Bisaryloxime ethers as potent inhibitors of transthyretin amyloid fibril formation

Journal of Medicinal Chemistry

Volumn 48, Issue 5, 2005, Pages 1576-1587

  Johnson, Steven M ^a   Petrassi, H Michael ^a   Palaninathan, Satheesh K ^b   Mohamedmohaideen, Nilofar N ^b   Purkey, Hans E ^a   Nichols, Christopher ^a   Chiang, Kyle P ^a   Walkup, Traci ^a   Sacchettini, James C ^b   Sharpless, K Barry ^a   Kelly, Jeffery W ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b TEXAS A AND M UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID; ETHER DERIVATIVE; OXIME DERIVATIVE; PREALBUMIN;

AMYLOIDOSIS; ARTICLE; CRYSTAL STRUCTURE; DISSOCIATION CONSTANT; DRUG SYNTHESIS; PROTEIN FOLDING; PROTEIN STABILITY; STOICHIOMETRY; STRUCTURE ACTIVITY RELATION;

AMYLOID; CRYSTALLOGRAPHY, X-RAY; DRUG STABILITY; ETHERS; HUMANS; HYDRAZINES; OXIMES; PREALBUMIN; PROTEIN BINDING; PROTEIN STRUCTURE, QUATERNARY; STRUCTURE-ACTIVITY RELATIONSHIP; ULTRACENTRIFUGATION;

EID: 20144365267     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049274d     Document Type: Article

References (75)

1. Sekijima, Y.; Hammarström, P.; Matsumura, M.; Shimizu, Y.; Iwata, M.; Tokuda, T.; Ikeda, S.; Kelly, J. W. Energetic Characteristics of the New Transthyretin Variant A25T May Explain Its Atypical Central Nervous System Pathology. Lab. Invest. 2003, 83, 409-417.
2. Hammarström, P.; Sekijima, Y.; White, J. T.; Wiseman, R. L.; Lim, A.; Costello, C. E.; Altland, K.; Garzuly, F.; Budka, H.; Kelly, J. W. D18G Transthyretin Is Monomeric, Aggregation Prone, and Not Detectable in Plasma and Cerebrospinal Fluid: A Prescription for Central Nervous System Amyloidosis? Biochemistry 2003, 42, 6656-6663.
3. Garzuly, F.; Wisniewski, T.; Brittig, F.; Budka, H. Familial meningocerebrovascular amyloidosis, Hungarian type, with mutant transthyretin (TTR Asp18Gly). Neurology 1996, 47, 1562-1567.
4. Ikeda, S.; Nakazato, M.; Ando, Y.; Sobue, G. Familial transthyretin-type amyloid polyneuropathy in Japan: Clinical and genetic heterogeneity. Neurology 2002, 58, 1001-1007.
5. Westermark, P.; Sletten, K.; Johansson, B.; Cornwell, G. G., III. Fibril in senile systemic amyloidosis is derived from normal transthyretin. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 2843-2845.
6. Jacobson, D. R.; Pastore, R. D.; Yaghoubian, R.; Kane, I.; Gallo, G.; Buck, F. S.; Buxbaum, J. N. Variant-Sequence Transthyretin (Isoleucine 122) In Late-Onset Cardiac Amyloidosis In Black Americans. N. Engl. J. Med. 1997, 336, 466-473.
7. Sipe, J. D. Amyloidosis. Crit. Rev. Clin. Lab. Sci. 1994, 31, 325-354.
8. White, J. T.; Kelly, J. W. Support for the multigenic hypothesis of amyloidosis: The binding stoichiometry of retinol-binding protein, vitamin A, and thyroid hormone influences transthyretin amyloidogenicity in vitro. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 13019-13024.
9. Hammarström, P.; Jiang, X.; Hurshman, A. R.; Powers, E. T.; Kelly, J. W. Sequence-dependent denaturation energetics: A major determinant in amyloid disease diversity. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 16427-16432.
10. Herlenius, G.; Wilczek, H. E.; Larsson, M.; Ericzon, B.-O. Ten Years of International Experience With Liver Transplantation For Familial Amyloidotic Polyneuropathy: Results From the Familial Amyloidotic Polyneuropathy World Transplant Registry. Transplantation 2004, 77, 64-71.
11. Olofsson, B.-O.; Backman, C.; Karp, K.; Suhr, O. B. Progression of cardiomyopathy after liver transplantation in patients with familial amyloidotic polyneuropathy, portuguese type. Transplantation 2002, 73, 745-751.
12. Hammarström, P.; Wiseman, R. L.; Powers, E. T.; Kelly, J. W. Prevention of Transthyretin Amyloid Disease by Changing Protein Misfolding Energetics. Science 2003, 299, 713-716.
13. Coelho, T.; Carvalho, M.; Saraiva, M. J.; Alves, I.; Almeida, M. R.; Costa, P. P. A strikingly benign evolution of FAP in an individual found to be a compound heterozygote for two TTR mutations: TTR Met 30 and TTR Met 119. J. Rheumatol. 1993, 20, 179.
14. Coelho, T.; Chorão, R.; Sausa, A.; Alves, I.; Torres, M. F.; Saraiva, M. J. M. Compound heterozygotes of transthyretin Met30 and transthyretin Met119 are protected from the devastating effects of familial amyloid polyneuropathy. Neuromusc. Disord. 1996, 6, 27.
15. Sacchettini, J. C.; Kelly, J. W. Therapeutic Strategies for Human Amyloid Diseases. Nat. Rev. Drug Discuss. 2002, 1, 267-275.
16. Cohen, F. E.; Kelly, J. W. Therapeutic approaches to protein-misfolding diseases. Nature 2003, 426, 6968, 905-909.
17. De Lorenzi, E.; Giorgetti, S.; Grossi, S.; Merlini, G.; Caccialanze, G.; Bellotti, V. Pharmaceutical Strategies Against Amyloidosis: Old and New Drugs in Targeting a "Protein Misfolding Disease." Curr. Med. Chem. 2004, 11, 1065-1084.
18. Hardy, J.; Selkoe, D. J. The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics. Science 2002, 297, 353-356.
19. Ray, S. S.; Lansbury, P. T., Jr. A possible therapeutic target for Lou Gehrig's disease. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5701-5702.
20. Miller, S. R.; Sekijima, Y.; Kelly, J. W. Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab. Invest. 2004, 84, 545-552.
21. Blake, C. C.; Geisow, M. J.; Swan, I. D. A.; Rerat, C.; Rerat, B. Structure of Human Plasma Prealbumin at 2.5 Å Resolution: A Preliminary Report on the Polypeptide Chain Conformation, Quaternary Structure and Thyroxine Binding. J. Mol. Biol. 1974, 88, 1-12.
22. Blake, C. C.; Geisow, M. J.; Oatley, S. J.; Rerat, B.; Rerat, C. Structure of Prealbumin: Secondary, Tertiary and Quaternary Interactions Determined by Fourier Refinement at 1.8 Å. J. Mol. Biol. 1978, 121, 339-56.
23. Bartalena, L.; Robbins, J. Thyroid Hormone Transport Proteins. Clin. Lab. Med. 1993, 13, 583-598.
24. Schreiber, G.; Richardson, S. J. The Evolution of Gene Expression, Structure and Function of Transthyretin. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 1997, 116, 137-160.
25. Stockigt, J. R. Thyroid Hormone Binding and Metabolism. Endocrinology, Fourth Ed. Degroot, L. J., Jameson, J. L., Eds.; W. B. Saunders Co.: Philadelphia, 2001; Vol. 2, Chapter 94, pp 1314-1326.
26. Colon, W.; Kelly, J. W. Partial Denaturation of Transthyretin Is Sufficient for Amyloid Fibril Formation in Vitro. Biochemistry 1992, 31, 8654-8660.
27. Hammarström, P.; Schneider, F.; Kelly, J. W. Trans-Suppression of Misfolding in an Amyloid Disease. Science 2001, 293, 2459-2462.
28. Lai, Z.; Colon, W.; Kelly, J. W. The Acid-Mediated Denaturation Pathway of Transthyretin Yields a Conformational Intermediate That Can Self-Assemble into Amyloid. Biochemistry 1996, 35, 6470-6482.
29. Lashuel, H. A.; Lai, Z.; Kelly, J. W. Characterization of the Transthyretin Acid Denaturation Pathways by Analytical Ultracentrifugation: Implications for the Wild-Type, V30M, and L55P Amyloid Fibril Formation. Biochemistry 1998, 37, 17851-17864.
30. Jiang, X.; Smith, C. S.; Petrassi, H. M.; Hammarström, P.; White, J. T.; Sacchettini, J. C.; Kelly, J. W. An Engineered Transthyretin Monomer that Is Nonamyloidogenic, Unless It Is Partially Denatured. Biochemistry 2001, 40, 11442-11452.
31. Liu, K; Cho, H. S.; Lashuel, H. A.; Kelly, J. W.; Wemmer, D. E. A glimpse of a possible amyloidogenic intermediate of transthyretin. Nat. Struct. Biol. 2000, 7, 754-757.
32. Miroy, G. J.; Lai, Z.; Lashuel, H. A.; Peterson, S. A.; Strang, C.; Kelly, J. W. Inhibiting transthyretin amyloid fibril formation via protein stabilization. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 15051-15056.
33. Peterson, S. A.; Klabunde, T.; Lashuel, H.; Purkey, H.; Sacchettini, J. C.; Kelly, J. W. Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 12956-12960.
34. Petrassi, H. M.; Johnson, S. M.; Purkey, H. E.; Chiang, K. P.; Walkup, T.; Jiang, X.; Powers, E. T.; Kelly, J. W. Potent and Selective Structure-Based Dibenzofuran Inhibitors of Transthyretin Amyloidogenesis: Kinetic Stabilization of the Native State. J. Am. Chem. Soc. In press.
35. Purkey, H. E.; Palaninathan, S. K.; Kent, K. C.; Smith, C.; Safe, S. H.; Sacchettini, J. C.; Kelly, J. W. Hyrdoxylated Polychlorinated Biphenyls Selectively Bind Transthyretin in Blood and Inhibit Amyloidogenesis: Rationalizing Rodent PCB Toxicity. Chem. Biol. 2004, 11, 1719-1728.
36. Adamski-Werner, S. L.; Palaninathan, S. K.; Sacchettini, J. C.; Kelly, J. W. Diflunisal Analogues Stabilize the Native State of Transthyretin. Potent Inhibition of Amyloidogenesis. J. Med. Chem. 2004, 47, 355-374.
37. Green, N. S.; Palaninathan, S. K.; Sacchettini, J. C.; Kelly, J. W. Synthesis and Characterization of Potent Bivalent Amyloidosis Inhibitors That Bind Prior to Transthyretin Tetramerization. J. Am. Chem. Soc. 2003, 125, 13404-13414.
38. Petrassi, H. M.; Klabunde, T.; Sacchettini, J.; Kelly, J. W. Structure-Based Design of N-Phenyl Phenoxazine Transthyretin Amyloid Fibril Inhibitors. J. Am. Chem. Soc. 2000, 122, 2178-2192.
39. Baures, P. W.; Peterson, S. A.; Kelly, J. W. Discovering Transthyretin Amyloid Fibril Inhibitors by Limited Screening. Bioorg. Med. Chem. 1998, 6, 1389-1401.
40. Oza, V. B.; Petrassi, H. M.; Purkey, H. E.; Kelly, J. W. Synthesis and Evaluation of Anthranilic Acid-Based Transthyretin Amyloid Fibril Inhibitors. Bioorg. Med. Chem. Lett. 1999, 9, 1-6.
41. Baures, P. W.; Oza, V. B.; Peterson, S. A.; Kelly, J. W. Synthesis and Evaluation of Inhibitors of Transthyretin Amyloid Formation Based on the Nonsteroidal Antiinflammatory Drug, Flufenamic Acid. Bioorg. Med. Chem. 1999, 7, 1339-1347.
42. Klabunde, T.; Petrassi, H. M.; Oza, V. B.; Raman, P.; Kelly, J. W.; Sacchettini, J. C. Rational design of potent human transthyretin amyloid disease inhibitors. Nat. Struct. Biol. 2000, 7, 312-321.
43. Oza, V. B.; Smith, C.; Raman, P.; Koepf, E. K.; Lashuel, H. A.; Petrassi, H. M.; Chiang, K. P.; Powers, E. T.; Sacchettini, J.; Kelly, J. W. Synthesis, Structure, and Activity of Diclofenac Analogues as Transthyretin Amyloid Fibril Formation Inhibitors. J. Med. Chem. 2002, 45, 321-332.
44. Razavi, H.; Palaninathan, S. K.; Powers, E. T.; Wiseman, R. L.; Purkey, H. E.; Mohamedmohaideen, N. N.; Deechonkit, S.; Chiang, K. P.; Dendle, M. T. A.; Sacchettini, J. C.; Kelly, J. W. Benzoxazoles as Transthyretin Amyloid Fibril Inhibitors: Synthesis, Evaluation, and Mechanism of Action. Angew. Chem., Int. Ed. 2003, 42, 2758-2761.
45. Nazarpack-Kandlousy, N.; Zweigenbaum, J.; Henion, J.; Eliseev, A. V. Synthesis and Characterization of a Mixture-Based Library of Oxime Ethers Based on a Common Aromatic Scaffold. J. Comb. Chem. 1999, 199-206.
46. Hochgürtel, M.; Kroth, H.; Piecha, D.; Hofmann, M. W.; Nicolau, C.; Krause, S.; Schaaf, O.; Sonnenmoser, G.; Eliseev, A. V. Target-induced formation of neuraminidase inhibitors from in vitro virtual combinatorial libraries. Proc. Nat. Acad. Sci., U.S.A. 2002, 99, 3382-3387.
47. FDA approved antibacterial agents containing the oxime ether moiety were found using MDL ISIS/Base 2.5, from MDL Information Systems, Inc., and MDDR 2003.2 (25.11) database, which scans the Drug Data Report from Prous Science Publishers containing data regarding the development of pharmaceuticals.
48. Purkey, H. E.; Dorrell, M. I.; Kelly, J. W. Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 5566-5571.
49. Karabatsos, G. J.; Graham, J. D.; Vane, F. M. syn-anti Isomer Determination of 2,4-Dinitrophenylhydrazones and Semicarbazones by N.m.r. J. Am. Chem. Soc. 1962, 84, 753-755.
50. Lustig, E. A Nuclear Magnetic Resonance Study of syn-anti Isomerism in Ketoximes. J. Phys. Chem. 1961, 65, 491-495.
51. Karabatsos, G. J.; Shapiro, B. L.; Vane, F. M.; Fleming, J. S.; Ratka, J. S. Structural Studies by Nuclear Magnetic Resonance. II. Aldehyde 2,4-Dinitrophenylhydrazones. J. Am. Chem. Soc. 1963, 85, 2784-2788.
52. Karabatsos, G. J.; Taller, R. A. Structural Studies by Nuclear Magnetic Resonance. V. Phenylhydrazones. J. Am. Chem. Soc. 1963, 85, 3624-3629.
53. Sheradsky, T.; Nov, E. Studies on the Preparation of N-Alkyl-O- phenylhydroxylamines. J. Chem. Soc., Perkin Trans. 1 1980, 12, 2781-2786.
54. Karabatsos, G. J.; His, N. Structural Studies by Nuclear Magnetic Resonance-XI. Conformations and Configurations of Oxime O-Methyl Ethers. Tetrahedron 1967, 23, 1079-1095.
55. Rappoport, Z.; Sheradsky, T. The Ultraviolet Spectra of O-(2,4-Dinitrophenyl)oximes and 2,4-Dinitrophenylhydrazones: Transmission of Electronic Effects through O and NH groups. J. Chem. Soc. B, Phys. Org. 1967, 9, 898-903.
56. Abele, E.; Lukevics, E. Recent Advances in the Chemistry of Oximes. Org. Prep. Proced. Int. 2000, 32, 235-264.
57. Petrassi, H. M.; Sharpless, K. B.; Kelly, J. W. The Copper-Mediated Cross-Coupling of Phenylboronic Acids and N-Hydroxy-phthalimide at Room Temperature: Synthesis of Aryloxyamines. Org. Lett. 2001, 3, 139-142.
58. Miyazawa, E.; Sakamoto, T.; Kikugawa, Y. Preparation of Ring-Substituted Phenoxyamine Derivatives. Org. Prep. Proced. Int. 1997, 29, 594-600.
59. Choong, I. C.; Ellman, J. A. Synthesis of Alkoxylamines by Alkoxide Animation with 3,3′-Di-tert-butyloxaziridine. J. Org. Chem. 1999, 64, 6528-6529.
60. Miller, M. J.; Loudon, G. M. A Convenient, High-Yield Conversion of Aldehydes to Nitriles. J. Org. Chem. 1975, 40, 126-127.
61. Supsana, P.; Tsouongas, P. G.; Varvounis, G. A novel one-pot synthesis of isomeric naphtha[1,2-d]isoxazole-2-oxide and naphtha[1,8-de][1,2]oxazine ring systems. A case of simultaneous o- and peri-cyclisation in naphthalene. Tetrahedron Lett. 2000, 41, 1845-1847.
62. Knudsen, R. D.; Snyder, H. R. A Convenient One-Step Conversion of Aromatic Nitro Compounds to Phenols. J. Org. Chem. 1974, 39, 3343-3346.
63. Gómez, V.; Pérez-Medrano, A. Synthesis of β-Dicarbonyl Compounds via the Conjugate Addition of Benzaldoximate Anion to α,β-Acetylenic Carbonyl Compounds. J. Org. Chem. 1994, 59, 1219-1221.
64. NAr Reactions. J. Org. Chem. 1991, 56, 5513-5517.
65. Royer, R. E.; Deck, L. M.; Campos, N. M.; Hunsaker, L. A.; Vander Jagt, D. L. Biologically Active Derivatives of Gossypol: Synthesis and Antimalarial Activities of Peri-Acylated Gossylic Nitriles. J. Med. Chem. 1986, 29, 1799-1801.
66. 2. J. Org. Chem. 1986, 51, 1006-1011.
67. Blake, J. A.; Pratt, D. A.; Lin, S.; Walton, J. C.; Mulder, P.; Ingold, K. U. Thermolyses of O-Phenyl Oxime Ethers. A New Source of Iminyl Radicals and a New Source of Aryloxyl Radicals. J. Org. Chem. 2004, 69, 3112-3120.
68. Petitpas, I.; Petersen, C. E.; Ha, C. E.; Bhattacharya, A. A.; Zunszain, P. A.; Ghuman, J.; Bhagavan, N. V.; Curry, S. Structural Basis of Albumin-Thyroxine Interactions and Familial Dysalbuminemic Hyperthyroxinemia. Proc. Nat. Acad. Sci., U.S.A. 2003, 100, 6440-6445.
69. Reddy, V.; Swanson, S. M.; Segelke, B.; Kantardjieff, K. A.; Sacchettini, J. C.; Rupp, B. Effective electron-density map improvement and structure validation on a Linux multi-CPU web cluster: The TB Structural Genomics Consortium Bias Removal Web Service. Acta Crystallogr., Sect. D, Biol. Crystallogr. 2003, 59, 2200-2210.
70. Lashuel, H. A.; Wurth, C.; Woo, L.; Kelly, J. W. The Most Pathogenic Transthyretin Variant, L55P, Forms Amyloid Fibrils under Acidic Conditions and Protofilaments under Physiological Conditions. Biochemistry 1999, 38, 13560-13573.
71. Schuster, T. M.; Laue, T. M.; Editors Modern Analytical Ultracentrifugation: Acquisition and Interpretation of Data for Biological and Synthetic Polymer Systems; Birkhauser: Boston, 1994.
72. Otwinowski, Z.; Minor, W. Macromolecular Crystallography, Part A. In Methods in Enzymology, 276: Macromolecular Crystallography, Part A; Carter, C. W., Jr., Sweet, R. M., Eds.; Academic Press: New York, 1997, pp 307-326.
73. Brunger, A. T.; Adams, P. D.; Clore, G. M.; DeLano, W. L.; Gros, P.; Grosse-Kunstleve, R. W.; Jiang, J.-S.; Kuszewski, J.; Nilges, N.; Pannu, N. S.; Read, R. J.; Rice, L. M.; Simonson, T.; Warren, G. L. Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination. Acta Crystallogr., Sect. D, Biol. Crystallogr. 1998, 54, 905-921.
74. Bailey, S. The CCP4 Suite: Programs for Protein Crystallography. Acta Crystallogr., Sect. D, Biol. Crystallogr. 1994, 50, 760-763.
75. Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Refinement of Macromolecular Structures by the Maximum-Likelihood Methodology. Acta Crystallogr., Sect. D, Biol. Crystallogr. 1997, 53, 240-255.