2,4,6-Trisubstituted triazines as protein A mimetics for the treatment of autoimmune diseases

Journal of Medicinal Chemistry

Volumn 53, Issue 3, 2010, Pages 1138-1145

  Zacharie, Boulos ^a   Abbott, Shaun D ^a   Bienvenu, Jean François ^a   Cameron, Alan D ^a   Cloutier, Josée ^a   Duceppe, Jean Simon ^a   Ezzitouni, Abdallah ^a   Fortin, Daniel ^a   Houde, Karine ^a   Lauzon, Caroline ^a   Moreau, Nancie ^a   Perron, Valérie ^a   Wilb, Nicole ^a   Asselin, Michel ^a   Doucet, André ^a   Fafard, Marie Ève ^a   Gaudreau, Dannyck ^a   Grouix, Brigitte ^a   Sarra Bournet, François ^a   St Amant, Natalie ^a   Gagnon, Lyne ^a   Penney, Christopher L ^a   more..

^a ProMetic Life Sciences Inc   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

1,3 PHENYLENEDIAMINE; 2 [(3 TERT BUTOXYCARBONYLAMINOPHENYL)AMINO] 4,6 DICHLORO[1,3,5]TRIAZINE; 2 [4 (3 AMINOPHENYLAMINO) 6 [4 [2 [4 (3 AMINOPHENYLAMINO 6 (2 HYDROXYETHYLAMINO)[1,3,5]TRIAZIN 2 YLAMINO)ETHYL]PHENYLAMINO][1,3,5]TRIAZIN 2 YLAMINO]ETHANOL; 2 [4 [(3 TERT BUTOXYCARBONYLAMINOPHENYL)AMINO] 6 [2 [4 [4 [(3 TERT BUTOXYCARBONYLAMINOPHENYL)AMINO] 6 CHLORO[1,3,5]TRIAZINE 2 YLAMINO]PHENYL]ETHYLAMINO][1,3,5]TRIAZINE 2 YLAMINO]ETHANOL; 2 [4 [(3 TERT BUTOXYCARBONYLAMINOPHENYL)AMINO] 6 [4 [2 [4 [(3 TERT BUTOXYCARBONYLAMINOPHENYL)AMINO] 6 (2 HYDROXYETHYLAMINO)[1,3,5]TRIAZIN 2 YLAMINO]ETHYL]PHENYLAMINO][1,3,5]TRIAZIN 2 YLAMINO]ETHANOL; 2 [4 [(3 TERT BUTOXYCARBONYLAMINOPHENYL)AMINO] 6 CHLORO[1,3,5]TRIAZINE 2 YLAMINO]ETHANOL; 2 [4 [2 (4 AMINOPHENYL)ETHYLAMINO] 6 [(3 TERT BUTOXYCARBONYLAMINOPHENYL)AMINO][1,3,5]TRIAZINE 2 YLAMINO]ETHANOL; 2 AMINOPHENETHYLAMINE; 2,4,6 TRIAZINE DERIVATIVE; 3 AMINOPHENETHYLAMINE; 3 METHYLSULFONYLANILINE; 4 AMINOANILINE; 4 AMINOPHENETHYLAMINE; AMINOANILINE; AMINOBENZYLAMINE; IMMUNOGLOBULIN G ANTIBODY; META TYRAMINE; N,N DIMETHYLAMINOETHYLAMINE; PHENYLENEDIAMINE DERIVATIVE; PIPERAZINE; PYRROLINE; STAPHYLOCOCCUS PROTEIN A; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOIMMUNE DISEASE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG SYNTHESIS; MOLECULAR WEIGHT; MOUSE; NONHUMAN; PROTEIN BINDING; STRUCTURE ACTIVITY RELATION; SYSTEMIC LUPUS ERYTHEMATOSUS;

ANIMALS; ANTIBODIES, ANTINUCLEAR; BIOMIMETIC MATERIALS; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; IMMUNOGLOBULIN G; KIDNEY; LUPUS ERYTHEMATOSUS, SYSTEMIC; MICE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN CONFORMATION; STAPHYLOCOCCAL PROTEIN A; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZINES;

EID: 77249094567     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm901403r     Document Type: Article

References (37)

1. (a) Langone, J. J. Protein A of Staphylococcus aureus and related immunoglobulin receptors produced by streptococci and pneumococci. Adv. Immunol. 1982, 32, 157-252.
2. (b) Nilsson, B.; Abrahmsén, L. Fusions to staphylococcal protein A. Methods Enzymol. 1990, 185, 144-161.
3. (c) Moks, T.; Abrahmsén, L.; Nilsson, B.; Hellman, U.; Sjoquist, J.; Uhlén, M. Staphylococcal protein A consists of five IgGbinding domains. Eur. J. Biochem. 1986, 156, 637-643.
4. Delano, W.; Ultsch, M.; de Vos, A. M.; Wells, J. A. Convergent solutions to binding at a protein-protein interface. Science 2000, 287, 1279-1283 and references cited therein.
5. (a) Li, R.; Dowd, V.; Stewart, D. J.; Burton, J.; Lowe, C. R. Design, Synthesis, and application of a proteinA mimetic. Nat. Biotechnol. 1998, 16, 190-195.
6. (b) Fassina, G.; Ruvo, M.; Palombo, G.; Verdoliva, A.; Marino, M. Novel ligands for the affinity-chromatographic purification of antibodies. J. Biochem. Biophys. Methods 2001, 49, 481-490.
7. McCormick, D. Bioseparations look ahead to the past. Pharm. Technol. 2005, 29, 36-44.
8. Godfrey, M. A.; Kwasowski, P.; Clift, R.; Marks, V. Assessment of the suitability of commercially available SpA affinity solid phases for the purification of murine monoclonal antibodies at process scale. J. Immunol. Methods 1993, 160, 97-105.
9. Teng, S.; Sproule, K.; Hussain, A.; Lowe, C. R. A strategy for the generation of biomimetic ligands for affinity chromatography. Combinatorial synthesis and biological evaluation of an IgG binding ligand. J. Mol. Recognit. 1999, 12, 67-75.
10. (a) Delano, W. L.; Ultsch, M. H.; de Vos, A. M.; Wells, J. A. Convergent solutions to binding at a protein - protein interface. Science 2000, 287, 1279-1283.
11. (b) Ehrlich, G. K.; Bailon, P. Identification of model peptides as affinity ligands for the purification of humanized monoclonal antibodies by means of phage display. J. Biochem. Biophys. Methods 2001, 49, 443-454.
12. (c) Fassina, G.; Verdoliva, A.; Oderna,M. R.; Ruvo, M.; Cassini, G. Protein A mimetic peptide ligand for affinity purification of antibodies. J. Mol. Recognit. 1996, 9, 564-569.
13. Johnson, C. P.; Jensen, I. E.; Prakasam, A.; Vijayendran, R.; Leckband, D. Engineered Protein A for the orientational control of immobilized proteins. Bioconjugate Chem. 2003, 14, 974-978.
14. (a) Sasso, E. H.; Merrill, C.; Furst, D. E. Immunoglobulin binding properties of the prosorba immunadsorption column in treatment of rheumatoid arthritis. Ther. Apheresis 2001, 5, 84-91.
15. (b) Brunner, J.; Kern, P. M.; Gaipl, U. S.; Voll, R. E.; Kalden, J. R.; Wiesenhutter, C. W.; Hermann, M. The low-throughput protein A adsorber: an immune modulatory device. Hypothesis for the mechanism of action in the treatment of rheumatoid arthritis. Mod. Rheumatol. 2005, 15, 9-18.
16. Silverman, G.; Goodyear, C. S.; Siegel, D. L. On the mechanism of staphylococcal protein A immunomodulation. Transfusion 2005, 45, 274-280.
17. Zacharie, B.; Fortin, F.; Wilb, N.; Bienvenu, J.-F.; Asselin, M.; Grouix, B.; Penney, C. 2,6,9-Trisubstituted purine derivatives as protein A mimetics for the treatment of autoimmune diseases. Bioorg. Med. Chem. 2009, 19, 242-246.
18. Blotny, G. Recent applications of 2,4,6-trichloro-1,3,5-triazine and its derivatives in organic synthesis. Tetrahedron 2006, 62, 9507-9522 and references cited therein.
19. Baliani, A.; Bueno, G. J.; Stewart, M. L.; Yardlev, V.; Brun, R.; Barrett, M. P.; Gilbert, I. H. Design and synthesis of a series of melamine-based nitroheterocycles with activity against Trypanosomatid parasites. J. Med. Chem. 2005, 48, 5570-5579.
20. (a) Menicagli, R.; Samaritani, S.; Signore, G.; Vaglini, F.; Via, L. D. In vitro cytotoxic activities of 2-alkyl-4,6-diheteroalkyl-1,3,5-triazines: new molecules in anticancer research. J. Med. Chem. 2004, 47, 4649-4652.
21. (b) Kawashima, S.; Matsuno, T.; Yaguchi, S.; Sasahara, H.; Watanabe, T. Heterocyclic Compound and Antitumor Agent Containing the Same as Active Ingredient U.S. Patent 7,071,189, 2006.
22. (c) Matsuno, T.; Kato, M.; Sasahara, H.;Watanabe, T.; Inaba, M.; Takahashi, M.;Yaguchi, S.-I.;Yoshioka, K.; Sakato, M.; Kawashima, S. Synthesis and antitumor activity of benzimidazolyl-1,3,5-triazine and benzimidazolylpyrimidine derivatives. Chem. Pharm. Bull. 2000, 48, 1778-1781.
23. (d) Moon, H.-S.; Jacobson, E. M.; Khersonsky, S. M.; Luzung, M. R.;Walsh, D. P.; Xiong,W.; Lee, J.W.; Parikh, P. B.; Lam, J. C.; Kang, T.-W.; Rosania, G. R.; Schier, A. F.; Chang, Y.-T. A novel microtubule destabilizing entity from orthogonal synthesis of triazine library and zebrafish embryo screening. J. Am. Chem. Soc. 2002, 124, 11608-11609.
24. (e) Arya, K.; Dandia, A. Synthesis and cytotoxic activity of trisubstituted-1,3,5-triazines. Bioorg. Med. Chem. Lett. 2007, 17, 3298-3304.
25. Melato, S.; Prosperi, D.; Coghi, P.; Basilico, B.; Monti, D. A combinatorial approach to 2,4,6-trisubstituted triazines with potent antimalarial activity: combining conventional synthesis and microwave- assistance. ChemMedChem 2008, 3, 873-876 and references cited therein.
26. Xiong, Y.-Z.; Chen, F.-E.; Balzarini, J.; De clercq, E.; Pannecouque, C. Non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 11: structural modulations of diaryltriazines with potent anti-HIV activity. Eur. J.Med. Chem. 2008, 43, 1230-1236 and references cited therein.
27. (a) Zhou, C.; Min, J.; Liu, Z.; Young, Z.; Deshazer, H.; Gao, T.; Chang, Y.-T.; Kallenbach, R. Synthesis and biological evaluation of novel 1,3,5-triazine derivatives as antimicrobial agents. Bioorg. Med. Chem. Lett. 2008, 18, 1308-1311.
28. (b) Srinivas, K.; Srinivas, U.; Bhanuprakash, K.; Harakishore, K.; Murthy, U. S. N.; Rao, V. J. Synthesis and antibacterial activity of various substituted triazines. Eur. J. Med. Chem. 2006, 41, 1240-1246.
29. Penney, C. Zacharie, B.; Abbott, S. D.; Bienvenu, J.-F.; Cameron, A. D.; Duceppe, J.-S.; Ezzitouni, A.; Fortin, D.; Houde, K.; Moreau, N.; Wilb, N.; Grouix, B.; Gagnon, L. Triazines Dimmers for the Treatment of Autoimmune Diseases. WO 2005/049607, 2005.
30. Unpublished results.
31. (a) The active site was defined by the collection residues of IgG Fc within 5 Å of bound proteinA(PDB code 1FC2). MOE was used to generate several potential docking modes, and a low energy one was chosen. Molecular dynamics (500 K; heat, 100 ps; run, 200 ps; cool, 100 ps) was used to explore the region, and the residues defining the active site were also allowed to move. The structures above show the final bound complex. It is likely that there are multiple binding modes.
32. (b) The binding site was specified to be the same as for protein A: Deisenhofer, J. Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment-b of protein A from Staphylococcus- aureus at 2.9 Å and 2.8 Å resolution. Biochemistry 1981, 20 (9), 2361-2370.
33. 1 mice with recombinant soluble Fcγ receptor II (CD32). Ann. Rheum. Dis. 2008, 67, 154-161.
34. Passwell, J.; Schreiner, G. F.; Nonaka, M.; Beuscher, H. U.; Colten, H. R. Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis. J. Clin. Invest. 1988, 82, 1676-1684.
35. (a) Shields, R. L.; Namenuk, A. K.; Hong, K.; Meng, Y. G.; Rae, J.; Briggs, J.; Xie, D.; Lai, J.; Stadlen, A.; Li, B.; Fox, J. A.; Presta, L. G. High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR. J. Biol. Chem. 2001, 276, 6591-6604.
36. (b) Wines, B. D.; Gavin, A.; Powell, M. S.; Steinitz, M.; Buchanan, R. R. C.; Hogarth, P. M. Soluble FcγRIIa inhibits rheumatoid factor binding to immune complexes. Immunology 2003, 109, 246-254.
37. Marino, M.; Ruvo, M.; De Falco, S.; Fassina, G. Prevention of systemic lupus erythematosus in MRL/lpr mice by administration of an immunoglobulin- binding peptide. Nat. Biotechnol. 2000, 18, 735-739.