1-Alkyl-5-amino-6-phenylethyluracils （1a, 1b） were synthesized as potential non-nucleoside HIV-1RT inhibitors. A convenient synthetic procedure was developed for the preparation of 1-alkyl-5-amino or 5-aminosubstituted-6-phenylethyluracils, which were synthesized in three or four steps from 6-methyluracil in good yield. The development of a one-pot reaction that simultaneously removed the benzyl protection group and reduced the nitro group greatly improved the yield of the synthesis. Compounds 1a and 1b are analogs of MKC-442, which is an efficient inhibitor of HIV-1 reverse transcriptase, 1a and 1b were tested for their inhibition of HIV-1RT, and moderate activity was found for 1a.
An effective synthesis method for preparing 4,6-disubstituted pyridinones was reported. Ethyl 3-oxo-4-phenylbutyrate was an important intermediate, by which 6-substituted pyridinones could be prepared. The decarboxylation condition was optimized for compound 4. After protected with a methoxy group, the compound was reacted with BnBr to form the target compound 11. The structures were characterized by ^1H NMR, ^13C NMR and HRMS, and its enzyme inhibition activity was also determined.
