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Design, Synthesis, and Biological Evaluation of Novel 3,5‐Disubstituted‐1,2,6‐Thiadiazine‐1,1‐Dione Derivatives as HIV ‐1 NNRTI s
Author(s) -
Tian Ye,
Rai Diwakar,
Zhan Peng,
Pannecouque Christophe,
Balzarini Jan,
Clercq Erik,
Liu Huiqing,
Liu Xinyong
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12160
Subject(s) - reverse transcriptase , stereochemistry , docking (animal) , chemistry , pyrimidine , human immunodeficiency virus (hiv) , structure–activity relationship , combinatorial chemistry , in vitro , molecular model , nucleoside , enzyme , ec50 , lead compound , biochemistry , biology , rna , virology , medicine , nursing , gene
On the basis of structural features, binding mode, and structure–activity relationship studies of two pyrimidine‐derived non‐nucleoside reverse‐transcriptase inhibitors, DABO s, and diaryl pyrimidines, a novel class of 1,2,6‐thiadiazine‐1,1‐dione derivatives were rationally designed using the strategies of bioisosterism and molecular hybridization, synthesized, and evaluated for their anti‐ HIV activity in MT 4 cell cultures. Three compounds were found to have moderate activity against HIV ‐1 replication with EC 50 values ranging from 23 to 32 μ m . To further confirm the binding target, compound IIg was selected to conduct an HIV ‐1 reverse‐transcriptase inhibitory assay. In addition, preliminary structure–activity relationship analysis among the newly synthesized compounds was discussed, and the binding mode of the active compound IIg was rationalized by molecular docking and physicochemical studies.