Non-nucleoside HIV-1 reverse transcriptase inhibitors: Synthesis and biological evaluation of novel quinoxalinylethylpyridylthioureas as potent antiviral agents

Antiviral Chemistry and Chemotherapy

Volumn 11, Issue 2, 2000, Pages 141-155

  Campiani, G ^a   Fabbrini, M ^b   Morelli, E ^b   Nacci, V ^b   Greco, G ^c   Novellino, E ^c   Maga, G ^d   Spadari, S ^d   Bergamini, A ^e   Faggioli, E ^e   Uccella, I ^e   Bolacchi, F ^e   Marini, S ^e   Coletta, M ^e   Fracasso, C ^f   Caccia, S ^f  

^a UNIVERSITY OF SALERNO   (Italy)

^b UNIVERSITY OF SIENA   (Italy)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^d CNR   (Italy)

^e UNIVERSITY OF ROME TOR VERGATA   (Italy)

^f MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

Author keywords

HIV; Non nucleoside HIV 1 RT inhibitors; QXPTs; Thioureas

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; NEVIRAPINE; RNA DIRECTED DNA POLYMERASE INHIBITOR; ZIDOVUDINE;

AMINO ACID SUBSTITUTION; ANIMAL EXPERIMENT; ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG POTENTIATION; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MACROPHAGE; MALE; MONOCYTE; MOUSE; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

EID: 17144438394     PISSN: 09563202     EISSN: None     Source Type: Journal    
DOI: 10.1177/095632020001100206     Document Type: Article

References (42)

1. Ahgren C, Backro K, Bell FW, Cantrell S, Clemens M, Colacino JM, Deter JB, Engelhardt JA, Ogberg M, Jaskunas SR, Jonhansson NG, Jordan CL, Kasher JS, Kinnik MD, Lind P, Lopez C, Morin Jr JM, Muesing MA, Noreen R, Oberg B, Pagget CJ, Palkowitz JA, Parrish CA, Pranc P, Rippy MK, Rydergard C, Sahlberg C, Swanson S, Ternansky RJ, Unge T, Vasileff RT, Wrang L, West SJ, Zhang H & Zhou X-X (1995) The PETT series, a new class of potent non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. Antimicrobial Agents and Chemotherapy 39:1329-1335.
2. Akira M & Watanabe T (1975) Japanese Patent 74 27,877, 22 July 1974, Appl. 70 129,461, 30 December 1970; Chemical Abstract 82:156398q.
3. Barre'-Sinoussi F, Chermann JC, Rey F, Nugeyre M, Chamaret S, Gruest J, Dauguet C, Axlar-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W & Montagner L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome. Science 220:868-871.
4. Bell FW, Cantrell AS, Hogberg M, Jaskunas R, Johansson NG, Jordan CL, Kinnick MD, Lind P, Morin Jr JM, Noreen R, Oberg B, Palkovitz JA, Parrish CA, Pranc P, Sahlberg C, Ternansky RJ, Vasileff RT, Wrang L, West SJ, Zhang H & Zhou X-X (1995) Phenetylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs. Journal of Medicinal Chemistry 38:4929-4936.
5. Bergamini A, Perno CF & Capozzi M (1992) A tetrazolium-based colorimetric assay for quantification of HIV-1-induced cytopathogenicity in monocyte-macrophages exposed to macrophage-colony stimulating factor. Journal of Virological Methods 40:275-286.
6. Campiani G, Nacci V, Fiorini I, De Filippis MP, Garofalo A, Greco G, Novellino E, Altamura S & Di Renzo L (1996) Pyrrolobenzothiazepinones and pyrrolobenzoxazepinones: novel and specific non-nucleoside HIV-1 reverse transcriptase inhibitors with antiviral activity. Journal of Medicinal Chemistry 39:2672-2680.
7. Campiani G, Sun L-Q, Kozikowski AP, Aagaard P & McKinney M (1993) A palladium-catalyzed route to huperzine A and its analogues and their acetylcholinesterase activity. Journal of Organic Chemistry 58: 7660-7669.
8. Campiani G, Cappelli A, Nacci V, Anzini M, Vomero S, Hamon M, Cagnotto A, Fracasso C, Uboldi C, Caccia S, Consolo S & Mennini T (1997) Novel and highly potent 5-HT3 receptor agonists based on a pyrroloquinoxaline structure. Journal of Medicinal Chemistry 40:3670-3678.
9. Campiani G, Morelli E, Fabbrini M, Nacci V, Greco G, Novellino E, Ramunno A, Maga G, Spadari S, Caliendo G, Bergamini A, Faggioli E, Uccella I, Bolacchi F, Marini S, Coletta M, Nacca A & Caccia S (1999a) Pyrrolobenzoxazepinone derivatives as non-nucleoside HIV-1 RT inhibitors: further structure-activity relationship studies and identification of more potent broad-spectrum HIV-1 RT inhibitors with antiviral activity. Journal of Medicinal Chemistry 42:4462-4470.
10. 3 receptor agonists. Synthesis, further structure-activity relationships, and biological studies. Journal of Medicinal Chemistry 42:4362-4379.
11. Cantrell SA, Engelhardt P, Hogberg M, Jaskunas SR, Johansson NG, Jordan CL, Kangasmetsa J, Kinnik MD, Lind P, Morin Jr JM, Muesing Jr JM, Noreen R, Oberg B, Pranc P, Sahlberg C, Ternansky RJ, Vasileff RT, Wrang L, West SJ & Zhang H (1996) Phenetylthiazolethiourea (PETT) compounds, as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs. Journal of Medicinal Chemistry 39:4261-4274.
12. Carboni B, Vaultier M & Carrie R (1987) Etude de la chinioselective de la reaction des dichloroborane avec les azides fonctionnels: une synthese efficace d'amines secondaries fonctionnalisees. Tetrahedron 43:1799-1810.
13. Chou TC (1976) Derivation and properties of Michaelis-Menton type and Hill type equations for reference ligands. Journal of Theoretical Biology 59:253-276.
14. Chou TC & Talalay I (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Advances in Enzyme Regulation 22:27-55.
15. Cretton EM, Xie M-Y, Bevan RJ, Goudgaon NM, Schinazi RF & Sommadossi J-P (1991) Catabolism of 3′-azido-3′-deoxythymidine in hepatocvtes and liver microsomes with evidence of formation of 3′-amino-3′-deoxythymidine, a highly toxic catabolite for human bone marrow cells. Molecular Pharmacology 39:258-266.
16. D'Atri S, Tentori L, Fuggetta MP, Marini S & Bonmassar E (1986) A miniaturized cell-mediated cytotoxicity assay with human effector mononuclear cells. International Journal of Tissue Reaction 7:383-390.
17. Davey DD, Erhardt PW, Cantoe EH, Greenberg SS, Ingebretsen WR & Wiggins J (1991) Novel compounds possessing potent cAMP and cGMP phosphodiesterase inhibitory activity. Synthesis and cardiovascular effects of a series of imidazo[1,2-a]quinoxalinones and imidazo[1,5-a]quinoxalinones, and their aza analogues. Journal of Medicinal Chemistry 34:2671-2677.
18. De Clercq E (1990) Targets and strategies for the antiviral chemotherapy of AIDS. Trends in Pharmacological Sciences 11:198-205.
19. De Clercq E (1995) Toward improved anti-HIV chemotherapy: therapeutic strategies for intervention with HIV infections. Journal of Medicinal Chemistry 38:2491-2517.
20. Gao WJ, Agbaria R, Driscoll JS & Mitsuya H (1994) Divergent anti-human immunodeficiency virus activity and anabolic phosphorylation of 2′,3′-dideoxynucleoside analogues in resting and activated human cells. Journal of Biological Chemistry 269:12633-12638.
21. Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC & Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:1533-1544.
22. Goldman ME, Nunberg JH, O'Brien JA, Quintero JC, Schleif WA, Freund KF, Gaul SL, Saari WS, Wai JS, Hoffman JM, Anderson PS, Hupe DJ, Emini, EA & Stern AM (1991) Pyridone derivatives: specific human immunodeficiency virus type-1 reverse transcriptase inhibitors with antiviral activity. Proceedings of the National Academy of Sciences, USA 88:6863-6867.
23. Hargrave KD, Proudfoot JR, Grozinger KG, Cullen E, Kapadia SR, Patel UR, Fuchs VU, Mauldin SC, Vitous J, Behnke ML, Klunder JM, Pal K, Skiles JW, McNeil DW, Rose JM, Chow GC, Skoog MT, Wu JC, Schmidt G, Engel WW, Eberlein WG, Saboe TD, Campbell SJ, Rosenthal AS & Adams J (1991) Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Tricyclic pyridobenzo-and dipyridodiazepinones. Journal of Medicinal Chemistry 34:2231-2241.
24. Karber G (1931) Beitrag zur kollektiven behandlung pharmakologischer reihenversuche. Archiv für Experimental Pharmakologie 162:480-483.
25. Kumar R, Wang L, Wiebe LI & Knaus EE (1994) Synthesis and antiviral (HIV-1, HBV) activities of 5-halo-6-methoxy(or azido)-5,6-dihydro-3′-fluoro-3′-deoxythymidine diastereomers. Potential prodrugs to 3′-fluoro-3′-deoxythymidine. Journal of Medicinal Chemistry 37:3554-3560.
26. Levin VA (1980) Relationship of octanol/water partition coefficient and molecular weight to rat brain permeability. Journal of Medicinal Chemistry 23:682.
27. Maga G, Amacker M, Ruel N, Hubsher U & Spadari S (1997) Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions. Journal of Molecular Biology 274:738-747.
28. Makino K & Yoshioka H (1987) Facile synthesis and herbicidal activities of novel fluoroquinoxalines. Heterocycles 26:1215-1220.
29. McQuaid LA, Smith E, South K, Mitch CH, Schoepp D, True RA, Calligaro DO & O'Malley PJ (1992) Synthesis and excitatory aminoacids pharmacology of a series of heterocyclic-fused quinoxalinones and quinazolinones. Journal of Medicinal Chemistry 35:3319-3324.
30. Pauwels R, Balzarini J & Baba M (1988) Rapid and automated tetrazolium based colorimetric assay for the detection of anti-HIV compounds. Journal of Virological Methods 20:309-321.
31. Pauwels R, Andries K, Desmyter J, Schols D, Kukla MJ, Breslin HJ, Raeymaeckers A, Van Gelder J, Woestenborghs R, Heykants J, Schellekens K, Janssen MAC, De Clercq E & Janssen PAJ (1990) Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature 343:470-474.
32. Perno CF, Yarchoan R & Cooney DA (1988) Inhibition of human immunodeficiency virus (HIV-1/HTLV-III-Ba-1) replication in fresh and cultured human peripheral blood monocytes/macrophages by azidothymidine and related 2′,3′-dideoxynucleosides. Journal of Experimental Medicine 168:1111-1125.
33. Popovic M, Sarngadharen MG, Read E & Gallo RC (1984) Detection, isolation and continues production of cytopathic retrovirus (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497-500.
34. Portegies P (1995) HIV-1, the brain, and combination therapy. Lancet 346:1244-1245.
35. 3 receptors. 2. Synthesis and biological evaluation of piperazinopyridopyrrolopyrazines, piperazinopyrroloquinoxalines, and piperazinopyridopyrroloquinoxalines. Journal of Medicinal Chemistry 40:1808-1819.
36. Reddy PY, Kondo S, Toru T & Ueno Y (1997) Lewis acid and hexamethyldisilazane-promoted efficient synthesis of N-alkyl and N-arylimide derivatives. Journal of Organic Chemistry 62:2652-2654.
37. Resnick L, Berger JR, Shapshak P & Tourtellotte WW (1988) Early penetration of the blood-brain barrier by HIV. Neurology 38:9-14.
38. Richman DD (1993) Resistance of clinical isolates of human immunodeficiency virus to antiretroviral agents. Antimicrobial Agents and Chemotherapy 37:1207-1221.
39. Sandstrom E & Oberg B (1993) Antiviral therapy in human immunodeficiency virus infections. Drugs 45:488-508.
40. Sodroski JG, Rosen CA & Haseltine WA (1984) Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science 225:381-385.
41. Terasaki T & Pardridge WM (1988) Restricted transport of 3′-azido-3′-deoxythymidine and dideoxynucleosides through the blood-brain barrier. Journal of Infectious Diseases 158:630-632.
42. Weislow OW, Kiser R, Fine B, Bader J, Shoemaker R & Boyd MR (1989) New soluble-formazan assay for HIV-1 cytopathic effects: application of high-flux screening of synthetic and natural products for AIDS-antiviral activity. Journal of the National Cancer Institute 81:577-586.