Design, synthesis and anti-HIV evaluation of novel diarylnicotinamide derivatives (DANAs) targeting the entrance channel of the NNRTI binding pocket through structure-guided molecular hybridization

European Journal of Medicinal Chemistry

Volumn 87, Issue , 2014, Pages 52-62

  Liu, Zhaoqiang ^a   Chen, Wenmin ^a   Zhan, Peng ^a   De Clercq, Erik ^b   Pannecouque, Christophe ^b   Liu, Xinyong ^a  

^a SHANDONG UNIVERSITY   (China)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

DANAs; Drug design; Entrance channel; HIV 1; Molecular hybridization; NNRTIs

Indexed keywords

4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO] N (2 METHOXYETHYL)NICOTINAMIDE; 4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO] N (2,2 DIMETHOXYETHYL)NICOTINAMIDE; 4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO] N (CYCLOPROPYLMETHYL)NICOTINAMIDE; 4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO] N (PROP 2 YN 1 YL)NICOTINAMIDE; 4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO] N CYCLOPROPYLNICOTINAMIDE; 4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO] N PROPYLNICOTINAMIDE; 4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO] N [(TETRAHYDROFURAN 2 YL)METHYL]NICOTINAMIDE; 4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO] N [2 (DIMETHYLAMINO)ETHYL]NICOTINAMIDE; 4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO]NICOTINAMIDE; 4 (4 CYANO 2,6 DIMETHYLPHENOXY) N (2 CYANOETHYL) 6 [(4 CYANOPHENYL)AMINO]NICOTINAMIDE; 6 [(4 CYANOPHENYL)AMINO] 4 (MESITYLOXY) N (2 METHOXYETHYL)NICOTINAMIDE; 6 [(4 CYANOPHENYL)AMINO] 4 (MESITYLOXY) N (PROPYL 2 YN 1 YL)NICOTINAMIDE; 6 [(4 CYANOPHENYL)AMINO] 4 (MESITYLOXY) N PROPYLNICOTINAMIDE; 6 [(4 CYANOPHENYL)AMINO] 4 (MESITYLOXY) N [(TETRAHYDROFURAN 2 YL)METHYL]NICOTINAMIDE; 6 [(4 CYANOPHENYL)AMINO] 4 (MESITYLOXY)NICOTINAMIDE; 6 [(4 CYANOPHENYL)AMINO] N (2,2 DIMETHOXYETHYL) 4 (MESITYLOXY)NICOTINAMIDE; 6 [(4 CYANOPHENYL)AMINO] N (CYCLOPROPYLMETHYL) 4 (MESITYLOXY)NICOTINAMIDE; 6 [(4 CYANOPHENYL)AMINO] N CYCLOPROPYL 4 (MESITYLOXY)NICOTINAMIDE; 6 [(4 CYANOPHENYL)AMINO] N [2 (DIMETHYLAMINO)ETHYL] 4 (MESITYLOXY)NICOTINAMIDE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DELAVIRDINE; DIDANOSINE; EFAVIRENZ; N (2 CYANOETHYL) 6 [(4 CYANOPHENYL)AMINO] 4 (MESITYLOXY)NICOTINAMIDE; N ALLYL 4 (4 CYANO 2,6 DIMETHYLPHENOXY) 6 [(4 CYANOPHENYL)AMINO]NICOTINAMIDE; N ALLYL 6 [(4 CYANOPHENYL)AMINO] 4 (MESITYLOXY)NICOTINAMIDE; NEVIRAPINE; NICOTINAMIDE DERIVATIVE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; NICOTINAMIDE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG BINDING SITE; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; EC50; ENZYME INHIBITION; ENZYME INHIBITION ASSAY; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; IC50; MOLECULAR HYBRIDIZATION; MOLECULAR MODEL; NONHUMAN; STRUCTURE ACTIVITY RELATION; WILD TYPE; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; ENZYME ACTIVE SITE; ENZYMOLOGY; EVALUATION STUDY; HIV INFECTIONS; HUMAN; PROTEIN CONFORMATION; SYNTHESIS; TUMOR CELL CULTURE; VIROLOGY;

ANTI-HIV AGENTS; CATALYTIC DOMAIN; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; HIV INFECTIONS; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NIACINAMIDE; PROTEIN CONFORMATION; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED;

EID: 84907214176     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.09.054     Document Type: Article

References (26)

1. S. Martins, M.J. Ramos, P.A. Fernandes, The current status of the NNRTI family of antiretrovirals used in the HAART regime against HIV infection, Curr. Med. Chem. 15 (2008) 1083-1095
2. P. Zhan, X. Liu, Z. Li, C. Pannecouque, E. De Clercq, Design strategies of novel NNRTIs to overcome drug resistance, Curr. Med. Chem. 16 (2009) 3903-3917
3. P. Zhan, X. Chen, D. Li, Z. Fang, E. De Clercq, X. Liu, HIV-1 NNRTIs: structural diversity, pharmacophore similarity, and implications for drug design, Med. Res. Rev. 33 (2013) E1eE72
4. D. Li, P. Zhan, E. De Clercq, X. Liu, Strategies for the design of HIV-1 nonnucleoside reverse transcriptase inhibitors: lessons from the development of seven representative paradigms, J. Med. Chem. 55 (2012) 3595-3613
5. X. Chen, P. Zhan, D. Li, E. De Clercq, X. Liu, Recent advances in DAPYs and related analogues as HIV-1 NNRTIs, Curr. Med. Chem. 18 (2011) 359-376
6. T.M. Williams, T.M. Ciccarone, S.C. Mactough, C.S. Rooney, S.K. Balani, J.H. Condra, E.A. Emini, M.E. Goldman, W.J. Greenlee, L.R. Kauffman, J.A. O'Brien, V. V Sardana, W.A. Schleif, A.D. Theoharides, P.S. Anderson, 5-Chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase, J. Med. Chem. 36 (1993) 1291-1294
7. Z. Zhao, S.E. Wolkenberg, M. Lu, V. Munshi, G. Moyer, M. Feng, A.V. Carella, L.T. Ecto, L.J. Gabryelski, M.T. Lai, S.G. Prasad, Y. Yan, G.B. McGaughey, M.D. Miller, C.W. Lindsley, G.D. Hartman, J.P. Vaccaa, T.M. Williamsa, Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs), Bioorg. Med. Chem. Lett. 18 (2008) 554-559
8. G. La Regina, A. Coluccia, F. Piscitelli, A. Bergamini, A. Sinistro, A. Cavazza, G. Maga, A. Samuele, S. Zanoli, E. Novellino, M. Artico, R. Silvestri, Indolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: role of two halogen atoms at the indole ring in Developing new analogues with improved antiviral activity, J. Med. Chem. 50 (2007) 5034-5038
9. F. Piscitelli, A. Coluccia, A. Brancale, G. La Regina, A. Sansone, C. Giordano, J. Balzarini, G. Maga, S. Zanoli, A. Samuele, R. Cirilli, F. La Torre, A. Lavecchia, E. Novellino, R. Silvestri, Discovery of potent inhibitors of HIV-1 non-nucleoside wild type and resistant mutant strains reverse transcriptase and coxsackie B4 virus, J. Med. Chem. 52 (2009) 1922-1934
10. G. La Regina, A. Coluccia, A. Brancale, F. Piscitelli, V. Gatti, G. Maga, A. Samuele, C. Pannecouque, D. Schols, J. Balzarini, E. Novellino, R. Silvestri, Indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: new cyclic substituents at indole-2-carboxamide, J. Med. Chem. 54 (2011) 1587-1598
11. G. La Regina, A. Coluccia, A. Brancale, F. Piscitelli, V. Famiglini, S. Cosconati, G. Maga, A. Samuele, E. Gonzalez, B. Clotet, D. Schols, J.A. Este, E. Novellino, R. Silvestri, New nitrogen containing substituents at the indole-2-carboxamide yield high potent and broad spectrum indolylarylsulfone HIV-1 non-nucleoside reverse transcriptase inhibitors, J. Med. Chem. 55 (2012) 6634-6638
12. V. Famiglini, G. La Regina, A. Coluccia, S. Pelliccia, A. Brancale, G. Maga, E. Crespan, R. Badia, B. Clotet, J.A. Esté, R. Cirilli, E. Novellino, R. Silvestri, New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors, Eur. J. Med. Chem. 80 (2014) 101-111
13. E.B. Lansdon, K.M. Brendza, M. Hung, R. Wang, S. Mukund, D. Jin, G. Birkus, N. Kutty, X.H. Liu, Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design, J. Med. Chem. 53 (2010) 4295-4299
14. R. Ragno, M. Artico, G. De Martino, G. La Regina, A. Coluccia, A. Di Pasquali, R. Silvestri, Docking and 3-D QSAR studies on indolyl aryl sulfones. Binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N-(2-hydroxyethyl)carboxamide and N-(2-hydroxyethyl)carbohydrazide derivatives, J. Med. Chem. 48 (2005) 213-223
15. R. Ragno, A. Coluccia, G. La Regina, G. De Martino, F. Piscitelli, A. Lavecchia, E. Novellino, A. Bergamini, C. Ciaprini, A. Sinistro, G. Maga, E. Crespan, M. Artico, R. Silvestri, Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide, J. Med. Chem. 49 (2006) 3172-3184
16. S. Yang, C. Pannecouque, D. Daelemans, X. Ma, Y. Liu, F. Chen, E. De Clercq, Molecular design, synthesis and biological evaluation of BP-O-DAPY and ODAPY derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors, Eur. J. Med. Chem. 65 (2013) 134-143
17. X. Chen, X. Liu, Q. Meng, D. Wang, H. Liu, E. De Clercq, C. Pannecouque, J. Balzarini, X. Liu, Novel piperidinylamino-diarylpyrimidine derivatives with dual structural conformations as potent HIV-1 non-nucleoside reverse transcriptase inhibitors, Bioorg. Med. Chem. Lett. 23 (2013) 6593-6597
18. J.I. Levin, E. Turos, S.M. Weinreb, An alternative procedure for the aluminummediated conversion of esters to amides, Synth. Commun. 12 (13) (1982) 989-993
19. R. Pauwels, J. Balzarini, M. Baba, R. Snoeck, D. Schols, P. Herdewijn, J. Desmyter, E. De Clercq, Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds, J. Virol. Methods 20 (1988) 309-321
20. C. Pannecouque, D. Daelemans, E. De Clercq, Tetrazolium-based colorimetric assay for the detection of HIV replication inhibitors: revisited 20 years later, Nat. Protoc. 3 (2008) 427-434
21. P. Zhan, X. Liu, Z. Li, Z. Fang, Z. Li, D. Wang, C. Pannecouque, E. De Clercq, Novel 1,2,3-Thiadiazole derivatives as HIV-1 NNRTIs with improved potency: synthesis and preliminary SAR studies, Bioorg. Med. Chem. 17 (2009) 5920-5927
22. K. Suzuki, B.P. Craddock, N. Okamoto, T. Kano, R.T. Steigbigel, Poly A-linked colorimetric microtiter plate assay for HIV reverse transcriptase, J. Virol. Methods 44 (1993) 189-198
23. P. Zhan, X. Chen, X. Li, D. Li, Y. Tian, W. Chen, C. Pannecouque, E. De Clercq, X. Liu, Arylazolylthioacetanilide. Part 8: design, synthesis and biological evaluation of novel 2-(2-(2,4-dichlorophenyl)-2H-1,2,4-Triazol-3-ylthio)-Narylacetamides as potent HIV-1 inhibitors, Eur. J. Med. Chem. 46 (2011) 5039-5045
24. M. Popovic, M.G. Sarngadharan, E. Read, 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
25. F. Clavel, D. Guetard, F. Brun-Vezinet, S. Chamaret, M.A. Rey, M.O. Santos-Ferreira, A.G. Laurent, C. Dauguet, C. Katlama, C. Rouzioux, D. Klatzmann, J.L. Champalimaud, L. Montagnier, Isolation of a new human retrovirus from West African patients with AIDS, Science 233 (1986) 343-346
26. X. Li,W. Chen, Y. Tian, H. Liu, P. Zhan, E. De Clercq, C. Pannecouque, J. Balzarini, X. Liu, Discovery of novel diarylpyrimidines as potent HIVNNRTIs via a structureguided core-refining approach, Eur. J. Med. Chem. 80 (2014) 112-121