Design, synthesis, and evaluation of diarylpyridines and diarylanilines as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

Journal of Medicinal Chemistry

Volumn 53, Issue 23, 2010, Pages 8287-8297

  Tian, Xingtao ^a,f   Qin, Bingjie ^a   Wu, Zhiyuan ^a   Wang, Xiaofeng ^a   Lu, Hong ^b   Morris Natschke, Susan L ^d   Chen, Chin Ho ^c   Jiang, Shibo ^b   Lee, Kuo Hsiung ^d,e   Xie, Lan ^a  

^a BEIJING INSTITUTE OF PHARMACOLOGY AND TOXICOLOGY   (China)

^b NEW YORK BLOOD CENTER   (United States)

^c DUKE UNIVERSITY MEDICAL CENTER   (United States)

^d University of North Carolina   (United States)

^e CHINA MEDICAL UNIVERSITY   (Taiwan)

^f RESEARCH INSTITUTE OF CHEMICAL DEFENSE   (China)

Author keywords

[No Author keywords available]

Indexed keywords

(4' CYANOPHENYL) 4 (4'' CYANOVINYL 2'',6'' DIMETHYL) PHENOXYBENZENE 1,2 DIAMINE; (4' CYANOPHENYL) 5 (4'' CYANOVINYL 2'',6'' DIMETHYL) PHENOXYBENZENE 4 NITRO 1,2 DIAMINE; (4'CYANOPHENYL) 6 (4'' CYANOVINYL 2'',6'' DIMETHYL) PHENOXYPYRIDIN 2,3 DIAMINE; ANTIVIRUS AGENT; ETRAVIRINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG DESIGN; DRUG EFFICACY; DRUG RESISTANCE; DRUG SCREENING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION;

ANILINE COMPOUNDS; CELL LINE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DRUG DESIGN; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; PYRIDINES; REVERSE TRANSCRIPTASE INHIBITORS;

EID: 78649854734     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100738d     Document Type: Article

References (23)

1. Esnouf, R.; Ren, J.; Ross, C.; Jones, Y.; Stammers, D.; Stuart, D. Mechanism of inhibition of reverse transcriptase by non-nucleoside inhibitors Nature Struct. Biol. 1995, 2, 303-308
2. Pauwels, R. New non-nucleoside reverse transcriptase inhibitors (NNRTIs) in development for the treatment of HIV infections Curr. Opin. Pharmacol. 2004, 4, 437-446
3. Sweeney, Z. K.; Klumpp, K. Improving non-nucleoside reverse trancriptase inhibitors for first-line treatment of HIV infection: the development pipeline and recent clinical data Curr. Opin. Drug Discovery Dev. 2008, 11 (4) 458-470
4. Minudo, J. J.; Haubrich, R. Entravirine: a second-generation NNRTI for treatment- experienced adults with resistant HIV-1 infection Futur. HIV Ther. 2008, 2 (6) 525-537
5. Sarafianos, S. G.; Marchand, B.; Das, K.; Himmel, D. M.; Parniak, M. A.; Hughes, S. H.; Arnold, E. Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition J. Mol. Biol. 2009, 385, 693-713
6. Rossotti, R.; Rusconi, S. Efficacy and resistance of recently developed non-nucleoside reverse transcriptase inhibitors for HIV-1 HIV Ther. 2009, 3 (1) 63-77
7. Lai, M. T.; Munshi, V.; Touch, S.; Tynebor, R. M.; Tucker, T. J.; McKenna, P. M.; Williams, T. M.; DiStefano, D. J.; Hazuda, D. J.; Miller, M. D. Antiviral activity of MK-4965, a novel non-nucleoside reverse transcriptase inhibitor Antimicrob. Agents Chemother. 2009, 53 (6) 2424-2431
8. Tucker, T. J.; Sisko, J. T.; Tynebor, R. M.; Williams, T. M.; Felock, P. J.; Flynn, J. A.; Lai, M. T.; Liang, Y. X.; Gaughey, G. M.; Liu, M. Q.; Miller, M.; Moyer, G.; Munshi, V.; Perlow-Poehnelt, R.; Prasad, S.; Reid, J. C.; Sanchez, R.; Torrent, M.; Vacca, J. P.; Wan, B. L.; Yan, Y. W. Discovery of 3-{5-[(6-Amino-1 H -pyrazolo[3,4- b ]pyridine-3-yl)methoxy]-2-chlorophenoxy}-5- chlorobenzonitrile (MK-4965): a potent, orally bioavailable HIV-1 non-nucleoside reverse transcriptase inhibitor with improved potency against key mutant viruses J. Med. Chem. 2008, 51, 6503-6511
9. Ripamonti, D.; Maggiolo, F. Rilpivirine, a non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infection Curr. Opin. Invest. Drugs 2008, 9 (8) 899-912
10. Pecora Fulco, P.; McNicholl, I. R. Ereavirine and rilpivirine: non-nucleoside reverse transcriptase inhibitors with activity against human immunodeficiency virus type 1 strains resistant to previous non-nucleoside agents Pharmacotherapy 2009, 29 (3) 281-294
11. Tian, X. T.; Qin, B. J.; Lu, H.; Lai, W.; Jiang, S.; Lee, K. H.; Chen, C. H.; Xie, L. Discovery of diarylpyridine derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 3482-5485
12. Qin, B. J.; Jiang, X. K.; Lu, H.; Tian, X. T.; Barbault, F.; Huang, L.; Qian, K.; Chen, C. H.; Huang, R.; Jiang, S.; Lee, K. H.; Xie, L. Diarylaniline derivatives as a distinct class of HIV-1 non-nucleoside reverse transcriptase inhibitors J. Med. Chem. 2010, 53, 4906-4916
13. De Corte, B. L. From 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1- jk ](1,4)benzodiazepine-2(1 H)-one (TIBO) to etravirine (TMC125): fifteen years of research on non-nucleoside inhibitors of HIV-1 reverse transcriptase J. Med. Chem. 2005, 48, 1689-1696
14. Das, K.; Bauman, J. D.; Clark, A. D. J.; Frenkel, Y. V.; Lewi, P. J.; Shatkin, A. J.; Hughes, S. H.; Arnold, E. High-resolution structures of HIV-1 reverse transcriptase/TMC-278 complexes: strategic flexibility explains potency against resistance mutations Proc. Natl. Acad. Sci. U.S.A. 2008, 105 (5) 1466-1471
15. Redemann, C. T.; Redemann, C. E. 5-Amino-2,3-dihydro-1,4-phthalazinedione Org. Synth. 1949, 29, 8-9
16. Mordant, C.; Schmitt, B.; Pasquier, E.; Demestre, C.; Queguiner, L.; Masungi, C.; Peeters, A.; Smeulders, L.; Bettens, E.; Hertogs, K.; Heeres, J.; Lewi, P.; Guillemont, J. Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains E. J. Med. Chem. 2007, 42, 567-569
17. Andries, K.; Azijn, H.; Thielemans, T.; Ludovici, D.; Kukla, M.; Heeres, J.; Janssen, P.; De Corte, B.; Vingerhoets, J.; Pauwels, R.; de Bethune, M. P. TMC125, a novel next-generation non-nucleoside reverse transcriptase inhibitor active against non-nucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1 Antimicrob. Agents Chemother. 2004, 48, 4680-4686
18. Lansdon, E. B.; Broendza, K. M.; Hung, M.; Wang, R.; Mukund, S.; Jin, D.; Birkus, G.; Kutty, N.; Liu, X. Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design J. Med. Chem. 2010, 53, 4295-4299
19. Obiol-Pardo, C.; Rubio-Martinez, J. Comparative evaluation of MMPBSA and XSCORE to compute binding free energy in XIA-peptide complexes J. Chem. Inf. Model. 2007, 47, 134-142
20. Jiang, S.; Lu, H.; Liu, S.; Zhao, Q.; He, Y.; Debnath, A. K. N-Substituted pyrrole derivatives as novel human immunodeficiency virus type 1 entry inhibitors that interfere with the gp41 six-helix bundle formation and block virus fusion Antimicrob. Agents Chemother. 2004, 48, 4349-4359
21. Chou, T. C.; Talalay, P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors Adv. Enzyme Regul. 1984, 22, 27-55
22. Dang, Z.; Lai, W.; Qian, K.; Lee, K. H.; Chen, C. H.; Huang, L. Betulinic Acid Derivatives as Human Immunodeficiency Virus Type 2 (HIV-2) Inhibitors J. Med. Chem. 2009, 52, 7887-7891
23. Zhao, Q.; Ma, L.; Jiang, S.; Lu, H.; Liu, S.; He, Y.; Strick, N.; Neamati, N.; Debnath, A. K. Identification of N -phenyl- N ′-(2,2,6,6- tetramethylpiperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4 Virology 2005, 339, 213-225