Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 2: Discovery of novel [1,2,4]Triazolo[1,5-a]pyrimidines using a structure-guided core-refining approach

European Journal of Medicinal Chemistry

Volumn 85, Issue , 2014, Pages 293-303

  Wang, Liu ^a   Tian, Ye ^a   Chen, Wenmin ^a   Liu, Hong ^a   Zhan, Peng ^a   Li, Dongyue ^a   Liu, Huiqing ^a   De Clercq, Erik ^b   Pannecouque, Christophe ^b   Liu, Xinyong ^a  

^a SHANDONG UNIVERSITY   (China)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

anti HIV activities; Bridgehead nitrogen heterocycle; DAPY; Molecular modeling; Structure activity relationships; 1,2,4 Triazolo 1,5 a pyrimidine

Indexed keywords

4 [5 (2,4,6 TRICHLOROPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 7 YLAMINO]BENZONITRILE; 4 [5 (2,4,6 TRIFLUOROPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 7 YLAMINO]BENZONITRILE; 4 [5 (2,6 DIMETHYLPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 7 YLAMINO]BENZONITRILE; 4 [5 (4 BROMO 2,6 DIMETHYLPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 7 YLAMINO]BENZONITRILE; 4 [5 (MESITYLOXY)[1,2,4]TRIAZOLO[1,5A]PYRIMIDIN 7 YLAMINO]BENZONITRILE; 4 [[5 [(4 CYANOPHENYL)AMINO][1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 7 YL]OXY] 3,5 DIMETHYLBENZONITRILE; 4 [[7 (2,4,6 TRIBROMOPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]AMINO]BENZONITRILE; 4 [[7 (2,6 DIBROMO 4 METHYLPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]AMINO]BENZONITRILE; 4 [[7 (2,6 DICHLOROPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]AMINO]BENZONITRILE; 4 [[7 (2,6 DIMETHYLPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]AMINO]BENZONITRILE; 4 [[7 (4 BROMO 2,6 DIMETHYLPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]AMINO]BENZONITRILE; 4 [[7 (4 CHLORO 2,6 DIMETHYLPHENOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]AMINO]BENZONITRILE; 4 [[7 (MESITYLAMINO)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]AMINO]BENZONITRILE; 4 [[7 (MESITYLOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]AMINO]BENZONITRILE; 4 [[7 [(2,6 DIMETHYLPHENYL)AMINO][1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]AMINO]BENZONITRILE; 7 (MESITYLOXY) N (4 METHOXYPHENYL)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 AMINE; 7 (MESITYLOXY) N (4 NITROPHENYL)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 AMINE; 7 (MESITYLOXY) N (4 TOLYL)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 AMINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DELAVIRDINE; ETRAVIRINE; FUSED CARBON NITROGEN HETEROCYCLE; N (4 CHLOROPHENYL) 7 (MESITYLOXY)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 AMINE; NEVIRAPINE; NITROGEN; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; [1,2,4]TRIAZOLO[1,5 A]PYRIMIDINE DERIVATIVE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG EFFICACY; DRUG STRUCTURE; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR MODEL; NONHUMAN; STRUCTURE ACTIVITY RELATION; WILD TYPE; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; DRUG EFFECTS; ENZYMOLOGY; GENETICS; MUTATION; PROTEIN CONFORMATION;

DRUG DESIGN; HIV REVERSE TRANSCRIPTASE; HIV-1; MODELS, MOLECULAR; MUTATION; NITROGEN; PROTEIN CONFORMATION; PYRIMIDINES; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84905698576     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.07.104     Document Type: Article

References (31)

1. E. De Clercq The design of drugs for HIV and HCV Nat. Rev. Drug. Discov. 6 2007 1001 1018 (Pubitemid 350213865)
2. P. Zhan, and X. Liu Novel HIV-1 non-nucleoside reverse transcriptase inhibitors: a patent review (2005-2010) Expert Opin. Ther. Patents 21 2011 717 796
3. P. Zhan, X. Liu, and Z. Li Recent advances in the discovery and development of novel HIV-1 NNRTI platforms: 2006-2008 update Curr. Med. Chem. 16 2009 2876 2889
4. Y. Song, P. Zhan, and X. Liu Recent advances in the discovery and development of novel HIV-1 NNRTI platforms (Part II): 2009-2013 update Curr. Med. Chem. 21 2013 329 355
5. P. Zhan, X. Liu, Z. Li, C. Pannecouque, and E. De Clercq Design strategies of novel NNRTIs to overcome drug resistance Curr. Med. Chem. 16 2009 3903 3917
6. P. Zhan, X. Chen, D. Li, Z. Fang, E. De Clercq, and X. Liu HIV-1 NNRTIs: structural diversity, pharmacophore similarity, and implications for drug design Med. Res. Rev. 33 2013 E1 E72
7. D. Li, P. Zhan, E. De Clercq, and X. Liu Strategies for the design of HIV-1 non-nucleoside reverse transcriptase inhibitors: lessons from the development of seven representative paradigms J. Med. Chem. 55 2012 3595 3613
8. P. Sax FDA approval: etravirine AIDS Clin. Care 20 2008 17 18
9. M. Schöller-Gyüre, T.N. Kakuda, G. De Smedt, H. Vanaken, M.P. Bouche, M. Peeters, B. Woodfall, and R.M. Hoetelmans A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV-negative volunteers Br. J. Clin. Pharmacol. 66 2008 508 516
10. E. Seminari, A. Castagna, and A. Lazzarin Etravirine for the treatment of HIV infection Expert Rev. Anti-infective Ther. 6 2008 427 433
11. B.C. Johnson, G.T. Pauly, G. Rai, D. Patel, J.D. Bauman, H.L. Baker, K. Das, J.P. Schneider, D.J. Maloney, and E. Arnold A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants Retrovirology 9 2012 99
12. D. Li, P. Zhan, H. Liu, C. Pannecouque, J. Balzarini, E. De Clercq, and X. Liu Synthesis and biological evaluation of pyridazine derivatives as novel HIV-1 NNRTIs Bioorg. Med. Chem. 21 2013 2128 2134
13. X. Li, W. Chen, Y. Tian, H. Liu, P. Zhan, C. Pannecouque, J. Balzarini, E. De Clercq, and X. Liu Discovery of novel diarylpyrimidines as potent HIV NNRTIs via a structure-guided core-refining approach Eur. J. Med. Chem. 80 2013 112 121
14. J. Wang, P. Zhan, Z. Li, E. De Clercq, C. Pannecouque, J. Balzarini, and X. Liu Synthesis and biological evaluation of substituted nitropyridine derivatives as potent HIV-1 non-nucleoside reverse transcriptase inhibitors Eur. J. Med. Chem. 76 2013 531 538
15. A. Raney, R. Hamatake, W. Xu, J. Vernier, J. Girardet, P. Weingarten, D. Zhou, H. Kim, R. Dick, and L. Yeh RDEA427 and RDEA640 are novel NNRTIs with potent anti-HIV activity against NNRTI-resistant viruses 15th Conference on Retroviruses and Opportunistic Infections (CROI) 2008 3 6
16. E.H. Kerns, and L. Di Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization 2008 Elsevier London
17. Deepak Dalvie, Ping Kang, Cho-Ming Loi, Lance Goulet, and S. Nair Influence of heteroaromatic rings on ADME properties of drugs D.A. Smith, Metabolism, Pharmacokinetics and Toxicity of Functional Groups: Impact of Chemical Building Blocks on ADMET 2010 Royal Society of Chemistry London 328 369
18. Y. Song, P. Zhan, Q. Zhang, and X. Liu Privileged scaffolds or promiscuous binders: a glance of pyrrolo [2, 1-f][1, 2, 4] triazines and related bridgehead nitrogen heterocycles in medicinal chemistry Curr. Pharm. Des. 19 2013 1528 1548
19. R. Gujjar, F. El Mazouni, K.L. White, J. White, S. Creason, D.M. Shackleford, X. Deng, W.N. Charman, I. Bathurst, J. Burrows, D.M. Floyd, D. Matthews, F.S. Buckner, S.A. Charman, M.A. Phillips, and P.K. Rathod Lead optimization of aryl and aralkyl amine-based triazolopyrimidine inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with antimalarial activity in mice J. Med. Chem. 54 2011 3935 3949
20. L. McKendry Preparation of carbon-14 labeled N-(2, 6-dichloro-3- methylphenyl)-5, 7-dimethoxy [1, 2, 4] triazolo [1,5-a] pyrimidine-2-sulfonamide J. Label. Compd. Radiopharm. 39 1997 231 240
21. N. Zhang, S. Ayral-Kaloustian, T. Nguyen, J. Afragola, R. Hernandez, J. Lucas, J. Gibbons, and C. Beyer Synthesis and SAR of [1,2,4] triazolo [1,5-a] pyrimidines, a class of anticancer agents with a unique mechanism of tubulin inhibition J. Med. Chem. 50 2007 319 327 (Pubitemid 46147711)
22. C.M. Richardson, D.S. Williamson, M.J. Parratt, J. Borgognoni, A.D. Cansfield, P. Dokurno, G.L. Francis, R. Howes, J.D. Moore, J.B. Murray, A. Robertson, A.E. Surgenor, and C.J. Torrance Triazolo [1,5-a] pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR Bioorg. Med. Chem. Lett. 16 2006 1353 1357 (Pubitemid 43143021)
23. Z. Zeng, Q. He, Y. Liang, X. Feng, F. Chen, E.D. Clercq, J. Balzarini, and C. Pannecouque Hybrid diarylbenzopyrimidine non-nucleoside reverse transcriptase inhibitors as promising new leads for improved anti-HIV-1 chemotherapy Bioorg. Med. Chem. 18 2010 5039 5047
24. M. Popovic, M.G. Sarngadharan, E. Read, and R.C. Gallo Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS Science 224 1984 497 500 (Pubitemid 14134740)
25. F. Barré-Sinoussi, J.-C. Chermann, F. Rey, M.T. Nugeyre, S. Chamaret, J. Gruest, C. Dauguet, C. Axler-Blin, F. Vézinet-Brun, and C. Rouzioux Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS) Science 220 1983 868 871
26. I. Miyoshi, H. Taguchi, I. Kubonishi, S. Yoshimoto, Y. Ohtsuki, Y. Shiraishi, and T. Akagi Type C virus-producing cell lines derived from adult T cell leukemia Gann Monogr. 28 1982 19 228
27. R. Pauwels, J. Balzarini, M. Baba, R. Snoeck, D. Schols, P. Herdewijn, J. Desmyter, and E. De Clercq Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds J. Virol. Methods. 20 1988 309 321
28. C. Pannecouque, D. Daelemans, and E. De Clercq Tetrazolium-based colorimetric assay for the detection of HIV replication inhibitors: revisited 20 years later Nat. Protoc. 3 2008 427 434 (Pubitemid 351384256)
29. X.D. Ma, S.Q. Yang, S.X. Gu, Q.Q. He, F.E. Chen, E. De Clercq, J. Balzarini, and C. Pannecouque Synthesis and anti-HIV activity of aryl-2-[(4-cyanophenyl)amino]-4-pyrimidinone hydrazones as potent non-nucleoside reverse transcriptase inhibitors ChemMedChem 6 2011 2225 2232
30. K. Suzuki, B.P. Craddock, N. Okamoto, T. Kano, and R.T. Steigbigel Poly A-linked colorimetric microtiter plate assay for HIV reverse transcriptase J. Virol. Methods. 44 1993 189 198
31. Reverse Transcriptase Assay, Colorimetric kit, Roche Diagnostics GmbH, Roche. Applied Science, Sandhofer Strasse 116, D-68305 Mannheim, Germany.