Finerenone

Finerenone
Systematic (IUPAC) name

(4S)-4-(4-Cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide
Clinical data
Routes of administration	Oral
Legal status
Legal status	Investigational
Identifiers
CAS Number	1050477-31-0
ATC code	none
PubChem	CID 60150535
ChemSpider	28669387
UNII	DE2O63YV8R
KEGG	D10633
ChEMBL	CHEMBL2181927
Synonyms	BAY 94-8862
Chemical data
Formula	C₂₁H₂₂N₄O₃
Molar mass	378.42 g/mol
SMILES CCOc1c2c(c(cn1)C)NC(=C([C@H]2c3ccc(cc3OC)C#N)C(=O)N)C
InChI InChI=1S/C21H22N4O3/c1-5-28-21-18-17(14-7-6-13(9-22)8-15(14)27-4)16(20(23)26)12(3)25-19(18)11(2)10-24-21/h6-8,10,17,25H,5H2,1-4H3,(H2,23,26)/t17-/m1/s1 Key:BTBHLEZXCOBLCY-QGZVFWFLSA-N

Finerenone (INN, USAN) (developmental code name BAY-94-8862) is a non-steroidal antimineralocorticoid that is in phase III clinical trials for the treatment of chronic heart failure as of October 2015. It has less relative affinity to other steroid hormone receptors than currently available antimineralocorticoids such as eplerenone and spironolactone, which should result in fewer adverse effects like gynaecomastia, impotence, and low sex drive.^[1]^[2]

Pharmacology

Finerenone blocks mineralocorticoid receptors, which makes it a potassium-sparing diuretic.

This table compares inhibitory (blocking) concentrations (IC₅₀, unit: nM) of three antimineralocorticoids. Mineralocorticoid receptor inhibition is responsible for the desired action of the drugs, whereas inhibition of the other receptors potentially leads to side effects. Lower values mean stronger inhibition.^[1]

	Spironolactone	Eplerenone	Finerenone
Mineralocorticoid receptor	24	990	18
Glucocorticoid receptor	2400	22,000	>10,000
Androgen receptor	77	21,200	>10,000
Progesterone receptor	740	31,200	>10,000

The above-listed drugs have insignificant affinity for the estrogen receptor.

Chemistry

Unlike currently marketed antimineralocorticoids, finerenone is not a steroid but a dihydropyridine derivative.

Research

The drug is also being investigated in early trials for the treatment of diabetic nephropathy.^[3]

References

1 2 Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel Herbst 2015 (German)
↑ Pitt, B; Anker, S. D.; Böhm, M; Gheorghiade, M; Køber, L; Krum, H; Maggioni, A. P.; Ponikowski, P; Voors, A. A.; Zannad, F; Nowack, C; Kim, S. Y.; Pieper, A; Kimmeskamp-Kirschbaum, N; Filippatos, G (2015). "Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): A randomized study of finerenone vs. Eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease". European Journal of Heart Failure 17 (2): 224–32. doi:10.1002/ejhf.218. PMID 25678098.
↑ Bakris, G. L.; Agarwal, R; Chan, J. C.; Cooper, M. E.; Gansevoort, R. T.; Haller, H; Remuzzi, G; Rossing, P; Schmieder, R. E.; Nowack, C; Kolkhof, P; Joseph, A; Pieper, A; Kimmeskamp-Kirschbaum, N; Ruilope, L. M.; Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy (ARTS-DN) Study Group (2015). "Effect of Finerenone on Albuminuria in Patients with Diabetic Nephropathy: A Randomized Clinical Trial". JAMA 314 (9): 884–94. doi:10.1001/jama.2015.10081. PMID 26325557.

Mineralocorticoids and antimineralocorticoids (H02)

Mineralocorticoids	11-Deoxycorticosterone (desoxycortone) 11-Deoxycortisol (cortodoxone) Aldosterone Corticosterone Cortisol (hydrocortisone) Desoxycortone acetate Desoxycortone enanthate Fludrocortisone Fludrocortisone acetate

Antimineralocorticoids	Amlodipine Benidipine Canrenoate potassium (potassium canrenoate) Canrenoic acid Canrenone Drospirenone Eplerenone Felodipine Finerenone Gestodene Nifedipine Nimodipine Nitrendipine Progesterone Spironolactone

Synthesis modifiers	Acetoxolone Aminoglutethimide Carbenoxolone Enoxolone Ketoconazole Metyrapone Mitotane Trilostane

^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

Mineralocorticoid signaling

Receptor
(ligands)

Agonists	11-Deoxycorticosterone (desoxycortone) 11-Deoxycortisol (cortodoxone) 16α,18-Dihydroxy-11-deoxycorticosterone 17-Hydroxyaldosterone 18-Hydroxy-11-deoxycorticosterone 19-Norprogesterone Aldosterone Corticosterone Desoxycortone acetate Desoxycortone enanthate Desoxycortone glucoside Desoxycortone pivalate Hydrocortisone (cortisol) Fludrocortisone Fludrocortisone acetate Mometasone furoate Prednisolone Prednisone

Antagonists	3α-Hydroxytibolone 3β-Hydroxytibolone 6β-Hydroxy-7α-thiomethylspironolactone 7α-Thiomethylspironolactone 17-Hydroxyprogesterone Amlodipine Benidipine BR-4628 Canrenoate potassium (potassium canrenoate) Canrenoic acid Canrenone Dicirenone Drospirenone Eplerenone Esaxerenone Felodipine Finerenone Gestodene Guggulsterone Mespirenone Mexrenoate potassium Mexrenoic acid Mexrenone Nifedipine Nimodipine Nitrendipine Oxprenoic acid Oxprenoate potassium (RU-28318) PF-03882845 Pregnenolone Progesterone Prorenoate potassium Prorenoic acid (prorenoate) Prorenone RU-26752 SC-5233 SC-8109 SM-368229 Spirorenone Spironolactone Spiroxasone Tibolone

Enzyme

Modulators	See here instead (modulators of 20,22-desmolase, 17α-hydroxylase/17,20-lyase, 3β-HSD, 11β-HSD, 21-hydroxylase, 11β-hydroxylase, and 18-hydroxylase).

Others

Precursors	Cholesterol 22R-Hydroxycholesterol 20α,22R-Dihydroxycholesterol Pregnenolone Pregnenolone sulfate 17-Hydroxypregnenolone Progesterone 17-Hydroxyprogesterone 11-Deoxycorticosterone 18-Hydroxydeoxycorticosterone Corticosterone 18-Hydroxycorticosterone

Indirect	ACTH (corticotropin) CRH Plasma proteins (albumin, transcortin) Vasopressin

See also: Androgenics • Estrogenics • Glucocorticoids • Progestogenics

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