Advances in the Development of Non-steroidal Mineralocorticoid-receptor Antagonists

  1. Rodríguez, Yoel
  2. L. Pérez-Gordillo, Felipe
  3. Jesús Pérez de Vega, Maria
  4. Gerona-Navarro, Guillermo
  5. González-Muñiz, Rosario
  6. Alvarez de la Rosa, Diego
  7. Martín-Martínez, Mercedes
Book:
Aldosterone-Mineralocorticoid Receptor. Cell Biology to Translational Medicine

ISBN: 978-1-83962-200-7

Year of publication: 2019

Type: Book chapter

Export: RIS
DOI: 10.5772/intechopen.88417 GOOGLE SCHOLAR lock_openOpen access editor
Author's full text: lockOpen access editor

Bibliographic References

  • Rossier BC, Baker ME, Studer RA. Epithelial sodium transport and its control by aldosterone: The story of our internal environment revisited. Physiological Reviews. 2015;95:297-340
  • Chapman K, Holmes M, Seckl J. 11beta-hydroxysteroid dehydrogenases: Intracellular gate-keepers of tissue glucocorticoid action. Physiological Reviews. 2013;93:1139-1206
  • Gomez-Sanchez E, Gomez-Sanchez CE. The multifaceted mineralocorticoid receptor. Comprehensive Physiology. 2014;4:965-994
  • Gomez-Sanchez EP. Third-generation mineralocorticoid receptor antagonists: Why do we need a fourth? Journal of Cardiovascular Pharmacology. 2016;67:26-38
  • Jaisser F, Farman N. Emerging roles of the mineralocorticoid receptor in pathology: Toward new paradigms in clinical pharmacology. Pharmacological Reviews. 2016;68:49-75
  • Young MJ, Rickard AJ. Mechanisms of mineralocorticoid salt-induced hypertension and cardiac fibrosis. Molecular and Cellular Endocrinology. 2012;350:248-255
  • Herrada AA et al. Aldosterone as a modulator of immunity: Implications in the organ damage. Journal of Hypertension. 2011;29:1684-1692
  • Queisser N, Schupp N. Aldosterone, oxidative stress, and NF-kappaB activation in hypertension-related cardiovascular and renal diseases. Free Radical Biology & Medicine. 2012;53:314-327
  • Bauersachs J, Jaisser F, Toto R. Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension. 2015;65:257-263
  • Kolkhof P et al. Steroidal and novel non-steroidal mineralocorticoid receptor antagonists in heart failure and cardiorenal diseases: Comparison at bench and bedside. Handbook of Experimental Pharmacology. 2017;243:271-305
  • Infante M, Armani A, Mammi C, Fabbri A, Caprio M. Impact of adrenal steroids on regulation of adipose tissue. Comprehensive Physiology. 2017;7:1425-1447
  • Daruich A et al. Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis. Progress in Retinal and Eye Research. 2015;48:82-118
  • Brown R, Quirk J, Kirkpatrick P. Eplerenone. Nature Reviews. Drug Discovery. 2003;2:177-178
  • Alvarez de la Rosa D, Navarro-Gonzalez JF, Giraldez T. ENaC modulators and renal disease. Current Molecular Pharmacology. 2013;6:35-43
  • Roscioni SS, de Zeeuw D, Bakker SJ, Lambers Heerspink HJ. Management of hyperkalaemia consequent to mineralocorticoid-receptor antagonist therapy. Nature Reviews. Nephrology. 2012;8:691-699
  • Martin-Martinez M et al. Modulating mineralocorticoid receptor with non-steroidal antagonists. New opportunities for the development of potent and selective ligands without off-target side effects. Journal of Medicinal Chemistry. 2017;60:2629-2650
  • Arhancet GB et al. Stereochemical requirements for the mineralocorticoid receptor antagonist activity of dihydropyridines. Journal of Medicinal Chemistry. 2010;53:4300-4304
  • Bärfacker L et al. Discovery of BAY 94-8862: A nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem. 2012;7:1385-1403
  • Arhancet GB et al. Discovery of novel cyanodihydropyridines as potent mineralocorticoid receptor antagonists. Journal of Medicinal Chemistry. 2010;53:5970-5978
  • Fagart J et al. A new mode of mineralocorticoid receptor antagonism by a potent and selective nonsteroidal molecule. The Journal of Biological Chemistry. 2010;285:29932-29940
  • Fagart J et al. Antagonism in the human mineralocorticoid receptor. The EMBO Journal. 1998;17:3317-3325
  • Brandish P, Fraley E, Mark E, Hershey JC, Steen JT. Mineralocorticoid receptor modulators. 2009. WO2009/078934A1
  • Arai K et al. Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist. European Journal of Pharmacology. 2015;761:226-234
  • Casimiro-Garcia A et al. Identification of (R)-6-(1-(4-Cyano-3-methylphenyl)-5-cyclopentyl-4,5-dihydro-1H-pyrazol-3-yl)-2-methoxynicotinic acid, a highly potent and selective nonsteroidal mineralocorticoid receptor antagonist. Journal of Medicinal Chemistry. 2014;57:4273-4288
  • Meyers MJ et al. Discovery of (3S,3aR)-2-(3-Chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy. Journal of Medicinal Chemistry. 2010;53:5979-6002
  • Cox JM et al. Mineralocorticoid receptor antagonists: Identification of heterocyclic amide replacements in the oxazolidinedione series. Bioorganic & Medicinal Chemistry Letters. 2014;24:1681-1684
  • Michellys PY, Pei W, Petrassi HM, Richmond W. Compounds and compositions as modulators of steroid hormone nuclear receptors. 2006. WO2006/015259
  • Hasui T et al. Identification of benzoxazin-3-one derivatives as novel, potent, and selective nonsteroidal mineralocorticoid receptor antagonists. Journal of Medicinal Chemistry. 2011;54:8616-8631
  • Hasui T et al. Design, synthesis, and structure–activity relationships of dihydrofuran-2-one and dihydropyrrol-2-one derivatives as novel benzoxazin-3-one-based mineralocorticoid receptor antagonists. Bioorganic & Medicinal Chemistry. 2013;21:5983-5994
  • Granberg KL et al. Identification of mineralocorticoid receptor modulators with low impact on electrolyte homeostasis but maintained organ protection. Journal of Medicinal Chemistry. 2019;62:1385-1406
  • Neel DA et al. 3,3-Bisaryloxindoles as mineralocorticoid receptor antagonists. Bioorganic & Medicinal Chemistry Letters. 2005;15:2553-2557
  • Bell MG et al. (S)-N-{3-[1-Cyclopropyl-1-(2,4-difluoro-phenyl)-ethyl]-1H-indol-7-yl}-methanesulfonamide: A potent, nonsteroidal, functional antagonist of the mineralocorticoid receptor. Journal of Medicinal Chemistry. 2007;50:6443-6445
  • Cernak TA, Dykstra KD. Mineralocorticoid receptor antagonists. 2014. WO2014/014794A2
  • Katayama S, Hori S, Hasegawa F, Suzuki K. Biaryl amide derivative or pharmaceutically acceptable salt thereof. 2013. US2013/116227A1
  • Boyer S, Guo X, Wu D, Wu F. Pyridyl ureas as mineralocorticoid receptor antagonists. 2012. WO2012/064631A1
  • Nordqvist A et al. Structure-based drug design of mineralocorticoid receptor antagonists to explore oxosteroid receptor selectivity. ChemMedChem. 2017;12:50-65
  • Kowala MC. Combination therapy for resistant hypertension. 2015. WO2015/130568
  • http://www.chemspider.com/Chemical-Structure.29361352.html [Accessed: July 27, 2018]
  • https://www.chemicalregister.com/LY2623091/Suppliers/pid705106.htm [Accessed: July 27, 2018]
  • Lotesta SD et al. Identification of spirooxindole and dibenzoxazepine motifs as potent mineralocorticoid receptor antagonists. Bioorganic and Medicinal Chemistry. 2016;24:1384-1391
  • Kolkhof P, Nowack C, Eitner F. Nonsteroidal antagonists of the mineralocorticoid receptor. Current Opinion in Nephrology and Hypertension. 2015;24:417-424
  • The Practice of Medicinal Chemistry. 3rd ed. Academic Press; 2008
  • Clinical Trials Information. Available from: https://clinicaltrials.gov/ [Accessed: July 27, 2018]
  • Wang EB, Chaudhary A, Waterhouse TH, Dickinson GL. Population pharmacokinetics of LY2623091 in patients with hypertension and chronic kidney disease. Journal of Clinical Pharmacology. 2017;57:739-746
  • Dickinson GL, Phillips DL, Posada MM, Chaudhary A, Hall SD. Physiologically based pharmacokinetic modeling to understand the observed drug-drug interaction of LY2623091 with CYP3A inhibitors itraconazole and diltiazem. International Journal of Pharmacokinetics. 2017;2:233-245
  • Clinical Trial Information. Available from: https://clinicaltrials.gov/ct2/results?cond=&term=LY2623091 [Accessed: July 27, 2018]
  • https://adisinsight.springer.com/drugs/800033156 [Accessed: July 27, 2018]
  • https://ncats.nih.gov/files/PF-03882845.pdf [Accessed: July 27, 2018]
  • https://clinicaltrials.gov/ct2/show/NCT01488877 [Accessed: July 27, 2018]
  • Bamberg K et al. Preclinical pharmacology of AZD9977: A novel mineralocorticoid receptor modulator separating organ protection from effects on electrolyte excretion. PLoS One. 2018;13:e0193380
  • Erlandsson F et al. Clinical safety, tolerability, pharmacokinetics and effects on urinary electrolyte excretion of AZD9977, a novel, selective mineralocorticoid receptor modulator. British Journal of Clinical Pharmacology. 2018;84:1486-1493
  • Clinical Trials Information. Available from: https://www.clinicaltrials.gov/ct2/results?cond=&term=azd9977 [Accessed: July 27, 2018]
  • Clinical Trials Information. Available from: https://www.clinicaltrials.gov/ct2/results?cond=&term=kbp5074 [Accessed: July 27, 2018]
  • IIijima TY, Akatsuka H, Kawaguchi T. Benzoxazines and related nitrogen-containing heterobicyclic compounds useful as mineralocorticoid receptor modulating agents. 2007. WO2007/089034
  • Clinical Trials Information. Available from: https://www.clinicaltrials.gov/ct2/results?term=MT3995 [Accessed: July 27, 2018]
  • Amazit L et al. Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator-1. The Journal of Biological Chemistry. 2015;290:21876-21889
  • Grune J et al. Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone's antifibrotic activity. Hypertension. 2018;71:599-608
  • Kolkhof P et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. Journal of Cardiovascular Pharmacology. 2014;64:69-78
  • Pitt B et al. Rationale and design of ARTS: A randomized, double-blind study of BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease. European Journal of Heart Failure. 2012;14:668-675
  • Pitt B et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: A randomized, double-blind trial. European Heart Journal. 2013;34:2453-2463
  • Haller H, Bertram A, Stahl K, Menne J. Finerenone: A new mineralocorticoid receptor antagonist without hyperkalemia: An opportunity in patients with CKD? Current Hypertension Reports. 2016;18:1-9
  • Heinig R, Kimmeskamp-Kirschbaum N, Halabi A, Lentini S. Pharmacokinetics of the novel nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94-8862) in individuals with renal impairment. Clinical Pharmacology in Drug Development. 2016;5:488-501
  • Bakris GL et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: A randomized clinical trial. JAMA, the Journal of the American Medical Association. 2015;314:884-894
  • Bramlage P et al. Non-steroidal mineralocorticoid receptor antagonism for the treatment of cardiovascular and renal disease. European Journal of Heart Failure. 2016;18:28-37
  • Filippatos G et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. European Heart Journal. 2016;37:2105-2114
  • Lachaux M et al. Short- and long-term administration of the non-steroidal mineralocorticoid receptor antagonist finerenone opposes metabolic syndrome-related cardio-renal dysfunction. Diabetes, Obesity & Metabolism. 2018. p. 1-9
  • Bender SB et al. Mineralocorticoid receptor antagonism treats obesity-associated cardiac diastolic dysfunction. Hypertension. 2015;65:1082-1088
  • Clinical Trials Information. Available from: https://www.clinicaltrials.gov/ct2/results?term=finerenone [Accessed: July 27, 2018]
  • Arai K, Tsuruoka H, Homma T. CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist, prevents hypertension and cardiorenal injury in Dahl salt-sensitive hypertensive rats. European Journal of Pharmacology. 2015;769:266-273
  • Arai K, Morikawa Y, Ubukata N, Tsuruoka H, Homma T. CS-3150, a novel nonsteroidal mineralocorticoid receptor antagonist, shows preventive and therapeutic effects on renal injury in deoxycorticosterone acetate/salt-induced hypertensive rats. The Journal of Pharmacology and Experimental Therapeutics. 2016;358:548-557
  • https://www.businesswire.com/news/home/20180226006626/en/Exelixis-Announces-Collaborator-Daiichi-Sankyo%E2%80%99s-Submission-Regulatory [Accessed: July 27, 2018]
  • Clinical Trials Information. Available from: https://www.clinicaltrials.gov/ct2/results?term=cs3150 [Accessed: July 27, 2018]
  • Hasui T et al. Discovery of 6-[5-(4-fluorophenyl)-3-methyl-pyrazol-4-yl]-benzoxazin-3-one derivatives as novel selective nonsteroidal mineralocorticoid receptor antagonists. Bioorganic & Medicinal Chemistry. 2014;22:5428-5445
  • Bledsoe RK et al. A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor. The Journal of Biological Chemistry. 2005;280:31283-31293
  • Pymol Molecular Graphics System, Version 1.7 Schrödinger, LLC