Synthesis And Anti-HIV Activity Of Novel1,3-thiazolindin-4-one Derivatives

4-Thiazolidinone is a class of broad pharmacodynamical group, and its derivatives possessdiverse biological activities of bactericidal, antivirus, anti-inflammatory, anti-tumor etc. Aseries of novel thiazolidin-4-one derivatives possessing hydrophilic group and alkyl amide atN-3were synthesized and evaluated for their HIV-1reverse transcriptases inhibitoryactivities.1. A series of new1,3-thiazolidin-4-one compounds were synthesized by the three-component one-pot cyclocondensation of glyoxylic acid ethyl ester, aromatic amines andmercaptoacetic acid using a microwave-assisted method, further reduction by NaBH4orhydrolysis to obtain a series of novel thiazolidin-4-one derivatives possessing carboxyl andhydroxyl groups at C-2or N-3, and evaluated for their HIV-1reverse transcriptases inhibitoryactivities. The results of in vitro HIV-1RT kit assay showed that some of the new compounds,such as58a,59a, and64f could effectively inhibit RT activity. Among them, compounds58aand59a where ethyl group existed at5-position on N-3pyrimidine ring were the best oneswith the IC50values of3.02μM and3.06μM, respectively. Structure activity relationshipanalysis of these analogues suggested that the introduction of hydrophilic groups had littleeffect on their anti-HIV-RT activity and the N-3pyrimidine moiety on thiazolidin-4-one ringshould be more favorable to the anti-HIV activity than the C-2phenyl group.2. For the allosteric site of HIV reverse transcriptase, we degsined and synthesized a seriesof novel thiazolidin-4-one derivatives possessing alkyl amide at N-3. The evaluation ofanti-HIV activity of the new compounds is under way.