Finerenone Chemical Properties

Boiling point:

554.7±50.0 °C(Predicted)

Density 

1.29±0.1 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

DMF: 10 mg/ml DMSO: 3 mg/ml Ethanol: insol PBS (pH 7.2): insol

pka

14.76±0.40(Predicted)

form 

solid

color 

White to off-white

λmax

255 nm

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

InChIKey

BTBHLEZXCOBLCY-QGZVFWFLSA-N

SMILES

N1C2=C(C(OCC)=NC=C2C)[C@H](C2=CC=C(C#N)C=C2OC)C(C(N)=O)=C1C

Finerenone Usage And Synthesis

Description

Finerenone is a novel mineralocorticoid receptor antagonist that has the effect of delaying the progression of chronic kidney disease. Some people may be aware of two other mineralocorticoid receptor antagonists: the diuretic antihypertensive drug spironolactone, and eplerenone.Finerenone is their cognate derivative and is a third-generation mineralocorticoid receptor antagonist. So far, finerenone is the only nonsteroidal mineralocorticoid receptor antagonist to be FDA approved.  Finerenone was granted FDA approval on 9 July 2021, followed by the EMA approval on 11 March 2022.

Uses

Finerenone is the first non-steroidal selective mineralocorticoid receptor antagonist, which can be used for the treatment of diabetic nephropathy, chronic kidney disease and end-stage renal disease. It can reduce the proteinuria of patients and improve the glomerular filtration rate.

Indications

Finerenone is used for the treatment of adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). Finerenone's indication is to reduce the risk of sustained estimated glomerular filtration rate decline, end-stage renal disease, end-stage renal disease, cardiovascular death, non-fatal myocardial infarction, and risk of hospitalisation for heart failure.

brand name

Finerenone is sold under the brand name Kerendia and Firialta.

Biological Activity

Finerenone (FIN, BAY 94-8862) is a highly selective, orally active, nonsteroidal antagonist of mineralocorticoid receptor (MR) with IC50 of 18 nM. Finerenone has the potential to study cardio-renal diseases such as type 2 diabetes and chronic kidney disease.

Synthesis

Synthesis scheme of finerenone: Firstly, benzaldehyde 20.1 was condensed with acetoacetamide under Knoevenagel condensation conditions to give high yield of ketone 20.2 of undetermined structure.Meanwhile, pyridinyl chloride 20.3 was treated at high temperature with strong alkali conditions followed by treatment with strong acid at low temperature to give filterable pyridinone solid 20.4.
Addition of 20.2 to a heated isobutanol solution of 20.4 resulted in a condensation-cyclisation reaction to give the nitrogen-containing heterocyclic compound 20.5 in good yield. The conversion of the pyridone to the corresponding ether was achieved by treating the pyridone with 1,1,1-triethoxyethane under acidic conditions. Some of the synthetic methods for fenaridones were carried out by chromatographic separation of the racemate 20.6, while a recent patent reports a classical splitting using tartaric acid derived salts. In one example, 20.6 was reacted with p-toluoyl-d-tartaric acid in a mixture of ethanol and water to give the target enantiomer in 78% enantiomeric excess, which was purified to 99% enantiomeric excess by re-suspension in ethanol and water to ultimately give 20.7 in about 41% yield. Adjusting the pH in water and ethanol with sodium carbonate gave the free base of fenaridone (20) in 97% yield.

in vivo

Finerenone (BAY 94-8862) lowers albuminuria by >40% and significantly reduces systolic blood pressure (SBP) in Munich Wistar Fr?mter (MWF) rat.

Mode of action

Finerenone is a Nonsteroidal Mineralocorticoid-Receptor Antagonist. The mechanism of action of finerenone is as a Mineralocorticoid Receptor Antagonist. Finerenone inhibits the effects of mineralocorticoids like aldosterone and cortisol when the MR is overactivated, possibly reducing inflammation and fibrosis in the heart and kidney.

References

Kolkhof, P., Hartmann, E., Freyberger, A., et al.Effects of finerenone combined with empagliflozin in a model of hypertension-induced end-organ damage. Am. J. Nephrol. 52(8), 642-652 (2021).
DOI: 10.1159/000516213
Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes.