-ones similarly as described for 5-phenyl derivatives. Antiviral activity was found for (S)-l-[3-hydroxy-2- (phosphonomethoxy)propyl]-5-phenyluracil (9a) (HSV-1 and HSV-2) and (R)-1-[3-hydroxy2-(phosphonomethoxy)propyl]-5-phenylcytosine (14) (cytomegalovirus and varicella-zoster virus), both tested in cell cultures. Some of the 5-phenyluracil derivatives possessed inhibitory activity against thymidine Phosphorylase from SD-lymphoma.
