Antiviral activity of 3-(3,5-dimethylbenzyl)uracil derivatives against HIV-1 and HCMV.

Antiviral activity of 1,3-disubstituted uracil derivatives was evaluated against HIV-1 and HCMV. It appears that the nitrogen of the 1-cyanomethyl group is important for anti-HIV-1 activity, suggesting interaction with the amino acid residues of HIV-1 reverse transcriptase. 1-Arylmethyl derivatives also exhibited good anti-HIV-1 activity; and that of the 2- and 4-picolyl derivatives was particularly excellent.

Synthesis and antiviral activity of 1-substituted 3-(3,5-dimethylbenzyl)uracil against HIV-1.

1,3-disubstituted uracils were obtained from uracil by the stepwise alkylation at N-1 and N-3 position with alkyl halide/alkali or alcohol under Mitsunobu conditions. The antiviral activity against HIV-1 of these compounds was examined to find that 1-cyanomethyl-3-(3,5-dimethylbenzyl)uracil and 1-phenyl-3-(3,5-dimethyl-benzyl)uracil showed powerful inhibition.

Synthesis and anti-HIV-1 and anti-HCMV activity of 1-substituted 3-(3,5-dimethylbenzyl)uracil derivatives.

3-(3,5-Dimethylbenzyl)uracil (3) was treated with alkyl halides in the presence of alkali to give 1-substituted congeners. Condensation of 3 with alcohols using the Mitsunobu reaction was also employed as an alternative method. The anti-HIV-1 activity of 1-substituted analogues of 3-(3,5-dimethylbenzyl)uracil was evaluated according to previously established procedures.

Synthesis and antiviral activity of 1,3-disubstituted uracils against HIV-1 and HCMV.

The development of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) is an efficient strategy for finding new therapeutic agents against human immunodeficiency virus (HIV). A large number of 6-substituted uracil derivatives have been prepared in order to explore new NNRTIs. However, there are few approaches to anti-HIV agents from 1,3-disubstituted uracil derivatives.

Introduction of a benzyl group onto the 2'-OH of 6-chloropurine 3'-O-benzoylriboside.

A new method to introduce a benzyl group onto the 2'-OH of purine ribonucleoside is described. Thus, 6-chloropurine 3'-O-benzoylriboside and its 5'-O-trityl congener were condensed with benzyl alcohol using the Mitsunobu reaction to give the 2'-O-benzyl derivative. The yields were varied from 4.

Synthesis and hypnotic-sedative activities of N-substituted uracil on mice.

N3-Phenacyl-N1-substituted uracils 3a-q were synthesized by introduction of substituents at the N1-position of N3-phenacyluracil 2, and their hypnotic and sedative activities were evaluated. Pharmacological activities of these N3-phenacyl-N1-substituted uracils were examined using hypnotic activity and synergistic effects with pentobarbital or diazepam for the hypnotic and sedative activities.

A new method for the synthesis of 2'-O-benzyladenosine using Mitsunobu reaction.

A new method to introduce a benzyl group onto the 2'-OH of purine ribonucleoside is described. Thus, 6-chloropurine 3'-O-benzoylriboside and its 5'-O-trityl congener were condensed with benzyl alcohol using the Mitsunobu reaction to give the 2'-O-benzyl derivative. The yields were varied from 4.

Synthesis of 2'-deoxy-2'-fluoroguanyl-(3',5')-guanosine.

The protected analogue of 2-amnio-6-chloropurine arabinoside (3b) was subjected to reaction with diethylaminosulfur trifluoride (DAST) and subsequently treated with NaOAc in Ac2O/AcOH to give N2, O3', O5'-triacetyl-2'-deoxy-2'-fluoroguanosine (5a). After deacetylation of the sugar moiety and protection of 5'-OH by a 4,4'-dimethoxytrityl group, this nucleoside component was converted to 2'-deoxy-2'-fluoroguanyl-(3',5')-guanosine (6c, GfpG).