1310416-52-4Relevant articles and documents
Rational design of potent non-nucleoside inhibitors of HIV-1 reverse transcriptase
Chong, Pek,Sebahar, Paul,Youngman, Michael,Garrido, Dulce,Zhang, Huichang,Stewart, Eugene L.,Nolte, Robert T.,Wang, Liping,Ferris, Robert G.,Edelstein, Mark,Weaver, Kurt,Mathis, Amanda,Peat, Andrew
supporting information, p. 10601 - 10609 (2013/02/23)
A new series of non-nucleoside reverse transcriptase inhibitors based on an imidazole-amide biarylether scaffold has been identified and shown to possess potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus. X-ray crystallography of inhibitors bound to reverse transcriptase, including a structure of the Y188L RT protein, was used extensively to help identify and optimize the key hydrogen-bonding motif. This led directly to the design of compound 43 that exhibits remarkable antiviral activity (EC50 1 nM) against a wide range of NNRTI-resistant viruses and a favorable pharmacokinetic profile across multiple species.