title: 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).
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.
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Lin
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
authors.forename: Renzhang
authors.initials: R
authors.lastname: Yan
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006577:Heterocyclic Oxides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006577:Heterocyclic Oxides; D018894:Reverse Transcriptase Inhibitors; D013829:Thiadiazines