HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Design, Synthesis And Antiviral Evaluation Of Novel 1,3-Disubstituted Thieno[3,2-e][2,1,3] Thiadiazin-4-one 2,2-Dioxides (TTDDs)

Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV). The reverse transcriptase (RT) plays a crucial role in the replication of HIV life cycle, and is responsible for the conversion of the single-stranded RNA viral genome into double-stranded DNA that subsequently integrates into the host DNA.Because of the distinct function of RT in the virus life cycle, it is one of the important targets of antiviral therapy. Two main classes of RT inhibitors have been hitherto discovered: (1) nucleoside reverse transcriptase inhibitors (NRTIs), which compete with natural substrates by mimicking the normal deoxynucleoside triphosphate and function as chain terminators, and (2) the non-nucleoside reverse transcriptase inhibitors (NNRTIs), which inhibit the enzyme by an non-competitively allosteric mechanism involving binding to a site adjacent to the deoxyribonucleoside triphosphate binding site of the enzyme. Both of them have been found to be effective in halting the enzymatic function of RT.Substituted 1,1,3-trioxo-2H,4H-thieno[3,4-e] [1,2,4]thiadiazine derivatives (TTDs) represented a new class of specific HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). The prototype of these compounds was QM96521 and QM96625 (EC₅₀ 0.1μM and SIM 190). Also, reported to be novel anti-HIV-1 agents, 1,3-disubstituted-2,1, 3-benzothiadiazin-4-one 2, 2-dioxides (BTDs) inhibited...