New nitrogen containing substituents at the indole-2-carboxamide yield high potent and broad spectrum indolylarylsulfone HIV-1 non-nucleoside reverse transcriptase inhibitors

Journal of Medicinal Chemistry

Volumn 55, Issue 14, 2012, Pages 6634-6638

  La Regina, Giuseppe ^a   Coluccia, Antonio ^a   Brancale, Andrea ^b,c   Piscitelli, Francesco ^a   Famiglini, Valeria ^a   Cosconati, Sandro ^g   Maga, Giovanni ^c   Samuele, Alberta ^c   Gonzalez, Emmanuel ^d   Clotet, Bonaventura ^d   Schols, Dominique ^e   Esté, José A ^d   Novellino, Ettore ^f   Silvestri, Romano ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b CARDIFF UNIVERSITY   (United Kingdom)

^c CNR   (Italy)

^d HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

^e REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^f UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^g SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

5 CHLORO N (3 CYANOPHENYL) 3 [(3,5 DIMETHYLPHENYL)SULFONYL] 1H INDOLE 2 CARBOXAMIDE; AMIDE; DELAVIRDINE; EFAVIRENZ; INDOLE 2 CARBOXAMIDE; INDOLE DERIVATIVE; MARAVIROC; NEVIRAPINE; NITROGEN DERIVATIVE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; PLERIXAFOR; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE; RNA DIRECTED DNA POLYMERASE; SULFONE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CLADISTICS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROPHOBICITY; MOLECULAR DOCKING; MOLECULAR INTERACTION; MULTIDRUG RESISTANCE; MUTATION; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; STRUCTURE ACTIVITY RELATION; VIRUS STRAIN;

CELL LINE; HIV REVERSE TRANSCRIPTASE; HIV-1; INDOLES; MUTATION; NITROGEN; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES;

EID: 84864247649     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300477h     Document Type: Article

References (18)

1. Progress Report 2011: Global HIV/AIDS Response; World Health Organization: Geneva, 2011.
2. Este, J. A.; Cihlar, T. Current status and challenges of antiretroviral research and therapy Antiviral Res. 2010, 85, 25-33
3. Menéndez-Arias, L. Molecular basis of human immunodeficiency virus drug resistance: an update Antiviral Res. 2010, 85, 210-231
4. Cortez, K. J.; Maldarelli, F. Clinical management of HIV drug resistance Viruses 2011, 3, 347-378
5. Howkins, T. Understanding and managing the adverse effects of antiretroviral therapy Antiviral Res. 2010, 85, 201-209
6. de Béthune, M.-P. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery, development, and use in the treatment of HIV-1 infection: a review over the last 20 years (1989-2009) Antiviral Res. 2010, 85, 75-90
7. Sweeney, Z. K.; Klumpp, K. Improving non-nucleoside reverse transcriptase inhibitors for first-line treatment of HIV infection: the development pipeline and recent clinical data Curr. Opin. Drug Discovery Dev. 2008, 11, 458-470
8. Haubrich, R.; Gubernick, S.; Yasothan, U.; Kirkpatrick, P. Etravirine Nature Rev. Drug Discovery 2008, 7, 287-288
9. Drugs@FDA. FDA approved drug products; http://www.accessdata.fda.gov/ scripts/ cder/drugsatfda/index.cfm (Accessed February 20, 2012).
10. Silvestri, R.; De Martino, G.; La Regina, G.; Artico, M.; Massa, S.; Vargiu, L.; Mura, M.; Loi, A. G.; Marceddu, T.; La Colla, P. Novel indolyl aryl sulfones active against HIV-1 carrying NNRTI resistance mutations: synthesis and SAR studies J. Med. Chem. 2003, 46, 2482-2493
11. Silvestri, R.; Artico, M.; De Martino, G.; La Regina, G.; Loddo, R.; La Colla, M.; La Colla, P. Simple, short peptide derivatives of a sulfonylindolecarboxamide (L-737,126) active in vitro against HIV-1 wild-type and variants carrying non-nucleoside reverse transcriptase inhibitor resistance mutations J. Med. Chem. 2004, 47, 3892-3896
12. Piscitelli, F.; Coluccia, A.; Brancale, A.; La Regina, G.; Sansone, A.; Giordano, C.; Balzarini, J.; Maga, G.; Zanoli, S.; Samuele, A.; Cirilli, R.; La Torre, F.; Lavecchia, A.; Novellino, E.; Silvestri, R. Indolylarylsulfones bearing natural and unnatural amino acids. Discovery of potent inhibitors of HIV-1 non-nucleoside wild type and resistant mutant strains reverse transcriptase and Coxsackie B4 virus J. Med. Chem. 2009, 52, 1922-1934
13. Ragno, R.; Artico, M.; De Martino, G.; La Regina, G.; Coluccia, A.; Di Pasquali, A.; Silvestri, R. Docking and 3-D QSAR studies on indolyl aryl sulfones (IASs). binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N -(2-hydroxyethyl) carboxyamide and N -(2-hydroxyethyl)carboxyhydrazide derivatives J. Med. Chem. 2005, 48, 213-223
14. Ragno, R.; Coluccia, A.; La Regina, G.; De Martino, G.; Piscitelli, F.; Lavecchia, A.; Novellino, E.; Bergamini, A.; Ciaprini, C.; Sinistro, A.; Maga, G.; Crespan, E.; Artico, M.; Silvestri, R. Design, molecular modeling, synthesis and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide J. Med. Chem. 2006, 49, 3172-3184
15. La Regina, G.; Coluccia, A.; Silvestri, R. Looking for an active conformation of the future HIV-1 non-nucleoside reverse transcriptase inhibitors Antiviral Chem. Chemother. 2010, 20, 231-237
16. La Regina, R.; Coluccia, A.; Brancale, A.; Piscitelli, F.; Gatti, V.; Maga, G.; Samuele, A.; Pannecouque, C.; Schols, D.; Balzarini, J.; Novellino, E.; Silvestri, R. Indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors. New cyclic substituents at the indole-2-carboxamide J. Med. Chem. 2011, 54, 1587-1598
17. Corbett, J. W.; Rodgers, J. D. Discovery of second generation of quinazoline non-nucleoside reverse transcriptase inhibitors of HIV-1 Prog. Med. Chem. 2002, 40, 63-105
18. Manetti, F.; Este, J. A.; Clotet-Codina, I.; Armand-Ugon, M.; Maga, G.; Crespan, E.; Cancio, R.; Mugnaini, C.; Bernardini, C.; Togninelli, A.; Carmi, C.; Alongi, M.; Petricci, E.; Massa, S.; Corelli, F.; Botta, M. Parallel solution-phase and microwave-assisted synthesis of new S-DABO derivatives endowed with subnanomolar anti-HIV-1 activity J. Med. Chem. 2005, 48, 8000-8008