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- Title
Design, Synthesis, and Biological Evaluation of Novel 3,5-Disubstituted-1,2,6-Thiadiazine-1,1-Dione Derivatives as HIV-1 NNRTIs.
- Authors
Tian, Ye; Rai, Diwakar; Zhan, Peng; Pannecouque, Christophe; Balzarini, Jan; Clercq, Erik; Liu, Huiqing; Liu, Xinyong
- Abstract
On the basis of structural features, binding mode, and structure-activity relationship studies of two pyrimidine-derived non-nucleoside reverse-transcriptase inhibitors, DABOs, 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 MT4 cell cultures. Three compounds were found to have moderate activity against HIV-1 replication with EC50 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.
- Subjects
PYRIMIDINES; HETEROCYCLIC compounds; CELL culture; SPECIES hybridization; REVERSE transcriptase inhibitors; CYTOLOGICAL techniques
- Publication
Chemical Biology & Drug Design, 2013, Vol 82, Issue 4, p384
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12160