Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro

Journal of Virology

Volumn 78, Issue 16, 2004, Pages 8654-8662

  Maeda, Kenji ^a   Nakata, Hirotomo ^a   Koh, Yasuhiro ^a   Miyakawa, Toshikazu ^a   Ogata, Hiromi ^a   Takaoka, Yoshikazu ^b   Shibayama, Shiro ^b   Sagawa, Kenji ^b   Fukushima, Daikichi ^b   Moravek, Joseph ^d   Koyanagi, Yoshio ^c   Mitsuya, Hiroaki ^a,e  

^a KUMAMOTO UNIV SCHOOL OF MEDICINE   (Japan)

^b ONO PHARMACEUTICAL CO   (Japan)

^c TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^d Moravek Biochemicals Inc   (United States)

^e NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 BUT 2 YL 1 YL 3 (CYCLOHEXYLHYDROXYMETHYL) 9 (3,5 DIMETHYL 1 PHENYL 1H PYRAZOL 4 YLMETHYL) 1,4,6 TRIAZASPIRO[5.5]UNDECANE 2,5 DIONE; 4 [(4 BROMOPHENYL)(ETHOXYIMINO)METHYL] 1' [(2,4 DIMETHYL 3 PYRIDINYL)CARBONYL] 4' METHYL 1,4' BIPIPERIDINE; [4 [4 (1 BUTYL) 3 (CYCLOHEXYLHYDROXYMETHYL) 2,5 DIOXO 1,4,9 TRIAZASPIRO[5.5]UNDEC 9 YLMETHYL]PHENOXY]BENZOIC ACID; AK 530; APLAVIROC; BETA CHEMOKINE; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR5 INHIBITOR; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 45523; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; NELFINAVIR; PIPERAZINE DERIVATIVE; RANTES; SAQUINAVIR; SPIRODIKETOPIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG; ZIDOVUDINE;

ANIMAL CELL; ANTIVIRAL ACTIVITY; ARTICLE; BINDING AFFINITY; CHEMOTAXIS; CHO CELL; COMPETITIVE INHIBITION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG POTENCY; DRUG PROTEIN BINDING; EPITOPE MAPPING; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IC 50; IMMUNOMODULATION; IN VITRO STUDY; INTERNALIZATION; MULTIDRUG RESISTANCE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SECRETION; T LYMPHOCYTE ACTIVATION; VIRUS ISOLATION;

ANIMALS; ANTI-HIV AGENTS; CHEMOKINES, CC; CHEMOTAXIS, LEUKOCYTE; CHO CELLS; CRICETINAE; DRUG RESISTANCE, VIRAL; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HUMANS; LEUKOCYTES, MONONUCLEAR; MICROBIAL SENSITIVITY TESTS; PIPERAZINES; RANTES; RECEPTORS, CCR5; SPIRO COMPOUNDS;

EID: 3543144738     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.78.16.8654-8662.2004     Document Type: Article

References (36)

1. Baba, M., O. Nishimura, N. Kanzaki, M. Okamoto, H. Sawada, Y. Iizawa, M. Shiraishi, Y. Aramaki, K. Okonogi, Y. Ogawa, K. Meguro, and M. Fujino. 1999. A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. Acad. Sci. USA 96:5698-5703.
2. Dean, M., M. Carrington, C. Winkler, G. A. Huttley, M. W. Smith, R. Allikmets, J. J. Goedert, S. P. Buchbinder, E. Vittinghoff, E. Gomperts, S. Donfield, D. Vlahov, R. Kaslow, A. Saah, C. Rinaldo, R. Detels, and S. J. O'Brien. 1996. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 273:1856-1862.
3. Dragic, T., A. Trkola, D. A. Thompson, E. G. Cormier, F. A. Kajumo, E. Maxwell, S. W. Lin, W. Ying, S. O. Smith, T. P. Sakmar, and J. P. Moore. 2000. A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc. Natl. Acad. Sci. USA 97:5639-5644.
4. Evans, E. A. 1974. Catalytic exchange in solution, p. 271-317. In Tritium and its compounds. Wiley and Sons, New York, N.Y.
5. Fauci, A. S. 2003. HIV and AIDS: 20 years of science. Nat. Med. 9:839-843.
6. + T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat. Med. 5:512-517.
7. Fiscbereder, M., B. Luckow, B. Hocher, R. P. Wuthrich, U. Rothenpieler, H. Schneeberger, U. Panzer, R. A. Stahl, I. A. Hauser, K. Budde, H. Neumayer, B. K. Kramer, W. Land, and D. Schlondorff.. 2001. CC chemokine receptor 5 and renal-transplant survival. Lancet 357:1758-1761.
8. Gartner, S., P. Markovits, D. M. Markovitz, M. H. Kaplan, R. C. Gallo, and M. Popovic. 1986. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215-219.
9. Glas, J., H. P. Torok, C. Simperl, A. Konig, K. Martin, F. Schmidt, M. Schaefer, U. Schiemann, and C. Folwaczny. 2003. The Delta 32 mutation of the chemokine-receptor 5 gene neither is correlated with chronic hepatitis C nor does it predict response to therapy with interferon alpha and ribavirin. Clin. Immunol. 108:46-50.
10. Gribble, G. W. 1975. Reactions of sodium borohydride in acidic media. Selective reduction of aldehydes with sodium triacetoborohydride. JCS Chem. Comm. 1975:535-541.
11. Kavlick, M. F., and H. Mitsuya. 2001. The emergence of drug-resistant human immunodeficiency virus type 1 variants and its impact on antiretroviral therapy of human immunodeficiency virus type 1 infection, p. 279-312. In E. de Clerq (ed.), The art of antiretroviral therapy. American Society for Microbiology, Washington, D.C.
12. Koh, Y., H. Nakata, K. Maeda, H. Ogata, G. Bilcer, T. Devasamudram, J. F. Kincaid, P. Boross, Y. F. Wang, Y. Tie, P. Volarath, L. Gaddis, R. W. Harrison, I. T. Weber, A. K. Ghosh, and H. Mitsuya. 2003. Novel bis- tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. Antimicrob. Agents Chemother. 47:3123-3129.
13. Koyanagi, Y., W. A. O'Brien, J. Q. Zhao, D. W. Golde, J. C. Gasson, and I. S. Chen. 1988. Cytokines after production of HIV-1 from primary mononuclear phagocytes. Science 241:1673-1675.
14. Lee, B., M. Sharron, C. Blanpain, B. J. Doranz, J. Vakili, P. Setoh, E. Berg, G. Liu, H. R. Guy, S. R. Durell, M. Parmentier, C. N. Chang, K. Price, M. Tsang, and R. W. Doms. 1999. Epitope mapping of CCR5 reveals multiple conformational states and distinct but overlapping structures involved in chemokine and coreceptor function. J. Biol. Chem. 274:9617-9626.
15. Liu, R., W. A. Paxton, S. Choe, D. Ceradini, S. R. Martin, R. Horuk, M. E. MacDonald, H. Stuhlmann, R. A. Koup, and N. R. Landau. 1996. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86:367-377.
16. + T-cell clone (PM1): failure to downregulate CD4 and to interfere with cell-line-tropic HIV-1. J. Virol. 69:3712-3720.
17. Maeda, K., K. Yoshimura, S. Shibayama, H. Habashita, H. Tada, K. Sagawa, T. Miyakawa, M. Aoki, D. Fukushima, and H. Mitsuya. 2001. Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5. J. Biol. Chem. 276:35194-35200.
18. Maeda, Y., M. Foda, S. Matsushita, and S. Harada. 2000. Involvement of both the V2 and V3 regions of the CCR5-tropic human immunodeficiency virus type 1 envelope in reduced sensitivity to macrophage inflammatory protein 1alpha. J. Virol. 74:1787-1793.
19. Marozsan, A. J., V. S. Torre, M. Johnson, S. C. Ball, J. V. Cross, D. J. Templeton, M. E. Quinones-Mateu, R. E. Offord, and E. J. Arts. 2001. Mechanisms involved in stimulation of human immunodeficiency virus type 1 replication by aminooxypentane RANTES. J. Virol. 75:8624-8638.
20. Mitsuya, H., and J. Erickson. 1999. Discovery and development of antiretroviral therapeutics for HIV infection, p. 751-780. In T. C. Merigan, J. G. Bartlet, and D. Bolognesi (ed.), Textbook of AIDS medicine. Williams & Wilkins, Baltimore, Md.
21. Miyakawa, T., K. Obaru, K. Maeda, S. Harada, and H. Mitsuya. 2002. Identification of amino acid residues critical for LD78beta, a variant of human macrophage inflammatory protein-1alpha, binding to CCR5 and inhibition of R5 human immunodeficiency virus type 1 replication. J. Biol. Chem. 277:4649-4655.
22. Moriuchi, H., M. Moriuchi, and A. S. Fauci. 1998. Factors secreted by human T lymphotropic virus type 1 (HTLV-1)-infected cells can enhance or inhibit replication of HIV-1 in HTLV-1-uninfected cells: implications for in vivo coinfection with HTLV-1 and HIV-1. J. Exp. Med. 187:1689-1697.
23. O'Brien, S. J., and J. P. Moore. 2000. The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS. Immunol. Rev. 177:99-111.
24. Olson, W. C., G. E. Rabut, K. A. Nagashima, D. N. Tran, D. J. Anselma, S. P. Monard, J. P. Segal, D. A. Thompson, F. Kajumo, Y. Guo, J. P. Moore, P. J. Maddon, and T. Dragic. 1999. Differential inhibition of human immunodeficiency virus type 1 fusion, gp120 binding, and CC-chemokine activity by monoclonal antibodies to CCR5. J. Virol. 73:4145-4155.
25. Samson, M., F. Libert, B. J. Doranz, J. Rucker, C. Liesnard, C. M. Farber, S. Saragosti, C. Lapoumeroulie, J. Cognaux, C. Forceille, G. Muyldermans, C. Verhofstede, G. Burtonboy, M. Georges, T. Imai, S. Rana, Y. Yi, R. J. Smyth, R. G. Collman, R. W. Doms, G. Vassart, and M. Parmentier. 1996. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382:722-725.
26. Shirasaka, T., M. F. Kavlick, T. Ueno, W. Y. Gao, E. Kojima, M. L. Alcaide, S. Chokekijchai, B. M. Roy, E. Arnold, R. Yarchoan, and H. Mitsuya. 1995. Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc. Natl. Acad. Sci. USA 92:2398-2402.
27. + T cells. Nat. Med. 9:727-728.
28. Strizki, J. M., S. Xu, N. E. Wagner, L. Wojcik, J. Liu, Y. Hou, M. Endres, A. Palani, S. Shapiro, J. W. Clader, W. J. Greenlee, J. R. Tagat, S. McCombie, K. Cox, A. B. Fawzi, C. C. Chou, C. Pugliese Sivo, L. Davies, M. E. Moreno, D. D. Ho, A. Trkola, C. A. Stoddart, J. P. Moore, G. R. Reyes, and B. M. Baroudy. 2001. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc. Natl. Acad. Sci. USA 98:12718-12723.
29. Thelen, M. 2001. Dancing to the tune of chemokines. Nat. Immunol. 2:129-134.
30. Tsamis, F., S. Gavrilov, F. Kajumo, C. Seibert, S. Kuhmann, T. Ketas, A. Trkola, A. Palani, J. W. Clader, J. R. Tagat, S. McCombie, B. Baroudy, J. P. Moore, T. P. Sakmar, and T. Dragic. 2003. Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH 351125 and SCH-350581 inhibit human immunodeficiency virus type 1 entry. J. Virol. 77:5201-5208.
31. Trkola, A., S. E. Kuhmann, J. M. Strizki, E. Maxwell, T. Ketas, T. Morgan, P. Pugach, S. Xu, L. Wojcik, J. Tagat, A. Palani, S. Shapiro, J. W. Clader, S. McCombie, G. R. Reyes, B. M. Baroudy, and J. P. Moore. 2002. HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc. Natl. Acad. Sci. USA 99:395-400.
32. Veazey, R. S., P. J. Klasse, T. J. Ketas, J. D. Reeves, M. Piatak, Jr., K. Kunstman, S. E. Kuhmann, P. A. Marx, J. D. Lifson, J. Dufour, M. Mefford, I. Pandrea, S. M. Wolinsky, R. W. Doms, J. A. DeMartino, S. J. Siciliano, K. Lyons, M. S. Springer, and J. P. Moore. 2003. Use of a small molecule CCR5 inhibitor in macaques to treat simian immunodeficiency virus infection or prevent simian-human immunodeficiency virus infection. J. Exp. Med. 198:1551-1562.
33. Vodicka, M. A., W. C. Goh, L. I. Wu, M. E. Rogel, S. R. Bartz, V. L. Schweickart, C. J. Raport, and M. Emerman. 1997. Indicator cell lines for detection of primary strains of human and simian immunodeficiency viruses. Virology 233:193-198.
34. Westervelt, P., H. E. Gendelman, and L. Ratner. 1991. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc. Natl. Acad. Sci. USA 88:3097-3101.
35. Woitas, R. P., G. Ahlenstiel, A. Iwan, J. K. Rockstroh, H. H. Brackmann, B. Kupfer, B. Matz, R. Offergeld, T. Sauerbrucb, and U. Spengler. 2002. Frequency of the HIV-protective CC chemokine receptor 5-Delta32/Delta32 genotype is increased in hepatitis C. Gastroenterology 122:1721-1728.
36. Yoshimura, K., R. Kato, K. Yusa, M. F. Kavlick, V. Maroun, A. Nguyen, T. Mimoto, T. Ueno, M. Shintani, J. Falloon, H. Masur, H. Hayashi, J. Erickson, and H. Mitsuya. 1999. JE-2147: a dipeptide protease inhibitor (PI) that potently inhibits multi-PI-resistant HIV-1. Proc. Natl. Acad. Sci. USA 96:8675-8680.