Nghe Nguyen-Ba

A novel class of 1,3-oxathiolane nucleoside analogues having potent anti-HIV activity

Abstract We have developed a novel class of 1,3-oxathiolane nucleoside analogues which were evaluated for anti-HIV activity in the MT-4 cell line. BCH-371 , the adenine derivative, has been found to exhibit significant anti-HIV activity.

Development of novel nucleoside analogues for use against drug resistant strains of HIV-1

Nucleoside analogue inhibitors of the reverse transcriptase (RT) enzyme of HIV-1 were the first class of compounds to be used in anti-HIV-1 therapy and are a cornerstone in highly active antiretroviral therapy. Despite the number of inhibitors of HIV-1 RT available for clinical use at the present time and the effectiveness of these compounds in combination regimens, long-term exposure of patients to these drugs often results in the development of viral resistance or long-term toxicity. For this reason, efforts to identify new agents with activity against drug-resistant strains of HIV-1 and with a toxicity profile that allows for individual patient tolerance of the drugs are still warranted.

Antiviral optically pure dioxolane purine nucleosides analogues

Abstract Selective deamination of (±) cis 2,6-diaminopurine dioxolane nucleoside produces the (−) guanine analogue having the 2R,4R absolute stereochemistry. The (±) cis-adenine analogue generates the 2R,4R hypoxanthinyl derivative. Asymmetric synthesis of purine dioxolanes have been developed. The (−) adenine and (−) guanine compounds 6 and 7 emerged as potent inhibitors of the HIV-1 replication in vitro .

Structure-Activity Relationship of Pyrimidine Heterosubstituted Nucleoside Analogues

Abstract The structure-activity relationship of sixteen 3-deaza, C-4 substituted pyrimidines and imidazo[1,2-c]pyrimidine bases of 1,3-oxathiolanes and 1,3-dioxolanes revealed good anti-HBV activity in 2.2.15 cells transfected with human hepatitis B virus of the imidazo[1,2-c]pyrimidine nucleosides 21, 25 and 29. Two procedures for the preparation of C-4 substituted analogues are reported based on nucleophilic displacement of a sulfonamide or imidazole by a variety of nitrogen nucleophiles.

Synthesis and antiviral activities of N-9-oxypurine 1,3-dioxolane and 1,3-oxathiolane nucleosides

Two series of 1,3-dioxolanes and 1,3-oxathiolane nucleosides containing N-9-oxypurine were synthesized as potential antiviral agents. These compounds were prepared by reacting the sugar moieties with iodo- or bromotrimethylsilane, followed by treatment with a mixture of sodium hydride and the desired N-hydroxy purine base. The preparation of these N-hydroxybases was also described. No significant antiviral activity was observed against HIV, HBV, HSV-1, HSV-2, or HCMV.

Design and SAR Study of a Novel Class of Nucleotide Analogues as Potent Anti-HCMV Agents

We have developed a novel class of 2-phosphonate 1,3-dioxolane nucleotide analogues, from which the guanine derivative displayed weak anti-HCMV activity. Further SAR studies led to the identification of both cis and trans guanine derivatives of tetrahydrofuran analogues as potent anti-HCMV agents, both in vitro and in vivo, compared to ganciclovir and HPMPC.

Synthesis of N-1-oxypyrimidine 1,3-dioxolane and 1,3-oxathiolane nucleosides

Two series of 1,3-dioxolanes and 1,3-oxathiolane nucleosides containing N-1-oxypyrimidine were synthesized as potential antiviral agents.