ADME-guided design and synthesis of aryloxanyl pyrazolone derivatives to block mutant superoxide dismutase 1 (SOD1) cytotoxicity and protein aggregation: Potential application for the treatment of amyotrophic lateral sclerosis

Journal of Medicinal Chemistry

Volumn 55, Issue 1, 2012, Pages 515-527

  Chen, Tian ^a   Benmohamed, Radhia ^b   Kim, Jinho ^c,d   Smith, Karen ^e   Amante, Daniel ^c,d   Morimoto, Richard I ^a   Kirsch, Donald R ^b   Ferrante, Robert J ^c,d   Silverman, Richard B ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b Cambria Pharmaceuticals   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d VA Pittsburgh Healthcare System   (United States)

^e VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 [(2,4 DICHLORO 5 METHYLPHENYLTHIO)METHYL] 1H PYRAZOL 3(2H)ONE; 5 [(4 CHLORO 2,5 DIMETHYLPHENYLTHIO)METHYL] 1H PYRAZOL 3(2H)ONE; ARYLSULFANYL PYRAZOLONE DERIVATIVE; CMB 087229; COPPER ZINC SUPEROXIDE DISMUTASE; CYTOCHROME P450 1A2; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; MINAPRINE; POTASSIUM CHANNEL HERG; PYRAZOLONE DERIVATIVE; UNCLASSIFIED DRUG;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; CELL PROTECTION; CELL STRAIN CACO 2; CONTROLLED STUDY; DOSE RESPONSE; DRUG ABSORPTION; DRUG BRAIN LEVEL; DRUG DESIGN; DRUG DISTRIBUTION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG ELIMINATION; DRUG METABOLISM; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; LIFE EXTENSION; LIVER MICROSOME; MOUSE; NONHUMAN; POTASSIUM CURRENT; PROTEIN AGGREGATION; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; TRANSGENIC MOUSE; WILD TYPE;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; BLOOD-BRAIN BARRIER; CACO-2 CELLS; CELL MEMBRANE PERMEABILITY; CYTOCHROME P-450 ENZYME SYSTEM; DRUG DESIGN; ETHER-A-GO-GO POTASSIUM CHANNELS; ETHERS; HEK293 CELLS; HUMANS; MICE; MICROSOMES, LIVER; MUTATION; NEURONS; PYRAZOLES; PYRAZOLONES; RATS; RATS, SPRAGUE-DAWLEY; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES; SUPEROXIDE DISMUTASE;

EID: 84862907505     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2014277     Document Type: Article

References (50)

1. Bruijn, L. I.; Miller, T. M.; Cleveland, D. W. Unraveling the mechanisms involved in motor neuron degeneration in ALS Annu. Rev. Neurosci. 2004, 27, 723-749
2. Hirtz, D.; Thurman, D. J.; Gwinn-Hardy, K.; Mohamed, M.; Chaudhuri, A. R.; Zalutsky, R. How common are the "common" neurologic disorders? Neurology 2007, 68, 326-337
3. Cronin, S.; Hardiman, O.; Traynor, B. J. Ethnic variation in the incidence of ALS Neurology 2007, 68, 1002-1007
4. Haley, R. W. Excess incidence of ALS in young Gulf War veterans Neurology 2003, 61, 750-756
5. Horner, R. D.; Kamins, K. G.; Feussner, J. R.; Grambow, S. C.; Hoff-Lindquist, J.; Harati, Y.; Mitsumoto, H.; Pascuzzi, R.; Spencer, P. S.; Tim, R.; Howard, D.; Smith., T. C.; Ryan, M. A. K.; Coffman, C. J.; Kasarskis, E. J. Occurrence of amyotrophic lateral sclerosis among Gulf War veterans Neurology 2003, 61, 742-749
6. Weisskopf, M. G.; OReilly, E. J.; McCullough, M. L.; Calle, E. E.; Thun, M. J.; Cudkowicz, M.; Ascherio, A. Prospective study of military service and mortality from ALS Neurology 2005, 64, 32-37
7. Rowland, L. P.; Shneider, N. A. Amyotrophic lateral sclerosis N. Engl. J. Med. 2001, 344, 1688-1700
8. Miller, R. G.; Mitchell, J. D.; Moore, D. H. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) Amyotrophic Lateral Scler. Other Mot. Neuron Disord. 2003, 4, 191-206
9. Rosen, D. R.; Siddique, T.; Patterson, D.; Figlewicz, D. A.; Sapp, P.; Hentati, A.; Donaldson, D.; Goto, J.; ORegan, J. P.; Deng, H.; Rahmani, Z.; Krizus, A.; Mckenna-Yasek, D.; Cayabyab, A.; Gaston, S. M.; Berger, R.; Tanzi, R. E.; Halperin, J. J.; Herzfeldt, B.; Van den Bergh, R.; Hung, W.; Bird, T.; Deng, G.; Mulder, D. W.; smyth, C.; Laing, N. G.; Soriano, E.; Pericak-Vance, M. A.; Haines, J.; Rouleau, G. A.; Gusella, J.; Horvitz, H. R.; Brown, R. H., Jr. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis Nature 1993, 362, 59-62
10. Pasinelli, P.; Brown, R. H. Molecular biology of amyotrophic lateral sclerosis: insight from genetics Nat. Rev. Neurosci. 2006, 7, 710-723
11. Mulder, D. W.; Kurland, L. T.; Offord, K. P.; Beard, C. M. Familial adult motor neuron disease: amyotrophic lateral sclerosis Neurology 1986, 36, 511-517
12. Pramatarova, A.; Figlewicz, D. A.; Krizus, A.; Han, F. Y.; Ceballos-Picot, I.; Nicole, A.; Dib, M.; Meininger, V.; Brown, R. H.; Rouleau, G. A. Identification of new mutationsin the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis Am. J. Hum. Genet. 1995, 56, 592-596
13. Ryu, H.; Ferrante, R. J. Translational therapeutic strategies in amyotrophic lateral sclerosis Mini-Rev. Med. Chem. 2007, 7, 141-150
14. Andersen, P. M.; Sims, K. B.; Xin, W. W.; Kiely, R.; ONeill, G.; Ravits, J.; Pioro, E.; Harati, Y.; Brower, R. D.; Levine, J. S.; Heinicke, H. U.; Seltzer, W.; Boss, M.; Brown, R. H., Jr. Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and diputes Amyotrophic Lateral Scler. Other Mot. Neuron Disord. 2003, 4, 62-73
15. Brown, R. H., Jr.; Robberecht, W. Amyotrophic lateral sclerosis: pathogenesis Semin. Neurol. 2001, 21, 131-139
16. Newbery, H. J.; Abbott, C. M. Of mice, men and motor neurons Trends Mol. Med. 2002, 8, 88-92
17. Bruijn, L. I.; Houseweart, M. K.; Kato, S.; Anderson, K. L.; Anderson, S. D.; Ohama, E.; Reaume, A. G.; Scott, R. W.; Cleveland, D. W. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1 Science 1998, 281, 1851-1854
18. Matsumoto, G.; Stojanovic, A.; Holmber, C. I.; Kim, S.; Morimoto, R. I. Structural properties and neuronal toxicity of amyotrophic lateral sclerosis-associated Cu/Zn superoxide dismutase 1 aggregates J. Cell Biol. 2005, 171, 75-85
19. Matsumoto, G.; Kim, S.; Morimoto, R. I. Huntingtin and mutant SOD1 form aggregate structures with distinct molecular properties in human cells J. Biol. Chem. 2006, 281, 4477-4485
20. Benmohamed, R.; Arvanites, A. C.; Silverman, R. B.; Morimoto, R. I.; Ferrante, R. J.; Kirsch, D. R. Identification of compounds protective against G93A SOD1 toxicity for the treatment of amyotrophic lateral sclerosis Amyotrophic Lateral Scler. Other Mot. Neuron Disord. 2011, 12, 87-96
21. Chen, T.; Benmohamed, R.; Arvanites, A. C.; Ranaivo, H. R.; Morimoto, R. I.; Ferrante, R. J.; Watterson, D. M.; Kirsch, D. R.; Silverman, R. B. Arylsulfanyl pyrazolones block mutant SOD1-G93A aggregation. Potential application for the treatment of amyotrophic lateral sclerosis Bioorg. Med. Chem. 2011, 19, 613-622
22. Basak, A.; Barlan, A. U.; Yamamoto, H. Catalytic enantioselective oxidation of sulfides and disulfides by a chiral complex of bis-hydroxamic acid and molybdenum Tetrahedron: Asymmetry 2006, 17, 508-511
23. Zhang, W.; Yamamoto, H. Vanadium-catalyzed asymmetric epoxidation of homoallylic alcohols J. Am. Chem. Soc. 2007, 129, 286-287
24. Sonda, S.; Kawahara, T.; Murozono, T.; Sato, N.; Asona, K.; Haga, K. Design and synthesis of orally active benzamide derivatives as potent serotonin 4 receptor agonist Bioorg. Med. Chem. 2003, 11, 4225-4234
25. Banfi, L.; Casicio, G.; Ghiron, C.; Guanti, G.; Manghisi, E.; Narisano, E.; Riva, R. Microbiological enatioselecrive synthesis of (S) and (R) 4-(p -anisyloxy)-3-hydroxybutyrates as new chiral building blocks for the synthesis of β-lactam antibiotics Tetrahedron 1994, 50, 11983-11994
26. Hirner, S.; Panknin, O.; Edefuhr, M.; Somfai, P. Synthesis of aryl glycines by the α arylation of Weinreb amides Angew. Chem., Int. Ed. 2008, 47, 1907-1909
27. Gu, R.; Hameurlaine, A.; Dehaen, W. Facile one-pot synthesis of 6-monosubstituted and 6,12-disubstituted 5,11-dihydroindolo[3,2- b ]carbazoles and preparation of various functionalized derivatives J. Org. Chem. 2007, 72, 7207-7213
28. Doherty, E. M.; Fotsch, M.; Bo, Y.; Chakrabarti, P. P.; Chen, N.; Gavva, N.; Han, N.; Kelly, M. G.; Kincaid, J.; Klionsky, L.; Liu, Q.; Ognyanov, V. I.; Tamir, R.; Wang, X.; Zhu, J.; Norman, M. H.; Treanor, J. J. S. Discovery of potent, orally available vanilloid receptor-1 antagonists. Structure-activity relationship of N -aryl cinnamides J. Med. Chem. 2005, 48, 71-90
29. Hillier, M. C.; Davidson, J. P.; Martin, S. F. Cyclopropane-derived peptidomimetics. design, synthesis, and evaluation of novel ras farnesyltransferase inhibitors J. Org. Chem. 2001, 66, 1657-1671
30. Nakajima, T; Wang, R.; Elovaara, E; Gonzalez, F. J.; Gelboin, H. V.; Raunio, H.; Pelkonen, O.; Vainio, H.; Aoyama, T. Toluene metabolism by cDNA-Expressed human hepatic cytochrome P450 Biochem. Pharmacol. 1997, 53, 271-277
31. McNaney, C. A.; Drexler, D. M.; Hnatyshy, S. Y.; Zvyaga, T. A.; Knipe, J. O.; Belcastro, J. V.; Sanders, M. An automated liquid chromatography-mass spectrometry process to determine metabolic stability half-life and intrinsic clearance of drug candidates by substrate depletion Assay Drug Dev. Technol. 2008, 6, 121-129
32. Mitchell, S. C.; Waring, R. H. The early history of xenobiotic sulphoxidation Drug Metab. Rev. 1985, 16, 255-284
33. Fruetel, J.; Chang, Y.; Collins, J.; Loew, G.; Ortiz de Montellano, P. R. Thioanisole sulfoxidation by cytochrome P450cam (CYP101): experimental and calculated absolute stereochemistries J. Am. Chem. Soc. 1994, 116, 11643-11648
34. Kerns, E. H.; Di, L. Drug-like Properties: Concepts, Structure, Design, and Methods; Elsevier, Inc.; Amsterdam, 2008; p 291.
35. Zhang, W.; Benmohamed, R.; Arvanites, A. C.; Morimoto, R. I.; Ferrante, R. J.; Kirsch, D. R.; Silverman, R. B. Cyclohexane 1,3-diones and their inhibition of mutant SOD1-dependent protein aggregation and toxicity in PC12 cells. Bioorg. Med. Chem. [Online early access]. DOI: 10.1016/j.bmc.2011.11.039. Published Online: Nov 30, 2011.
36. Kerns, E. H.; Di, L. Drug-like Properties: Concepts, Structure, Design, and Methods; Elsevier, Inc.: Amsterdam, 2008; p 378.
37. Kerns, E. H.; Di, L. Drug-like Properties: Concepts, Structure Design and Methods; Elsevier, Inc.: Amsterdam, 2008; pp 288-291.
38. Press, B.; Di Grandi, D. Permeability for intestinal absorption: Caco-2 assay and related issues Curr. Drug Metab. 2008, 9 (9) 893-900
39. Ilieva, H.; Polymenidou, M.; Cleveland, D. W. Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond J. Cell Biol. 2009, 187, 761-772
40. Talber, A. M.; Transter, G. E.; Holmes, E.; Francis, P. L. Determination of drug-plasma protein binding kinetics and equilibria by chromatographic profiling: exemplification of the method using l -tryptophan and albumin Anal. Chem. 2002, 74, 446-452
41. Weisiger, R. A. Dissociation from albumin: a potentially rate-limiting step in the clearance of substances by the liver Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 1563-1567
42. Kerns, E. H.; Di, L. Drug-like Properties: Concepts, Structure, Design, and Methods; Elsevier, Inc.: Amsterdam, 2008; p 234.
43. Mei, H.; Korfmacher, W.; Morrison, R. Rapid in vivo oral screening in rats: reliability, acceptance criteria, and filtering efficiency AAPS J. 2006, 8, E493-E500
44. Bambal, R. B.; Clarke, S. E. Cytochrome P450: structure, function and application in drug discovery and development Eval. Drug Candidates Preclin. Dev. 2010, 55-107
45. Wang, B.; Zhou, S.-F. Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development Curr. Med. Chem. 2009, 16 (31) 4066-4218
46. Nagai, M.; Aoki, M.; Miyoshi, I.; Kato, M.; Pasinelli, P.; Kasai, N.; Brown, R. H., Jr.; Itoyama, Y. Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease J. Neurosci. 2001, 21, 9246-9254
47. Aoki, M.; Kato, S.; Nagai, M.; Itoyama, Y. Development of a rat model of amyotrophic lateral sclerosis expressing a human SOD1 transgene Neuropathology 2005, 25, 365-370
48. Gurney, M. E.; Pu, H.; Chiu, A. Y.; Dal Canto, M. C.; Polchow, C. Y.; Alexander, D. D.; Caliendo, J.; Hentati, A.; Kown, Y. W.; Deng, H. X.; Chen, W.; Zhai, P.; Sufit, R. L.; Siddique, T. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation Science 1994, 264, 1772-1775
49. Del Signore, S. J.; Amante, D. J.; Km, J.; Stack, E. C.; Goodrich, S.; Cormier, K.; Smith, K.; Cudkowicz, M. E.; Ferrante, R. J. Combined riluzole and sodium phenylbutylrate therapy in transgenic amyotrophic lateral sclerosis mice Amyotrophic Lateral Scler. Other Mot. Neuron Disord. 2009, 10, 85-94
50. Gurney, M. E.; Cutting, F. B.; Zhai, P.; Doble, A.; Taylor, C. P.; Andrus, P. K.; Hall, E. D. Benefit of vitamin E, riluzole, and gababapentin in a transgenic model of familial amyotrophic lateral sclerosis Ann. Neurol. 1996, 39, 147-157