title: Synthesis and anti-HIV activity evaluation of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo-[4,5-e][1,2]thiadiazines.
abstract: A series of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo[4,5-e] [1,2,4]thiadiazines (PTDs) was synthesized, structurally confirmed by spectral analysis, and evaluated for their anti-HIV activities by inhibition of HIV-induced cytopathogenicity in MT-4 cell culture. The results showed that some compounds exhibited inhibitory activity specifically against HIV-2 replication. The most active HIV-2 inhibitor was compound 7i (R1 = benzyl, R2 = 4-t-butyl-benzyl) with an EC50 value of 18.7 microM and SI=15, which may provide a useful lead for further molecular optimization.
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, PR China. epalaska@hacettepe.edu.tr
authors.forename: Xin-yong
authors.initials: XY
authors.lastname: Liu
authors.forename: Ren-zhang
authors.initials: RZ
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Molina
authors.forename: Salvador
authors.initials: S
authors.lastname: Vega
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D003499:Cyclic S-Oxides / Q000138:chemical synthesis* / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000138:chemical synthesis* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: C530136:2-benzyl-4-(4-(t-butyl)chlorobenzyl)-7-methyl-1,1,3-trioxo-2,4-dihydropyrazolo(4,5-e)(1,4)thiadiazine; D019380:Anti-HIV Agents; D003499:Cyclic S-Oxides; D011720:Pyrazoles; D013829:Thiadiazines