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Biaryl Ethers as Novel Non-nucleoside Reverse Transcriptase Inhibitors with Improved Potency against Key Mutant Viruses

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journal contribution
posted on 26.11.2009, 00:00 by Dai-Shi Su, John J. Lim, Elizabeth Tinney, Bang-Lin Wan, Mary Beth Young, Kenneth D. Anderson, Deanne Rudd, Vandna Munshi, Carolyn Bahnck, Peter J. Felock, Meiquing Lu, Ming-Tain Lai, Sinoeun Touch, Gregory Moyer, Daniel J DiStefano, Jessica A. Flynn, Yuexia Liang, Rosa Sanchez, Rebecca Perlow-Poehnelt, Mike Miller, Joe P. Vacca, Theresa M. Williams, Neville J. Anthony
Biaryl ethers were recently reported as potent NNRTIs. Herein we disclose a detailed SAR study that led to the biaryl ether 6. This compound possessed excellent potency against WT RT and key clinically observed RT mutants and had an excellent pharmacokinetic profile in rats, dogs, and rhesus macaques. The compound also exhibited a clean safety profile in preclinical safety studies.