68032-82-6Relevant academic research and scientific papers
CATECHOL DIETHERS AS POTENT ANTI-HIV AGENTS
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Page/Page column 48, (2013/04/25)
The present invention is directed to novel catechol diether compounds, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV 1 and 2 and/or sec
Computationally-guided optimization of a docking hit to yield catechol diethers as potent anti-HIV agents
Bollini, Mariela,Domaoal, Robert A.,Thakur, Vinay V.,Gallardo-Macias, Ricardo,Spasov, Krasimir A.,Anderson, Karen S.,Jorgensen, William L.
supporting information; experimental part, p. 8582 - 8591 (2012/02/02)
A 5-μM docking hit has been optimized to an extraordinarily potent (55 pM) non-nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (FEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity. (Figure presented)
