Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ET(A) antagonist (A-216546)

Journal of Medicinal Chemistry

Volumn 41, Issue 17, 1998, Pages 3261-3275

  Liu, Gang ^a   Henry Jr , Kenneth J ^a,b   Szczepankiewics, Bruce G ^a   Winn, Martin ^a   Kozmina, Natasha S ^a   Boyd, Steven A ^a   Wasicak, James ^a   Von Geldern, Thomas W ^a   Wu Wong, Jinshyun R ^a   Chiou, William J ^a   Dixon, Douglas B ^a   Nguyen, Bach ^a   Marsh, Kennan C ^a   Opgenorth, Terry J ^a  

^a ABBOTT LABORATORIES   (United States)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [2 (2 OXOPYRROLIDIN 1 YL)ETHYL] 4 (1,3 BENZODIOXOL 5 YL) 1 [(N,N DIBUTYLAMINO)CARBONYLMETHYL]PYRROLIDINE 3 CARBOXYLIC ACID; 2 [2 (2 PYRIDYL)ETHYL] 4 (1,3 BENZODIOXOL 5 YL) 1 [(N,N DIBUTYLAMINO)CARBONYLMETHYL]PYRROLIDINE 3 CARBOXYLIC ACID; 2 [2,2 DIMETHYL 3 PENTENYL] 4 (7 METHOXY 1,3 BENZODIOXOL 5 YL) 1 [(N,N DIBUTYLAMINO)CARBONYLMETHYL]PYRROLIDINE 3 CARBOXYLIC ACID; A 216546; ATRASENTAN; ENDOTHELIN A RECEPTOR; ENDOTHELIN A RECEPTOR ANTAGONIST; ENDOTHELIN B RECEPTOR; PYRROLIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; CHO CELL; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG GLUCURONIDATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; HYDROPHOBICITY; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; BINDING, COMPETITIVE; BIOLOGICAL AVAILABILITY; CHO CELLS; CRICETINAE; DRUG DESIGN; HUMANS; KINETICS; MALE; METABOLIC CLEARANCE RATE; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; PYRROLIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, ENDOTHELIN A; RECEPTOR, ENDOTHELIN B; RECEPTORS, ENDOTHELIN; RECOMBINANT PROTEINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSFECTION;

EID: 15144360873     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980217s     Document Type: Article

References (38)

1. Yanagisawa, M.; Kurihara, H.; Kimura, S.; Tomobe, Y.; Kobayashi, M.; Mitsui, Y.; Yazaki, 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. For recent reviews on the endothelin system, see: (a) Doherty, A. M. Endothelin: A New Challenge. J. Med. Chem. 1992, 35, 1493-1508. (b) Shiosaki, K. Recent Advances in Endothelin Receptor Antagonists. Exp. Opin. Ther. Pat. 1994, 4, 1361-1365. (c) Opgenorth, T. J. Endothelin Receptor Antagonism. Adv. Pharmacol. 1995, 33, 1-65. (d) Williams, D. L.; Walsh, T. F. Endothelin Blockade and Hypertension. In Antihypertensive Drugs; van Zwieten, P. A., Greenlee, W. J., Eds.; Harwood Academic: Amsterdam, 1997; pp 213-280. (e) Lago, M. A.; Luengo, J. I. Endothelin Antagonists. Annu. Rep. Med. Chem. 1996, 31, 81-90.
4. For recent reviews on the endothelin system, see: (a) Doherty, A. M. Endothelin: A New Challenge. J. Med. Chem. 1992, 35, 1493-1508. (b) Shiosaki, K. Recent Advances in Endothelin Receptor Antagonists. Exp. Opin. Ther. Pat. 1994, 4, 1361-1365. (c) Opgenorth, T. J. Endothelin Receptor Antagonism. Adv. Pharmacol. 1995, 33, 1-65. (d) Williams, D. L.; Walsh, T. F. Endothelin Blockade and Hypertension. In Antihypertensive Drugs; van Zwieten, P. A., Greenlee, W. J., Eds.; Harwood Academic: Amsterdam, 1997; pp 213-280. (e) Lago, M. A.; Luengo, J. I. Endothelin Antagonists. Annu. Rep. Med. Chem. 1996, 31, 81-90.
5. For recent reviews on the endothelin system, see: (a) Doherty, A. M. Endothelin: A New Challenge. J. Med. Chem. 1992, 35, 1493-1508. (b) Shiosaki, K. Recent Advances in Endothelin Receptor Antagonists. Exp. Opin. Ther. Pat. 1994, 4, 1361-1365. (c) Opgenorth, T. J. Endothelin Receptor Antagonism. Adv. Pharmacol. 1995, 33, 1-65. (d) Williams, D. L.; Walsh, T. F. Endothelin Blockade and Hypertension. In Antihypertensive Drugs; van Zwieten, P. A., Greenlee, W. J., Eds.; Harwood Academic: Amsterdam, 1997; pp 213-280. (e) Lago, M. A.; Luengo, J. I. Endothelin Antagonists. Annu. Rep. Med. Chem. 1996, 31, 81-90.
6. For recent reviews on the endothelin system, see: (a) Doherty, A. M. Endothelin: A New Challenge. J. Med. Chem. 1992, 35, 1493-1508. (b) Shiosaki, K. Recent Advances in Endothelin Receptor Antagonists. Exp. Opin. Ther. Pat. 1994, 4, 1361-1365. (c) Opgenorth, T. J. Endothelin Receptor Antagonism. Adv. Pharmacol. 1995, 33, 1-65. (d) Williams, D. L.; Walsh, T. F. Endothelin Blockade and Hypertension. In Antihypertensive Drugs; van Zwieten, P. A., Greenlee, W. J., Eds.; Harwood Academic: Amsterdam, 1997; pp 213-280. (e) Lago, M. A.; Luengo, J. I. Endothelin Antagonists. Annu. Rep. Med. Chem. 1996, 31, 81-90.
7. For recent reviews on the endothelin system, see: (a) Doherty, A. M. Endothelin: A New Challenge. J. Med. Chem. 1992, 35, 1493-1508. (b) Shiosaki, K. Recent Advances in Endothelin Receptor Antagonists. Exp. Opin. Ther. Pat. 1994, 4, 1361-1365. (c) Opgenorth, T. J. Endothelin Receptor Antagonism. Adv. Pharmacol. 1995, 33, 1-65. (d) Williams, D. L.; Walsh, T. F. Endothelin Blockade and Hypertension. In Antihypertensive Drugs; van Zwieten, P. A., Greenlee, W. J., Eds.; Harwood Academic: Amsterdam, 1997; pp 213-280. (e) Lago, M. A.; Luengo, J. I. Endothelin Antagonists. Annu. Rep. Med. Chem. 1996, 31, 81-90.
8. Rubanyi, G. M., Polokoff, M. A. Endothelins: Molecular Biology, Biochemistry, Pharmacology, Physiology, and Pathophysiology. Pharmacol. Rev. 1994, 46, 325-415.
9. Simonson, M. S. Endothelins: Multifunctional Renal Peptides. Physiol. Rev. 1993, 73, 375-411.
10. Haynes, W. G.; Webb, D. J. The Endothelin Family of Peptides: Local Hormones with Diverse Roles in Health and Disease? Clin. Sci. 1993, 84, 485-500.
11. Battistini, B.; Chailler, P.; D'Orléans-Juste, P.; Briére, N.; Sirois, P. Growth Regulatory Properties of Endothelins. Peptides 1993, 14, 385-399.
12. Arai, H.; Hori, S.; Aramori, I.; Ohkubo, H.; Nakanishi, S. Cloning and Expression of a cDNA Encoding an Endothelin Receptor. Nature 1990, 348, 730-732.
13. Sakurai, T.; Yanagisawa, M.; Takuwa, Y.; Miyazaki, H.; Kimura, S.; Goto, K.; Masaki, T. Cloning of a cDNA Encoding a Non-isopeptide-selective Subtype of the Endothelin Receptor. Nature 1990, 348, 732-735.
14. Warner, T. D.; Mitchell, J. A.; De Nucci, G.; Vane, J. R. Endothelin-1 and Endothelin-3 Release EDRF From Isolated Perfused Arterial Vessels of the Rat and Rabbit. J. Cardiovasc. Pharmacol. 1989, 13 (suppl. 5), S85-88.
15. Ishikawa, K.; Ihara, M.; Noguchi, K.; Mase, T.; Mino, N.; Saeki, T.; Fukuroda, T.; Fukami, T.; Ozaki, S.; Nagase, T.; Nishikibe, M.; Yano, M. Biochemical and Pharmacological Profile of a Potent and Selective EndothelinB-receptor Antagonist, BQ-788. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 4892-4896.
16. Vitola, J. V.; Forman, M. B.; Holsinger, J. P.; Kawana, M.; Atkinson, J. B.; Quertermous, T.; Jackson, E. K.; Murray, J. J. Role of Endothelin in a Rabbit Model of Acute Myocardial Infarction: Effects of Receptor Antagonists. J. Cardiovasc. Pharmacol. 1996, 28, 774-783.
17. Kiowski, W.; Sutsch, G.; Hunziker, P.; Muller, P.; Kim, J.; Oechslin, E.; Schmitt, R.; Jones, R.; Bertel, O. Evidence for Endothelin-1-mediated Vasoconstriction in Severe Chronic Heart Failure. Lancet 1995, 346, 732-736.
18. (a) Underwood, D. C.; Bochnowicz, S.; Osborn, R. R.; Luttmann, M. A.; Hay, D. W. Nonpeptide Endothelin Receptor Antagonists. X. Inhibition of Endothelin-1- and Hypoxia-induced Pulmonary Pressor Responses in the Guinea Pig by the Endothelin Receptor Antagonist, SB 217242. J. Pharmacol. Exp. Ther. 1997, 283, 1130-1137.
19. (b) Chen, S. J.; Chen, Y. F.; Opgenorth, T. J.; Wessale, J. L.; Meng, Q. C.; Durand, J.; DiCarlo, V. S.; Oparil, S. The Orally Active Nonpeptide Endothelin A-receptor Antagonist A-127722 Prevents and Reverses Hypoxia-induced Pulmonary Hypertension and Pulmonary Vascular Remodeling in Sprague-Dawley Rats. J. Cardiovasc. Pharmacol. 1997, 29, 713-725.
20. Zimmermann, M. Endothelin in Cerebral Vasospasm. Clinical and Experimental Results. J. Neurosurg. Sci. 1997, 41, 139-151.
21. A Receptor Blockade in a Rat Model of Radiocontrast-induced Nephropathy. Ren. Fail. 1997, 19, 753-761.
22. Burke, S. E.; Lubbers, N. L. ; Gagne, G. D.; Wessale, J. L.; Dayton, B. D.; Wegner, C. D.; Opgenorth, T. J. Selective Antagonism of the ET(A) Receptor Reduces Neointimal Hyperplasia After Balloon-induced Vascular Injury in Pigs. J. Cardiovasc. Pharmacol. 1997, 30, 33-41.
23. A Selective Endothelin Receptor Antagonists. 1. Discovery of A-127722. J. Med. Chem. 1996, 39, 1039-1048.
24. A Receptor Selectivity. Bioorg. Med. Chem. Lett., submitted.
25. Brooks, D. W.; Lu, L. D.-L.; Masamune, S. C-Acylation Under Virtually Neutral Conditions. Angew. Chem., Int. Ed. Engl. 1979, 18, 72-74.
26. Weiler, L. Alkylation of the Dianion of β-Keto Esters. J. Am. Chem. Soc. 1970, 92, 6702-6704.
27. Krapcho, A. P.; Diamani, J.; Cayen, C.; Bingham, R. 2-Carbethoxy Cyclooctanone. Organic Synthesis; John Wiley; New York, 1967; Vol. 47, p 20.
28. von Geldern, T. W.; Hoffman, D. J.; Kester, J. A.; Nellans, H. N.; Dayton, B. D.; Calzadilla, S. V.; Marsh, K. C.; Hernandez, L.; Chiou, W.; Dixon, D. B.; Wu-Wong, J. R.; Opgenorth, T. J. Azole Endothelin Antagonist. III. Using ΔlogP as a Tool to Improve Absorption. J. Med. Chem. 1996, 39, 982-991.
29. Roux, S.; Breu, V.; Giller, T.; Neidhart, W.; Ramuz, H.; Coassolo, P.; Clozel, J. P.; Clozel, M. Ro 61-1790, a New Hydrosoluble Endothelin Antagonist: General Pharmacology and Effects on Experimental Cerebral Vasospasm. J. Pharmacol. Exp. Ther. 1997, 283, 1110-1118.
30. A) Receptor-Selective Antagonists. J. Med. Chem. 1995, 38, 1259-1263.
31. A Antagonist 5-(Dimethyl-amino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide. J. Med. Chem. 1994, 37, 329-331.
32. A Receptor Antagonist. J. Pharmacol. Exp. Ther. 1995, 272, 1124-1134.
33. (a) Ohlstein, E. H.; Nambi, P.; Douglas, S. A; Edward R. M.; Gellai, M.; Lago, M. A.; Leber, J .D.; Cousins, R. D.; Gao, A.; Frazee, J. S.; Peishoff, C. E.; Bean, J. W.; Eggleston, D. S.; Elshourbagy, N. A.; Kumar, C.; Lee, J. A., Yu, T.-L.; Louden, C.; Brooks, D. P.; Weinstock, J.; Feuerstein, G.; Poste, G.; Ruffolo, R. R., Jr.; Gleason, J. G.; Elliott, J. D. SB 209670, a Rationally Designed Potent Nonpeptide Endothelin Receptor Antagonist. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 8052-8056.
34. (b) Ohlstein, E. H.; Nambi, P.; Lago, A.; Hay, D. W. P.; Beck, G.; Fong, K.-L.; Eddy, E. P.; Smith, P.; Ellens, H.; Elliott, J. D. Nonpeptide Endothelin Receptor Antagonists. VI: Pharmacological Characterization of SB 217242, A Potent and Highly Bioavailable Endothelin Receptor Antagonist. J. Pharmacol. Exp. Ther. 1996, 276, 609-615.
35. Wu, C.; Chan, M. F.; Stavros, F.; Raju, B.; Okun, I.; Mong, S.; Keller, K. M.; Brock, T.; Kogan, T. P.; Dixon, R. A. F. Discovery of TBC11251, a Potent, Long Acting, Orally Active Endothelin Receptor-A Selective Antagonist. J. Med. Chem. 1997, 40, 1690-1697.
36. Berridge, M. J. ; Dowens, C. P.; Hanley, M. R. Lithium Amplifies Agonist Dependent Phosphatidylinositol Responses in Brain and Salivary Glands. Biochem. J. 1982, 206, 587-595.
37. Statistical Consultants, Inc. PCNONLiN and NONLIN84: Software for the Statistical Analysis of Nonlinear Models. Am. Stat. 1986, 40, 52.
38. Sedman, A. J.; Wagner, J. G. CSTRIP-A FORTRAN Computer Program for Obtaining Initial Polyexponential Estimates. J. Pharm. Sci. 1976, 65, 1006-1010.