920036-12-0Relevant articles and documents
Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead
Ippolito, Joseph A.,Niu, Haichan,Bertoletti, Nicole,Carter, Zachary J.,Jin, Shengyan,Spasov, Krasimir A.,Cisneros, José A.,Valhondo, Margarita,Cutrona, Kara J.,Anderson, Karen S.,Jorgensen, William L.
, p. 249 - 255 (2021/01/26)
Covalent inhibitors of wild-type HIV-1 reverse transcriptase (CRTIs) are reported. Three compounds derived from catechol diether non-nucleoside inhibitors (NNRTIs) with addition of a fluorosulfate warhead are demonstrated to covalently modify Tyr181 of HIV-RT. X-ray crystal structures for complexes of the CRTIs with the enzyme are provided, which fully demonstrate the covalent attachment, and confirmation is provided by appropriate mass shifts in ESI-TOF mass spectra. The three CRTIs and six noncovalent analogues are found to be potent inhibitors with both IC50 values for in vitro inhibition of WT RT and EC50 values for cytopathic protection of HIV-1-infected human T-cells in the 5-320 nM range.
The design and synthesis of diaryl ether second generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with enhanced potency versus key clinical mutations
Tucker, Thomas J.,Saggar, Sandeep,Sisko, John T.,Tynebor, Robert M.,Williams, Theresa M.,Felock, Peter J.,Flynn, Jessica A.,Lai, Ming-Tain,Liang, Yuexia,McGaughey, Georgia,Liu, Meiquing,Miller, Mike,Moyer, Gregory,Munshi, Vandna,Perlow-Poehnelt, Rebecca,Prasad, Sridhar,Sanchez, Rosa,Torrent, Maricel,Vacca, Joseph P.,Wan, Bang-Lin,Yan, Youwei
, p. 2959 - 2966 (2008/12/23)
Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations.
