2. Academic Validation
  3. 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)

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)

  • Bioorg Med Chem. 2008 Jan 1;16(1):157-63. doi: 10.1016/j.bmc.2007.10.013.
Yongqiang Lin 1,  Xinyong Liu,  Renzhang Yan,  Jin Li,  Christophe Pannecouque,  Myriam Witvrouw,  Erik De Clercq
Affiliations

Affiliation

  • 1 Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China.
PMID: 17964796 DOI: 10.1016/j.bmc.2007.10.013
Abstract

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 (EC(50)) of 4.0 microM and a selectivity index (SI) of >76. The structure-activity relationship (SAR) is discussed.

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