Design and synthesis of new potent C2-symmetric HIV-1 protease inhibitors. Use of L-mannaric acid as a peptidomimetic scaffold

Journal of Medicinal Chemistry

Volumn 41, Issue 20, 1998, Pages 3782-3792

  Alterman, Mathias ^a   Björsne, Magnus ^b   Mühlman, Anna ^b   Classon, Björn ^b   Kvarnström, Ingemar ^c   Danielson, Helena ^a   Markgren, Per Olof ^a   Nillroth, Ulrika ^a   Unge, Torsten ^a   Hallberg, Anders ^a   Samuelsson, Bertil ^b,d  

^a UPPSALA UNIVERSITY   (Sweden)

^b STOCKHOLM UNIVERSITY   (Sweden)

^c LINKÖPING UNIVERSITY   (Sweden)

^d ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; INDINAVIR; MANNARIC ACID; N1,N6 DI(HYDROXY 1 INDANYL) 2,5 DI(BENZYLOXY) 3,4 DIHYDROXYHEXANEDIAMIDE; N1,N6 DI[2 METHYL 1 (METHOXYCARBONYL)PROPYL] 2,5 DI(BENZYLOXY) 3,4 DIHYDROXYHEXANEDIAMIDE; N1,N6 DI[2 METHYL 1 (METHYLCARBAMOYL)BUTYL] 2,5 DI(BENZYLOXY) 3,4 DIHYDROXYHEXANEDIAMIDE; N1,N6 DI[2 METHYL 1 (METHYLCARBAMOYL)PROPYL] 2,5 DI(BENZYLOXY) 3,4 DIHYDROXYHEXANEDIAMIDE; PROTEINASE; PROTEINASE INHIBITOR; RITONAVIR; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG CONFORMATION; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROGEN BOND; MOLECULAR MODEL; PROTEINASE INHIBITION; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

EID: 14444280615     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970777b     Document Type: Article

References (53)

1. (a) Barré-Sinoussi, F.; Chermann, J. C.; Rey, F.; Nugeyre, M. T., Chamaret, S.; Gruest, J.; Dauguet, C.; Axler-Blin, C.; Vézinet-Brun, F.; Rouzioux, C.; Rozenbaum, W.; Montagnier, L. Isolation of a T-lymphotropic retro virus from a patient at risk for acquired immune deficiency syndrome. Science 1983, 220, 868-871.
2. (b) Gallo, R. C.; Sarin, P. S.; Gelman, E. P.; Robert-Guroff, M.; Richardson, E.; Kalyanaraman, V. S.; Mann, D.; Sidhu, G. D.; Stahl, R. E.; Zolla-Pazner, S.; Leibowitch, J.; Popovic, M. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science 1983, 220, 865-867.
3. (c) Clavel, F.; Guétard, D.; Brun-Vézinet, F.; Chamaret, S.; Rey, M.-A.; Santos-Ferreira, M. O.; Laurent, A. G.; Dauguet, C.; Katlama, C.; Rouzioux, C.; Klatzmann, D.; Champalimaud, J. L.; Montagnier, L. Isolation of a new human retrovirus from west Africa patients with AIDS. Science 1986, 233, 343-346.
4. (a) McQuade, T. J.; Tomaselli, A. G.; Liu, L.; Karacostas, V.; Moss, B.; Sawyer, T. K.; Heinrikson, R. L.; Tarpley, W. G. A synthetic HIV-1 protease inhibitor with antiviral activity arrests HIV-like particle maturation. Science 1990, 247, 454-456.
5. (b) Seelmeier, S.; Schmidt, H.; Turk, V.; von der Helm, K. Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 6612-6616.
6. (a) Kohl, N. E.; Emini, E. A.; Schleif, W. A.; Davis, L. J.; Heimbach, J. C.; Dixon, R. A. F.; Scolnick, E. M.; Sigal, I. S. Active human immunodeficiency virus protease is required for viral infectivity. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 4686-4690.
7. (b) Gottlinger, H. G.; Sodroski, J. G.; Haseltine, W. A. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 5781-5785.
8. (c) Peng, C.; Ho, B. K.; Chang, T. W.; Chang, N. T. Role of human immunodeficiency virus type 1-specific protease in core protein maturation and viral infectivity. J. Virol. 1989, 63, 2550-2556.
9. Sham, H. L.; Chen, X. HIV protease inhibitors in early development. Exp. Opin. Invest. Drugs 1996, 5, 977-983.
10. (a) Naesens, L.; De Clercq, E. Present status of HIV protease inhibitors in the control of HIV infection. Exp. Opin. Invest. Drugs 1996, 5, 153.
11. (b) De Clercq, E. Toward improved anti-HIV chemotherapy: Therapeutic strategies for intervention with HIV infections. J. Med. Chem. 1995, 38, 2491-2517.
12. (c) Redshaw, S. Inhibitors of HIV proteinase. Exp. Opin. Invest. Drugs 1994, 3, 273-286.
13. (d) Wlodawer, A.; Erickson, J. Structure-based inhibitors of HIV-1 protease. W. Annu. Rev. Biochem. 1993, 62, 543-585.
14. (e) Meek, T. D. Inhibitors of HIV-1 protease. J. Enzyme Inhib. 1992, 6, 65-98.
15. (f) Norbeck, D. W.; Kempf, D. HIV protease inhibitors. J. Annu. Rep. Med. Chem. 1991, 26, 141-150.
16. (g) Huff, J. R. HIV Protease: A novel chemotherapeutic target for AIDS. J. Med. Chem. 1991, 34, 2305-2314.
17. (h) Kempf, D. J.; Sham, H. L. HIV Protease inhibitors. Curr. Pharm. Design 1996, 2, 225-246.
18. Greer, J.; Erickson, J. W.; Baldwin, J. J.; Varney, M. D. Application of the three-dimensional structures of protein target molecules in structure-based drug design. J. Med. Chem. 1994, 37, 1035-1054.
19. 2 symmetric potential inhibitors of HIV-1 protease from D-mannitol. J. Carbohydr. Chem. 1996, 15, 555-569.
20. Zuccarello, G.; Bouzide, A.; Kvarnström, I.; Niklasson, G.; Svensson, S. C. T.; Brisander, M.; Classon, B.; Danielson, U. H.; Nillroth, U.; Karlén, A.; Hallberg, A.; Samuelsson, B. HIV-1 Protease Inhibitors Based on Acyclic Carbohydrates. J. Org. Chem. 1998, 63, 4898-4906.
21. (a) Kim, C. U.; McGee, L. R.; Krawczyk, S. H.; Harwood: E.; Harada Y.; Swaminathan, S.; Bischofberger, N.; Chen, M. S.; Cherrington, J. M.; Xiong, S. F.; Griffin, L.; Cundy, K. C.; Lee, A.; Yu, B.; Gulnik, S.; Erickson, J. W. New series of potent, orally bioavailable, nonpeptidic cyclic sulfones as HIV-1 protease inhibitors. J. Med. Chem. 1996, 39, 3431-3434.
22. (b) Hultén, J.; Bonham, N. M.; Nillroth, U.; Hansson, T.; Zuccarello, G.; Bouzide, A.; Åqvist, J.; Classon, B.; Danielson, U. H.; Karlén, A.; Kvarnström, I.; Samuelsson, B.; Hallberg, A. Cyclic HIV-1 protease inhibitors derived from mannitol: Synthesis, inhibitory potencies, and computational predictions of binding affinities. J. Med. Chem. 1997, 40, 885-897.
23. (c) Qian, X.; Morís-Varas, F.; Fitzgerald, M. C.; Wong, C. H. C2-symmetrical tetrahydroxyazepanes as inhibitors of glycosidases and HIV/FIV proteases. Bioorg. Med. Chem. 1996, 4, 2055-2069.
24. Kempf, D. J. Design of symmetry-based peptidomimetic inhibitors of human immunodeficiency virus protease. Methods Enzymol. 1994, 241, 334-354.
25. Lam, P. Y.; Jadhav, P. K.; Eyermann, C. J.; Hodge, C. N.; Ru, Y.; Bacheler, L. T.; Meek, J. L.; Otto, M. J.; Rayner, M. M.; Wong, Y. N.; Chang, C.-H.; Weber, P. C.; Jackson, D. A.; Sharpe, T. R.; Erickson-Viitanen, S. Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science 1994, 263, 380-384.
26. SYBYL ver. 6.1, Tripos Associates, England.
27. (a) Erickson, J.; Neidhart, D. J.; VanDrie, J.; Kempf, D. J.; Wang, X. C.; Norbeck, D. W.; Plattner, J. J.; Rittenbouse, J. W.; Turon, M.; Wideburg, N.; Kohlbrenner, W. E.; Simmer, R.; Helfrich, R.; Paul, D. A.; Knigge, M. Design, activity, and 2.8.ANG. crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease. Science 1990, 249, 527-533.
28. (b) Bernstein, F. C.; Koetzle, T. F.; Williams, G. J. B.; Meyer, Jr., E. F.; Brice, M. D.; Rodgers, J. R.; Kennard, O.; Shimanouchi, T.; Tasumi, M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J. Mol. Biol. 1977, 112, 535-542.
29. (c) Abola, E.; Bernstein, F. C.; Bryant, S. H.; Koetzle, T. F.; Weng, J. Protein Data Bank. In Crystallographic Databases - Information Content, Software Systems, Scientific Applications; Allen, F. H., Bergerhoff, G., Sievers, R., Eds.; Data Commission of the International Union of Crystallography: Bonn, 1987; pp 107-132.
30. Le Merrer, Y.; Duréault, A.; Greek, C.; Micas-Languin, D.; Gravier, C.; Depezay, J. C. Synthesis of diepoxides and diaziridines, precursors of enantiomerically pure alpha-hydroxy and alpha-amino aldehydes or acids, from D-mannitol. Heteroc. 1987, 25, 541-548.
31. Chaudhary, S. K.; Hernandez, O. 4-Dimethylaminopyridine: an efficient and selective catalyst for the silylation of alcohols. Tetrahedron Lett. 1979, 99-102.
32. Bowers, A.; Halsall, T. G.; Jones, E. R. H.; Lemin, A. J. The chemistry of the triterpenes and related compounds. Part XVIII. Elucidation of the structure of polyporenic acid C. J. Chem. Soc. 1953, 2548.
33. Andersson, F.; Samuelsson, B. Pyridinium dichromate-acetic acid anhydride: A new and highly efficient reagent for the oxidation of alcohols. Carbohydr. Res. 1984, 129, C1-C3.
34. (a) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. Fast and selective oxidation of primary alcohols to aldehydes or to carboxylic acids and of secondary alcohols to ketones mediated by oxoammonium salts under two-phase conditions. J. Org. Chem. 1987, 52, 2559-2562.
35. (b) Anelli, P. L.; Banfi, S.; Montanari, F.; Quici, S. Oxidation of diols with alkali hypochlorites catalyzed by oxammonium salts under two-phase conditions. J. Org. Chem. 1989, 54, 2970-2972.
36. Poirier, V.; Calleman, C.-J. The nucleophilic reactivity of valine methylamide. A model of the N-terminal valine residues of hemoglobin Acta Chem. Scand. Ser. B 1983, 37, 817-822.
37. Ogura, H.; Kobayashi, T.; Shimizu, K.; Kawabe, K.; Takeda, K. A novel active ester synthesis reagent (N,N′-disuccinimidyl carbonate). Tetrahedron Lett. 1979, 4745-4746.
38. (a) Knorr, R.; Trzeciak, A.; Bannwarth, W.; Gillessen, D. New coupling reagents in peptide chemistry. Tetrahedron Lett. 1989, 30, 1927-1930.
39. (b) Bannwarth, W.; Schmidt, D.; Stallard, R. L.; Hornung, C.; Knorr, R.; Müller, F. Bathophenanthroline-ruthenium(II) complexes as nonradioactive labels for oligonucleotides which can be measured by time-resolved fluorescence techniques. Helv. Chim. Acta 1988, 71, 2085-2099.
40. (c) Bannwarth, W.; Knorr, R. Formation of carboxamides with N,N,N′,N′-tetramethyl(succinimido)uronium tetrafluoroborate in aqueous organic solvent systems. Tetrahedron Lett. 1991, 32, 1157-1160.
41. (a) Marsham, P. R.; Jackman, A. L.; Barker, A. J.; Boyle, F. T.; Pegg, S. J.; Wardleworth, J. M.; Kimbell, R.; O'Connor, B. M.; Calvert, A. H.; Hughes, L. R. Quinazoline antifolate thymidylate synthase inhibitors: Replacement of glutamic acid in the C2-methyl series. J. Med. Chem. 1995, 38, 994-1004.
42. (b) Kisfaludy, L.; Schón, I.; Szirtes, T.; Nyéki, O.; Lów, M. Novel and rapid peptide synthesis. Tetrahedron Lett. 1974, 1785-1786.
43. Fernandez, J. M. G.; Mellet, C. O.; Marin, A. M.; Fuentes, J. Mild and efficient procedure to remove acetal and dithioacetal protecting groups in carbohydrate derivatives using 2,3-dichloro5,6-dicyano-1,4-benzoquinone. Carbohydr. Res. 1995, 263-268.
44. Linstead, R. P.; Owen, L. N.; Webb, R. F. Elimination reactions of esters. Part III. Derivatives of dibasic polyhydroxy-acids. J. Chem. Soc. 1953, 1225-1231.
45. Iversen, T.; Bundle, D. R. Benzyl trichloroacetimidate, a versatile reagent for acid-catalyzed benzylation of hydroxy-groups. J. Chem. Soc., Chem. Commun. 1981, 1240-1241.
46. Markgren, P.-O.; Lindgren, M.; Nillroth, U.; Danielson, U. H. Identification of a reversible high affinity interaction between Cu2+ and HIV-1 proteinase residue His-69 resulting in allosteric inhibition. Submitted for publication.
47. Nillroth, U.; Besidsky, Y.; Classon, B.; Chattopadhyaya, J.; Ugi, I.; Danielsson, U. H. Specific interaction between HIV-1 proteinase and 5′-phosphate peptidomimetic derivatives of nucleoside analogues. Drug Des. Discovery 1995, 13, 43.
48. Nillroth, U.; Vrang, L.; Markgren, P.-O.; Hultén, J.; Hallberg, A.; Danielson, U. H. Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogues. Antimicrob. Agents Chemother. 1997, 41 (11), 2383-2388.
49. Classon, B.; Kvarnström, I.; Samuelsson, B.; Unge, T. Unpublished results.
50. Weislow, O. S.; Kiser, R.; Fine, D. L.; Bader, J.; Shoemaker, R. H.; Boyd, M. R. New soluble-formazan assay for HIV-1 cytopathic effects: Application to high-flux screening of synthetic and natural products for AIDS-antiviral activity. J. Natl. Cancer Inst. 1989, 81, 577-586.
51. Santi, D. V.; Danenberg, P. V. Phenylalanyl transfer ribonucleic acid synthetase from Escherichia coli. Analysis of the phenylalanine binding site. Biochemistry 1971, 10, 4813-4820.
52. Plucinski, T.; Rolka, K.; Baran, L.; Przegalinski, E.; Kupryszewski, G. Opiate-like peptides. Part III. New amides of Metenkephalin and [D-Ala]2-Met-enkephalin. Polish J. Chem. 1983, 57, 887.
53. Pavlik, M.; Kluh, I.; Pavlikova, F.; Vasickova, S.; Kostka, V. Preparation, spectral and physicochemical characteristics of methylamide Nα-phenylthiocarbamoyl derivatives of naturally occurring amino acids. Collect. Czech. Chem. Commun. 1989, 54, 1940-1954.