Biaryl ethers as potent allosteric inhibitors of reverse transcriptase and its key mutant viruses: Aryl substituted pyrazole as a surrogate for the pyrazolopyridine motif

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 15, 2010, Pages 4328-4332

  Su, Dai Shi ^a,b   Lim, John J ^a   Tinney, Elizabeth ^a   Tucker, Thomas J ^a   Saggar, Sandeep ^a   Sisko, John T ^a   Wan, Bang Lin ^a   Young, Mary Beth ^a   Anderson, Kenneth D ^a   Rudd, Deanne ^a   Munshi, Vandna ^a   Bahnck, Carolyn ^a   Felock, Peter J ^a   Lu, Meiquing ^a   Lai, Ming Tain ^a   Touch, Sinoeun ^a   Moyer, Gregory ^a   Distefano, Daniel J ^a   Flynn, Jessica A ^a   Liang, Yuexia ^a   Sanchez, Rosa ^a   Perlow Poehnelt, Rebecca ^a   Miller, Mike ^a   Vacca, Joe P ^a   Williams, Theresa M ^a   Anthony, Neville J ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

^b GLAXOSMITHKLINE   (United States)

Author keywords

Aryl substituted pyrazoles; Mutant virus; Non nucleoside reverse transcriptase inhibitors (NNRTI); Structural activity relationship (SAR); Surrogate for pyrazolopyridine

Indexed keywords

MK 4965; RNA DIRECTED DNA POLYMERASE INHIBITOR; TELOMERASE REVERSE TRANSCRIPTASE; UNCLASSIFIED DRUG;

ALLOSTERISM; ANIMAL EXPERIMENT; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; DRUG CLEARANCE; DRUG DESIGN; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG STRUCTURE; DRUG SYNTHESIS; EXPERIMENTAL DOG; HUMAN IMMUNODEFICIENCY VIRUS 1; IC 50; NONHUMAN; PROTEIN MOTIF; RAT; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; VIRUS MUTANT; WILD TYPE;

ALLOSTERIC REGULATION; ANIMALS; ANTI-HIV AGENTS; DOGS; ETHERS; HIV REVERSE TRANSCRIPTASE; HUMANS; MUTATION; PYRAZOLES; PYRIDINES; RATS; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 77955426207     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.06.083     Document Type: Article

References (8)

1. D.-S. Su, J.J. Lim, E. Tinney, B.-L. Wan, M.B. Young, K.D. Anderson, D. Rudd, V. Munshi, C. Bahnck, P.J. Felock, M. Lu, M.-T. Lai, S. Touch, G. Moyer, D.J. DiStefano, J.A. Flynn, Y. Liang, R. Sanchez, R. Perlow-Poehnelt, M. Miller, J.P. Vacca, T.M. Williams, and N.J. Anthony J. Med. Chem. 52 2009 7163
2. T.J. Tucker, J.T. Sisko, R.M. Tynebor, T.M. Williams, P.J. Felock, J.A. Flynn, M.-T. Lai, Y. Liang, G. McGaughey, M. Liu, M. Miller, G. Moyer, V. Munshi, R. Perlow-Poehnell, S. Prasad, J.C. Reid, R. Sanchez, M. Torrent, J.P. Vacca, B.-L. Wan, and Y. Yan J. Med. Chem. 51 2008 6503
3. T.J. Tucker, S. Saggar, J.T. Sisko, R.M. Tynebor, T.M. Williams, P.J. Felock, J.A. Flynn, M.-T. Lai, Y. Liang, G. McGaughey, M. Liu, M. Miller, G. Moyer, V. Munshi, R. Perlow-Poehnell, S. Prasad, R. Sanchez, M. Torrent, J.P. Vacca, B.-L. Wan, and Y. Yan Bioorg. Med. Chem. Lett. 18 2008 2959
4. Z.K. Sweeney, S.F. Harris, N. Arora, H. Javanbakht, Y. Li, J. Fretland, J.P. Davidson, J.R. Biledeau, S.K. Gleason, D. Hirschfeld, J.J. Kennedy-Smith, T. Mirazadegan, R. Roetz, M. Smith, S. Sperry, J.M. Suh, J. Wu, S. Tsing, A.G. Villasenor, A. Paul, G. Su, G. Heilek, J.Q. Hang, A.S. Zhou, J.A. Jernelius, F.-J. Zhang, and K. Klumpp J. Med. Chem. 51 2008 7449
5. T.R. Elworthy, J.P. Dunn, J.H. Hogg, G. Lam, Y.D. Saito, T.M.A.C. Silva, D. Stefanidis, W. Woroniecki, E. Zhornisky, A.S. Zhou, and K. Klumpp Bioorg. Med. Chem. Lett. 18 2008 6344
6. i (nM): 0.4/8.5/0.3 (WT/K103N/Y181C)).
7. 95 (nM): 4.3/38 (WT, 10% FBS/50% NHS), 232 (K103N, 10% FBS), 8.0 (Y181C, 10% FBS), and 272 (K103N/Y181C, 10% FBS)).
8. Assays performed by Monogram Bioscience, San Francisco, CA. Values are the average of two determinations. Detailed assay protocols are available at: http://www.monogramhiv.com/assays/hcp/phenolHIVTechnology.aspx.