Synthesis and anti-HIV evaluation of novel 1,3-disubstituted thieno[3,2-c][1,2,6]thiadiazin-4(3H)-one 2,2-dioxides(TTDDs)

A series of novel 1,3-disubstituted thieno[3,2-c] [1,2,6]thiadiazin-4(3H)-one 2,2-dioxides (TTDDs), designed as non-nucleoside reverse transcriptase inhibitors (NNRTIs), was synthesized, structurally confirmed by spectral analysis and evaluated for their anti-HIV-1 activities by inhibition of HIV-1(IIIB)-induced cytopathogenicity in MT-4 cell culture. The results showed that TTDD analogues exhibited marked potency as anti-HIV-1 agents. The most active and selective compound was 1-(3-cyano)benzyl-3-benzyl-thieno[3,2-c][1,2,6]thiadiazin-4(3H)-one 2,2-dioxide (5f) with a 50% effective concentration (EC50) of 4.0 μM and a selectivity index (SI) of >76. The structure–activity relationship (SAR) is discussed.

Novel TTDDs were designed, synthesized and evaluated for their anti-HIV-1 activities in cell culture, and proved to be both potent and selective as HIV-1 inhibitors. The structure–activity relationship (SAR) is discussed.Figure optionsDownload as PowerPoint slide