Synthesis and biological evaluations of sulfanyltriazoles as novel HIV-1 non-nucleoside reverse transcriptase inhibitors.
A novel sulfanyltriazole was discovered as an HIV-1 non-nucleoside reverse transcriptase inhibitor via HTS using a cell-based assay. Chemical modifications and molecular modeling studies were carried out to establish its SAR and understand its interactions with the enzyme. These modifications led to the identification of sulfanyltriazoles with low nanomolar potency for inhibiting HIV-1 replication and promising activities against selected NNRTI resistant mutants. These novel and potent sulfanyltriazoles could serve as advanced leads for further optimization.
Wang
Zhiwei
Z
Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA 92121, USA.
Wu
Baogen
B
Kuhen
Kelli L
KL
Bursulaya
Badry
B
Nguyen
Truc N
TN
Nguyen
Deborah G
DG
He
Yun
Y
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D024882:Drug Resistance, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013457:Sulfur Compounds / Q000737:chemistry; D013696:Temperature; D014230:Triazoles / Q000737:chemistry*; D014779:Virus Replication
D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D018894:Reverse Transcriptase Inhibitors; D013457:Sulfur Compounds; D014230:Triazoles