Discovery of phenylaminopyridine derivatives as novel HIV-1 non-nucleoside reverse transcriptase inhibitors

ACS Medicinal Chemistry Letters

Volumn 3, Issue 8, 2012, Pages 678-682

  Kim, Junwon ^a   Lee, Doohyun ^b   Park, Changmin ^a   So, Wonyoung ^a   Jo, Mina ^a   Ok, Taedong ^a   Kwon, Jeongjin ^a   Kong, Sunju ^b   Jo, Suyeon ^a   Kim, Youngmi ^b   Choi, Jihyun ^a   Kim, Hyoung Cheul ^a   Ko, Yoonae ^b   Choi, Inhee ^b   Park, Youngsam ^b   Yoon, Jaewan ^b   Ju, Moon Kyeong ^b   Kim, Junghwan ^b   Han, Sung Jun ^b   Kim, Tae Hee ^b,c   Cechetto, Jonathan ^b   Nam, Jiyoun ^b   Sommer, Peter ^b   Liuzzi, Michel ^b   Lee, Jinhwa ^b   No, Zaesung ^b   more..

^a Institute Pasteur Korea   (South Korea)

^b Institut Pasteur Korea   (South Korea)

^c Yonsei University   (South Korea)

Author keywords

HIV 1; non nucleoside reverse transcriptase inhibitors; reverse transcriptase; synthesis; X ray crystal structure

Indexed keywords

AMINOPYRIDINE DERIVATIVE; FUNCTIONAL GROUP; NEVIRAPINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG CONFORMATION; DRUG SOLUBILITY; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HUMAN IMMUNODEFICIENCY VIRUS 1; IN VITRO STUDY; NONHUMAN; PRIORITY JOURNAL; VIRUS GENE;

EID: 84864982700     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml300146q     Document Type: Article

References (23)

1. Xu, H.; Lv, M. Developments of indoles as anti-HIV-1 inhibitors Curr. Pharm. Des. 2009, 15, 2120-2148
2. De Clercq, E. Highlights in the discovery of antiviral drugs: A personal retrospective J. Med. Chem. 2010, 53, 1438-1450
3. Mehellou, Y.; De Clercq, E. Twenty-six years of anti-HIV drug discovery: Where do we stand and where do we go? J. Med. Chem. 2010, 53, 521-538
4. Mocroft, A.; Ledergerber, B.; Katlama, C.; Kirk, O.; Reiss, P.; d'Arminio Monforte, A.; Knysz, B.; Dietrich, M.; Phillips, A. N.; Lundgren, J. D. Decline in the AIDS and death rates in the EuroSIDA study: An observational study Lancet 2003, 362, 22-29 (Pubitemid 36835816)
5. Panos, G.; Samonis, G.; Alexiou, V. G.; Kavarnou, G. A.; Charatsis, G.; Falagas, M. E. Mortality and morbidity of HIV infected patients receiving HAART: A cohort study Curr. HIV Res. 2008, 6, 257-260 (Pubitemid 352024678)
6. de Bethune, M.-P. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery, development, and use in the treatment of HIV-1 infection: A review of the last 20 years (1989-2009) Antiviral Res. 2010, 85, 75-90
7. Paredes, R.; Clotet, B. Clinical management of HIV-1 resistance Antiviral Res. 2010, 85, 245-265
8. Kiertiburanakul, S.; Sungkanuparph, S. Emerging of HIV Drug Resistance: Epidemiology, Diagnosis, Treatment and Prevention Curr. HIV Res. 2009, 7, 273-278
9. Esplugues, J. V.; Blas-Garcia, A.; Apostolova, N. Twenty Years of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Time to Reevaluate their Toxicity Curr. Med. Chem. 2011, 18, 2186-2195
10. Hawkins, T. Understanding and managing the adverse effects of antiretroviral therapy Antiviral Res. 2010, 85, 201-209
11. Li, D.; Zhan, P.; De Clercq, E.; Liu, X. Strategies for the Design of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Lessons from the Development of Seven Representative Paradigms J. Med. Chem. 2012, 55, 3595-3613
12. Heller, S. T.; Natarajan, S. R. 1,3-Diketones from acid chlorides and ketones: A rapid and general one-pot synthesis of pyrazoles Org. Lett. 2006, 8, 2675-2678 (Pubitemid 44085839)
13. Fleming, F. F.; Yao, L.; Ravikumar, P. C.; Funk, L.; Shook, B. C. Nitrile-containing pharmaceuticals: efficacious roles of the nitrile pharmacophore J. Med. Chem. 2010, 53, 7902-7917
14. Liu, X. Y.; Chen, X. W.; Zhan, P.; Li, D. Y.; De Clercq, E. Recent Advances in DAPYs and Related Analogues as HIV-1 NNRTIs Curr. Med. Chem. 2011, 18, 359-376
15. Lansdon, E. B.; Brendza, K. M.; Hung, M.; Wang, R.; Mukund, S.; Jin, D. B.; Birkus, G.; Kutty, N.; Liu, X. H. Crystal Structures of HIV-1 Reverse Transcriptase with Etravirine (TMC125) and Rilpivirine (TMC278): Implications for Drug Design J. Med. Chem. 2010, 53, 4295-4299
16. Jamieson, C.; Moir, E. M.; Rankovic, Z.; Wishart, G. Medicinal chemistry of hERG optimizations: Highlights and hang-ups J. Med. Chem. 2006, 49, 5029-5046 (Pubitemid 44260200)
17. Kazmierski, W. M.; Anderson, D. L.; Aquino, C.; Chauder, B. A.; Duan, M.; Ferris, R.; Kenakin, T.; Koble, C. S.; Lang, D. G.; McIntyre, M. S.; Peckham, J.; Watson, C.; Wheelan, P.; Spaltenstein, A.; Wire, M. B.; Svolto, A.; Youngman, M. Novel 4,4-disubstituted piperidine-based C-C chemokine receptor-5 inhibitors with high potency against human immunodeficiency virus-1 and an improved human ether-a-go-go related gene (hERG) profile J. Med. Chem. 2011, 54, 3756-3767
18. Tucker, T. J.; Sisko, J. T.; Tynebor, R. M.; Williams, T. M.; Felock, P. J.; Flynn, J. A.; Lai, M.-T.; Liang, Y.; McGaughey, G.; Liu, M.; 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. 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
19. Dickinson, L.; Khoo, S.; Back, D. Pharmacokinetics and drug-drug interactions of antiretrovirals: An update Antiviral Res. 2010, 85, 176-189
20. Mills, J. B.; Rose, K. A.; Sadagopan, N.; Sahi, J.; de Morais, S. M. Induction of drug metabolism enzymes and MDR1 using a novel human hepatocyte cell line J. Pharmacol. Exp. Ther. 2004, 309, 303-309 (Pubitemid 38393143)
21. Ripp, S. L.; Mills, J. B.; Fahmi, O. A.; Trevena, K. A.; Liras, J. L.; Maurer, T. S.; de Morais, S. M. Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction Drug Metab. Dispos. 2006, 34, 1742-1748 (Pubitemid 44427477)
22. The co-crystal structure was obtained from Proteros Biostructures; http://www.proteros.de/.
23. Das, K.; Clark, A. D.; Lewi, P. J.; Heeres, J.; de Jonge, M. R.; Koymans, L. M. H.; Vinkers, H. M.; Daeyaert, F.; Ludovici, D. W.; Kukla, M. J.; De Corte, B.; Kavash, R. W.; Ho, C. Y.; Ye, H.; Lichtenstein, M. A.; Andries, K.; Pauwels, R.; de Béthune, M. -P.; Boyer, P. L.; Clark, P.; Hughes, S. H.; Janssen, P. A. J.; Eddy, A. Roles of Conformational and Positional Adaptability in Structure-Based Design of TMC125-R165335 (Etravirine) and Related Non-nucleoside Reverse Transcriptase Inhibitors That Are Highly Potent and Effective against Wild-Type and Drug-Resistant HIV-1 Variants J. Med. Chem. 2004, 47, 2550-2560 (Pubitemid 38580092)