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.
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.
Liu
Xin-yong
XY
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, PR China. epalaska@hacettepe.edu.tr
Yan
Ren-zhang
RZ
Wang
Yan
Y
Zhan
Peng
P
De Clercq
Erik
E
Pannecouque
Christophe
C
Witvrouw
Myriam
M
Molina
Maria Teresa
MT
Vega
Salvador
S
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
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