1050477-31-0

Basic information

• Product Name: Finerenone (BAY 94-8862)
• Synonyms: Finerenone (BAY 94-8862)
• CAS NO: 1050477-31-0
• Molecular Formula: C₂₁H₂₂N₄O₃
• Molecular Weight: 378.42438
• Mol File: 1050477-31-0.mol

Chemical Properties

• Boiling Point: 554.7±50.0 °C(Predicted)
• Appearance: /
• Density: 1.29±0.1 g/cm3(Predicted)
• PKA: 14.76±0.40(Predicted)
• CAS DataBase Reference: Finerenone (BAY 94-8862)(CAS DataBase Reference)
• NIST Chemistry Reference: Finerenone (BAY 94-8862)(1050477-31-0)
• EPA Substance Registry System: Finerenone (BAY 94-8862)(1050477-31-0)

Safety Data

• Hazardous Substances Data: 1050477-31-0(Hazardous Substances Data)

Usage

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.

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.

In vivo

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

Upstream product

• 1050477-27-4 4(R,S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 
• 1050477-43-4 2-cyanoethyl 4-(4-cyano-2-methoxyphenyl)-2,8-dimethyl-5-oxo-1,4,5,6-tetrahydro-l,6-naphthyridine-3-carboxylate 
• 1050477-44-5 2-cyanoethyl 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 
• 1050477-45-6 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 
• 95306-64-2 4-amino-5-methylpyridine-2(1H)-one 
• 5977-14-0 acetoacetamido 
• 1666-28-0 4-bromosalicylic acid 
• 21962-45-8 4-formyl-3-methoxy-benzonitrile 
• 43192-33-2 4-bromo-2-methoxybenzaldehyde 

Relevant articles and documents

Synthetic method of fenerenone and intermediate thereof

The invention provides a novel synthetic method of a fenerenone intermediate. The method comprises the following steps: (1) in the presence of an acid and in an inert solvent or solvent-free condition, carrying out a reaction on diethyl malonate, 4-cyano-2-methoxybenzaldehyde and 4-amino-5-methyl-2-hydroxypyridine to prepare a compound 1; (2) carrying out alkylation reaction on the compound 1 obtained in the step (1) and triethyl orthoformate in an inert solvent or solvent-free condition under acid catalysis to obtain a compound 2; (3) reducing the compound 2 obtained in the step (2) through a reducing agent to obtain a compound 3; (4) in the presence of a catalyst, splitting the compound 3 and alcohol by a chemical method to prepare a chiral compound 4; the reaction formula is shown in the specification. By applying the technical scheme provided by the invention, a chiral column splitting method is avoided, so that the cost is reduced; by adopting a chemical method for splitting, the raw material loss is reduced, the post-treatment is simple, and the industrial large-scale production is facilitated.

PROCESS FOR PREPARING (4S)-4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-2,8-DIMETHYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINE-3-CARBOXAMIDE ENABLED BY A CATALYTIC ASYMMETRIC HANTZSCH ESTER REDUCTION

The present invention relates to a novel process for preparing (4S)-4-(4-Cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide by an asymmetric Hantzsch ester reduction of racemic 4-(4-Cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,6-naphthyridine-3-carboxamide.

METHOD FOR THE PREPARATION OF (4S)-4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-2,8-DIMETHYL-1,4-DIHYDRO-1-6-NAPHTHYRIDINE-3-CARBOX-AMIDE BY RACEMATE SEPARATION BY MEANS OF DIASTEREOMERIC TARTARIC ACID ESTERS

The present invention relates to a novel and improved process for preparing (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (I) and also to the preparation of the enantiomer (Ia) by racemat

Enantioselective Total Synthesis of (?)-Finerenone Using Asymmetric Transfer Hydrogenation

(?)-Finerenone is a nonsteroidal mineralocorticoid receptor antagonist currently in phase III clinical trials for the treatment of chronic kidney disease in type 2 diabetes. It contains an unusual dihydronaphthyridine core. We report a 6-step synthesis of (?)-finerenone, which features an enantioselective partial transfer hydrogenation of a naphthyridine using a chiral phosphoric acid catalyst with a Hantzsch ester. The process is complicated by the fact that the naphthyridine exists as a mixture of two atropisomers that react at different rates and with different selectivities. The intrinsic kinetic resolution was converted into a kinetic dynamic resolution at elevated temperature, which enabled us to obtain (?)-finerenone in both high yield and high enantioselectivity. DFT calculations have revealed the origin of selectivity.

METHOD FOR THE PREPARATION OF (4S)-4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-2,8-DIMETHYL-1,4-DIHYDRO-1-6-NAPHTHYRIDINE-3-CARBOXAMIDE AND RECOVERY OF (4S)-4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-2,8-DIMETHYL-1,4-DIHYDRO-1-6-NAPHTHYRIDINE-3-CARBOXAMIDE BY ELECTROCHEMICAL METHODS

The present invention relates to a novel process for preparing (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (I) and recovering (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (I) proceeding from (4R)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula ent-(I)

METHOD FOR THE PREPARATION OF (4S)-4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-2,8-DIMETHYL-1,4-DIHYDRO-1-6-NAPHTHYRIDINE-3-CARBOXAMIDE AND THE PURIFICATION THEREOF FOR USE AS AN ACTIVE PHARMACEUTICAL INGREDIENT

The present invention relates to a novel and improved process for preparing (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (I)

METHOD FOR THE PREPARATION OF (4S)-4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-2,8-DIMETHYL-1,4-DIHYDRO-1-6-NAPHTHYRIDINE-3-CARBOX-AMIDE AND THE PURIFICATION THEREOF FOR USE AS AN ACTIVE PHARMACEUTICAL INGREDIENT

The present invention relates to a novel and improved process for preparing (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (I) and also the preparation and use of the crystalline polymorph I of (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (I).

SUBSTITUTED 4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINAMIDES AND USE THEREOF

1,6-Naphthyridine or 8-azaquinazoline derivatives (I) are new. 1,6-Naphthyridine or 8-azaquinazoline derivatives of formula (I) are new. D : N or CR 4>; R 4> : H, F, CF 3 or 1-4C alkyl; Ar : 5-R 5>-6-R 6>-2-methyl-4-oxo-4H-1-benzopyran-8-yl; 3-R 6>-4-R 8>-1-naphthyl optionally substituted with 1-3 of R 7>; 7-R 6>-8-R 8>-5-quinolinyl optionally substituted with 1-2 of R 7>; or 2-R 9>-3-R 10>-4-R 8>-5-R 6>-phenyl; R 5> : H, F, Cl, CN, NO 2, CF 3 or 1-4C alkyl; R 6> : H or F; R 7> : halo, 1-4C alkyl, CF 3, 1-4C alkoxy or OCF 3; R 8> : CN or NO 2; R 9> : H or halo; optionally fluorinated 1-4C alkyl, 1-4C alkoxy, 1-4C alkylthio of di(1-4C alkyl)amino; or phenyl optionally substituted with halo, 1-4C alkyl or CF 3; R 10> : H, halo or 1-4C alkyl; R 1> : optionally fluorinated 1-4C alkyl; R 2> : 1-6C alkyl optionally substituted with 3-7C cycloalkyl or F; or SO 2R 11>; R 11> : 1-6C alkyl, CF 3 or 3-7C cycloalkyl; or phenyl or heteroaryl optionally substituted with 1-2 of halo, CN, 1-4C alkyl, CF 3, 1-4C alkoxy and/or OCF 3; R 3> : H, F, CF 3 or 1-4C alkyl. An independent claim is also included for a process for preparing (I). [Image] ACTIVITY : Hypotensive; Cardiant; Hepatotropic; Nephrotropic; Cerebroprotective. MECHANISM OF ACTION : Mineralocorticoid receptor (MR) antagonist. 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2-methyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide had an IC 50 of 35 nM when tested on cells expressing a GAL4-MR chimera.