Novel benzo[1,4]diazepin-2-one derivatives as endothelin receptor antagonists

Journal of Medicinal Chemistry

Volumn 47, Issue 11, 2004, Pages 2776-2795

  Bolli, Martin H ^a   Marfurt, Judith ^a   Grisostomi, Corinna ^a   Boss, Christoph ^a   Binkert, Christoph ^a   Hess, Patrick ^a   Treiber, Alexander ^a   Thorin, Eric ^a   Morrison, Keith ^a   Buchmann, Stephan ^a   Bur, Daniel ^a   Ramuz, Henri ^a   Clozel, Martine ^a   Fischli, Walter ^a   Weller, Thomas ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

1,3,4,5 TETRAHYDRO 1H BENZO[E][1,4]DIAZEPIN 2 ONE DERIVATIVE; AMBRISENTAN; DARUSENTAN; DIAZEPINE DERIVATIVE; ENDOTHELIN A RECEPTOR ANTAGONIST; ENDOTHELIN B RECEPTOR ANTAGONIST; ENDOTHELIN RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTERIAL PRESSURE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACTIVITY; DRUG DESIGN; DRUG EFFECT; DRUG IDENTIFICATION; DRUG RESEARCH; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; HYPERTENSION; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTIHYPERTENSIVE AGENTS; BENZODIAZEPINES; BIOLOGICAL AVAILABILITY; BLOOD PRESSURE; CYTOCHROME P-450 ENZYME SYSTEM; HEPATOCYTES; HUMANS; MALE; MICROSOMES, LIVER; MODELS, MOLECULAR; RATS; RATS, INBRED DAHL; RATS, WISTAR; RECEPTOR, ENDOTHELIN A; RECEPTOR, ENDOTHELIN B; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 2442704167     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm031115r     Document Type: Article

References (77)

1. Yanagisawa, M.; Kurihara, H.; Kimura, S.; Tomobe, Y.; Kobayashi, M.; Mitsui, Y.; Goto, K.; Masaki, T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988, 332, 411-415.
2. Inoue, A.; Yanagisawa, M.; Kimura, S.; Kasuya, Y.; Miyauchi, T.; Goto, K.; Masaki, T. The human endothelin family: Three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 2863-2867.
3. Rubanyi, G. M. Potential physiological and pathological significance of endothelins. Drugs Future 1992, 17, 915-936.
4. Jeng, A. Y.; Mulder, P.; Kwan, A.-L.; Battistini, B. Nonpeptidic endothelin-converting enzyme inhibitors and their potential therapeutic applications. Can. J. Physiol. Pharmacol. 2002, 80, 440-449.
5. Webb, M. L.; Meek, T. D. Inhibitors of Endothelin. Med. Res. Rev. 1997, 17, 17-67.
6. Rubanyi, G. M.; Polokoff, M. A. Endothelins: Molecular Biology, Biochemistry, Pharmacology, Physiology and Pathophysiology. Pharmacol. Rev. 1994, 46, 325-415.
7. Remuzzi, G.; Perico, N.; Benigni, A. New Therapeutics That Antagonize Endothelin: Promises and Frustrations. Nat. Rev. Drug Discovery 2002, 986-1001.
8. Filep, J. G. Endothelin Receptor Antagonists: New Perspectives in Endothelin Research. Drugs Today 1995, 31, 155-171.
9. Kedzierski, R. M.; Yanagisawa, M. Endothelin system: the double-edged sword in health and disease. Annu. Rev. Pharmacol. Toxicol. 2001, 41, 851-876.
10. Fagan, K. A.; McMurtry, I. F.; Rodman, D. M. Role of endothelin-1 in lung disease. Respir. Res. 2001, 2, 90-101.
11. Hay, D. W. P.; Compton, C. H. Endothelin Antagonists. Prog. Respir. Res. 2001, 31, 141-144.
12. Schiffrin, E. L. Role of endothelin-1 in hypertension and vascular disease. Am. J. Hypertens. 2001, 14, 83S-89S.
13. Douglas, S. A.; Ohlstein, E. H. Vascular and cardiac effects of endothelin. Handb. Exp. Pharmacol. 2001, 152, 405-451.
14. Naicker, S.; Bhoola, K. D. Endothelins: vasoactive modulators of renal function in health and disease. Pharmacol. Ther. 2001, 90, 61-88.
15. Pollock, D. M. Endothelin antagonists in the treatment of renal failure. Curr. Opin. Invest. Drugs 2001, 2, 513-520.
16. Neunteufl, T.; Berger, R.; Pcher, R. Endothelin receptor antagonists in cardiology clinical trials. Expert Opin. Invest. Drugs 2002, 11, 431-443.
17. Greenberg, B. H. Endothelin and endothelin receptor antagonists in heart failure. Congestive Heart Failure 2002, 8, 257-261.
18. Elijovich, F.; Laffer, C. L. Participation of renal and circulating endothelin in salt-sensitive essential hypertension. J. Hum. Hypertens. 2002, 16, 459-467.
19. Schiffrin, E. L. A critical review of the role of endothelial factors in the pathogenesis of hypertension. Can. J. Cardiovasc. Pharmacol. 2001, 38 (Suppl. 2), S3-S6.
20. Warner, T. D. Endothelin Receptor Antagonists. Cardiovasc. Drug Rev. 1994, 12, 105-122.
21. Ohlstein, E. H.; Elliott, J. D.; Feuerstein, G. Z.; Ruffolo, R. R. Endothelin Receptors: Receptor Classification, Novel Receptor Antagonists, and Potential Therapeutic Targets. Med. Res. Rev. 1996, 16, 365-390.
22. Botting, J. Endothelins: New Therapeutic Opportunities. Drug News Perspect. 1997, 10, 54-57.
23. Shimokawa, H. Endothelial Dysfunction as a Novel Therapeutic Target in Atherosclerosis. Drug News Perspect. 1999, 12, 271-277.
24. Spiecker, L. E.; Noll, G.; Ruschitzka, F. T.; Luscher, T. F. Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future? J. Am. Coll. Cardiol. 2001, 37, 1493-1505.
25. Rubin, L. J.; Roux, S. Bosentan: a dual endothelin receptor antagonist. Expert Opin. Invest. Drugs 2002, 11, 991-1002.
26. Kim, N. H. S.; Rubin, L. J. Endothelin in health and disease: Endothelin receptor antagonists in the management of pulmonary artery hypertension. J. Cardiovasc. Pharmacol. Ther. 2002, 7, 9-19.
27. Lassiter, L. K.; Carducci, M. A. New approaches for the prevention of bone metastases in patients with prostate cancer: A review of preclinical and clinical studies. Am. J. Cancer 2003, 2, 181-199.
28. Schulman, C. Atrasentan: the first endothelin receptor antagonist for hormone-refractory prostate cancer. Eur. Urol., Suppl. 2003, 2, 20-27.
29. Riechers, H.; Albrecht, H.-P.; Amberg, W.; Baumann, E.; Bernard, H.; Böhm, H.-J.; Klinge, D.; Kling, A.; Müller, S.; Raschak, M.; Unger, L.; Walker, N.; Wernet, W. Discovery and Optimization of a Novel Class of Orally Active Nonpeptidic Endothelin-A Receptor Antagonists. J. Med. Chem. 1996, 39, 2123-2128.
30. Billman, G. E. Ambrisentan Myogen. Curr. Opin. Invest. Drugs 2002, 3, 1483-1486.
31. Barst, R. J.; Rich, S.; Widlitz, A.; Horn, E. M.; McLaughlin, V.; McFarlin, J. Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonists, in patients with pulmonary arterial hypertension: open-label pilot study. Chest 2002, 121, 1860-1868.
32. Nakov, R.; Pfarr, E.; Eberle, S. Darusentan: an effective endothelin A receptor antagonist for treatment of hypertension. Am. J. Hypertens. 2002, 15, 583-589.
33. Cosenzi, A. Enrasentan, an antagonist of endothelin receptors. Cardiovasc. Drug Rev. 2003, 21, 1-16.
34. Munter, K.; Kirchengast, M. The role of endothelin receptor antagonists in cardiovascular pharmacotherapy. Emerging Drugs 2001, 6, 3-11.
35. Seed, A.; Love, M. P.; McMurray, J. Clinical experience with endothelin receptor antagonists in chronic renal failure. Heart Failure Rev. 2001, 6, 317-323.
36. Spieker, L. E.; Noll, G.; Ruschitzka, F. T.; Luscher, T. F. Endothelin A receptor antagonists in constive heart failure: blocking the beast while leaving the beauty untouched? Heart Failure Rev. 2001, 6, 301-315.
37. Bagnall, A.; Webb, D. Are selective endothelin A receptor antagonists better than mixed antagonists? J. Cardiovasc. Pharmacol. 2001, 38, S43-S46.
38. Clozel, M. Effects of bosentan on cellular processes involved in pulmonary arterial hypertension: do they explain the long-term benefit? Ann. Med., in press.
39. Boss, C.; Bolli, M.; Weller, T. Endothelin Receptor Antagonists: Structures, Synthesis, Selectivity and Therapeutic Applications. Curr. Med. Chem. 2002, 9, 349-383.
40. Dasgupta, F.; Mukherjee, A. K.; Gangadhar, N. Endothelin Receptor Antagonists-An Overview. Curr. Med. Chem. 2002, 9, 549-575.
41. Amberg, W.; Kling, A.; Klinge, D.; Riechers, H.; Hergenroder, S.; Raschack, M.; Unger, L. Novel beta-amino and beta-azidocarboxylic acid derivatives, the production thereof and their use as endothelin receptor antagonists. BASF AG: WO 98/58916, 1998.
42. Amberg, W.; Jansen, R.; Kettschau, G.; Riechers, H.; Baumann, E.; Hegenroder, S.; Raschack, M.; Unger, L. Novel beta-amide and beta-sulfonamide carboxylic acid derivatives, their preparation and their use as endothelin receptor antagonists. BASF AG: WO 00/37450, 2000.
43. Amberg, W.; Kettschau, G. Novel carbamates and carbamides, production and use thereof as endothelin receptor antagonists. BASF AG: WO 01/90079, 2001.
44. Klinge, D.; Unger, L.; Raschack, M.; Wernet, W. Bicyclene derivatives, their production and use. BASF AG: WO 095/15963, 1995.
45. Cheng, M. G.; Fang, J.-M. Liquid-Phase Combinatorial Synthesis of 1,4-Benzodiazepine-2-5-diones as the Candidates of Endothelin Receptor Antagonism. J. Comb. Chem., in press.
46. Hubschwerlen, C.; Schmid, G. An enantioselective β-lactam synthesis starting from L-(S)-glyceraldehyde acetonide. Helv. Chim. Acta 1983, 66, 2206-2209.
47. Cainelli, G.; Galletti, P.; Giacomini, D. Synthesis of Beta-Lactams via [2 + 2] Cycloaddition Reactions; Società Chimica Italiana: Rome, 1999.
48. Palomo, C.; Aizpurua, J. M.; Ganboa, I.; Oiarbide, M. Asymmetric Synthesis of β-Lactams by Staudinger Ketene-Imine Cycloaddition Reaction. Eur. J. Org. Chem. 1999, 3223-3235.
49. Shridhar, D. R.; Ram, B.; Narayana, V. L. A Convenient Annelation of Imines to α-Substituted β-Lactams. Synthesis 1982, 63-65.
50. Sternbach, L. H.; Fryer, R. I.; Metlesics, W.; Reeder, E.; Sach, G.; Saucy, G.; Stempel, A. Quinazolines and 1,4-Benzodiazepines. VI. Halo-, Methyl-, and Methoxy-Substituted 1,3-Dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones. J. Org. Chem. 1962, 27, 3788-3796.
51. Reeder, E.; Sternbach, L. H. Amino Substituted Benzophenone Oximes and Derivatives Thereof (Hoffmann-LaRoche Inc.). U.S. Patent 3,136,815, 1964.
52. Bock, M. G.; DiPardo, R. M.; Evans, B. E.; Rittle, K. E.; Veber, D. F. Synthesis and Resolution of 3-Amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones. J. Org. Chem. 1987, 52, 3232-3239.
53. Georg, G. I.; Ravikumar, V. T. The Organic Chemistry of β-Lactams; VCH Publishers: New York, 1992.
54. Schlüter, G.; Meise, W. Herstellung von 1-Phenyl-2-benzazepin-derivaten durch Bischler-Napieralski-Reaktion (Production of 1-Phenyl-2-benzazepine Derivatives by Bischler-Napieralski Reaction). Liebigs Ann. Chem. 1988, 833-837.
55. Bremner, J. B.; Browne, E. J.; Gunawardana, I. W. K. Synthesis of 5-Aryl-1,4-benzooxazepine and 6-Phenyl-2H-1,5-benzoxazocine Derivatives. Aust. J. Chem. 1984, 37, 129-141.
56. Walser, A.; Flynn, T.; Mason, C.; Crowley, H.; Maresca, C.; Yaremko, B.; O'Donnell, M. Triazolobenzo- and Triazolothienodiazepines as Potent Antagonists of Platelet Activating Factor. J. Med. Chem. 1991, 34, 1209-1221.
57. Hester, J. B.; Voigtlander, P. V. 6-Aryl-4H-s-triazolo[4,3-α ][1,4]-benzodiazepines. Influence of 1-Substitution on Pharmacological Activity. J. Med. Chem. 1979, 22, 1390-1398.
58. Fryer, R. I.; Earley, J. V.; Gilman, N. W.; Zally, W. Quinazolines and 1,4-Benzodiazepines. LXXIII. The Ring Expansion of 2-Chloromethylquinazoline 3-Oxides with Nitromethane. J. Heterocycl. Chem. 1976, 13, 433-437.
59. Walser, A.; Flynn, T.; Mason, C.; Fryer, R. I. Quinazolines and 1,4-Benzodiazepines, XCV[1]. Synthesis of 1,4-Benzodiazepines by Ring Expansion of 2-Chloromethylquinazolines with Carbanions. J. Heterocycl. Chem. 1986, 23, 1303-1314.
60. Manhas, M. S.; Amin, S. G.; Chawla, H. P. S.; Bose, A. K. Synthesis of α-Hydroxy-β-Lactams(I). J. Heterocycl. Chem. 1978, 15, 601-604.
61. Berger, L.; Sternbach, L. H. 2-Amino-5-cycloalkyl-3H-1,4-benzodiazepine-4-oxides (Hoffmann-La Roche Inc.); U.S. Patent 3,-179,656, 1965.
62. Zhang, W.; Koehler, K. F.; Harris, B.; Skolnick, O.; Cook, J. M. Synthesis of Benzo-Fused Benzodiazepines Employed as Probes of the Agonist Pharmacophore of Benzodiazepine Receptors. J. Med. Chem. 1994, 37, 745-757.
63. Fryer, R. I.; Gu, Z.-Y.; Wang, C.-G. Synthesis of Novel, Substituted 4H-Imidazo[1,5-α][1,4]benzodiazepines. J. Hetercycl. Chem. 1991, 28, 1661-1669.
64. Saucy, G.; Sternbach, L. H. Chinazoline und 1,4-Benzodiazepine VII. Trifluormethyl-substituierte Verbindungen (Quinazolines and 1,4-Benzodiazepines. VII. Trifluoromethyl Substituted Derivatives). Helv. Chim. Acta 1962, 45, 2226-2241.
65. VanDort, M. E.; Ciliax, B. J.; Gilderseeve, D. L.; Sherman, P. S.; Rosenspire, K. C.; Young, A. B.; Junck, L.; Wieland, D. M. Radioiodinated Benzodiazepines: Agents for Mapping Glial Tumors. J. Med. Chem. 1988, 31, 2081-2086.
66. Breu, V.; Löffler, B. M.; Clozel, M. In vitro characterization of Ro 46-2005, a novel synthetic non-peptide endothelin antagonist of ETA and ETB receptors. FEBS Lett. 1993, 334, 210-214.
67. Clozel, M.; Breu, V.; Gray, G. A.; Kalina, B.; Löffler, B.-M.; Burri, K.; Cassal, J.-M.; Hirth, G.; Müller, M.; Neidhart, W.; Ramuz, H. Pharmacological Characterisation of Bosentan, a New Potent Orally Active Nonpeptide Endothelin Receptor Antagonist. J. Pharmacol. Exp. Ther. 1994, 270, 228-235.
68. Brockway, B. P.; Mills, P. A.; Azar, S. H. A New Method for Continuous Chronic Measurement and Recording of Blood Pressure, Heart Rate and Activity in the Rat via Radio-Telemetry. Clin. Exp. Hypertens., Part A 1991, 13, 885-895.
69. Guiol, C.; Ledoussal, C.; Surgé, J.-M. A Radiotelemetry System for Chronic Measurement of Blood Pressure and Heart Rate in the Unrestrained Rat Validation of the Method. J. Pharmcol. Toxicol. Methods 1992, 28, 99-105.
70. Hess, P.; Clozel, M.; Clozel, J.-P. Telemetry monitoring of pulmonary arterial pressure in freely moving rats. J. Appl. Physiol. 1996, 81, 1027-1032.
71. Löffler, B.-M.; Breu, V.; Clozel, M. Effect of different endothelin receptor antagonists and of the novel non-peptide antagonist Ro 46-2005 on endothelin levels in rat plasma. FEBS Lett. 1993, 333, 108-110.
72. Leemann, T.; Transon, C.; Dayer, P. Cytochrome P450TB (CYP2C): a major monooxygenase catalyzing diclofenac-4′-hydroxylation in human liver. Life Sci. 1993, 52, 29-34.
73. Fischer, V.; Vogels, B.; Maurer, G.; Tynes, R. E. The antipsychotic clozapine is metabolized by the polymorphic human microsomal and recombinant cytochrome P450 2D6. J. Pharmacol. Exp. Ther. 1992, 260, 1355-1360.
74. Kronbach, T.; Mathys, D.; Umeno, M.; Gonzalez, F. J.; Meyer, U. A. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol. Pharmacol. 1989, 36, 89-96.
75. Gerber, P. R. Charge distribution from a simple molecular orbital type calculation and non-bonding interaction terms in the force field MAB J. Comput.-Aided Mol. Des. 1998, 12, 37-51 (www.moloc.ch).
76. Luethy, R.; Bowie, J. U.; Eisenberg, D. Assessment of protein models with three-dimensional profiles. Nature 1992, 356, 83-85.
77. Partition Coefficient (n-Octanol/Water): Shake Flask Method. OECD Guidelines for the Testing of Chemicals; Organisation for Economic Co-Operation and Development: Paris, July 27, 1995; No. 107.