119365-23-0

Basic information

• Product Name: (S,R,R,S)-Nebivolol
• Synonyms: (S,R,R,S)-Nebivolol;[2S-[2R*[S*[S*(R*)]]]]-α,α'-[IMinobis(Methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-Methanol;R 65260
• CAS NO: 119365-23-0
• Molecular Formula: C22H25F2NO4
• Molecular Weight: 405.4350064
• Product Categories: Aromatics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 119365-23-0.mol

Chemical Properties

• Appearance: /
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: (S,R,R,S)-Nebivolol(CAS DataBase Reference)
• NIST Chemistry Reference: (S,R,R,S)-Nebivolol(119365-23-0)
• EPA Substance Registry System: (S,R,R,S)-Nebivolol(119365-23-0)

Safety Data

• Hazardous Substances Data: 119365-23-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S,R,R,S)-Nebivolol is used as a β-adrenergic blocker for the treatment of cardiovascular diseases. It works by blocking the action of adrenaline on β-adrenergic receptors, leading to a decrease in heart rate and blood pressure. This effect is particularly beneficial for patients suffering from hypertension and other heart-related conditions.
Additionally, due to its specific stereochemistry, (S,R,R,S)-Nebivolol may exhibit unique pharmacological properties compared to other enantiomers of Nebivolol, potentially offering advantages in terms of efficacy, safety, or reduced side effects. Further research and clinical trials are needed to fully understand and exploit these potential benefits.

Upstream product

• 99200-09-6 nebivolol 
• 303176-42-3 (R)-2-amino-1-[(S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]ethanol 
• 303176-46-7 (R)-2-[(R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl-4-methylbenzenesulfonate 
• 797054-19-4 (S)-2-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-6-fluoro-2,3-dihydrochromen-4-one 
• 797054-18-3 (R)-2-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-6-fluoro-2,3-dihydrochromen-4-one 
• 371-41-5 4-Fluorophenol 
• 394-32-1 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one 
• 1180001-17-5 d-(S,R,R,R)-benzyl nebivolol hydrochloride 
• 1030385-17-1 (SRRR)-d-N-benzilnebivolol 
• 197706-50-6 6-fluoro-(2R)-2-[(2R)-2-oxiranyl]-3,4-dihydrobenzopyran 
• 129050-23-3 (2S)-6-fluoro-2-[(2S)-oxiran-2-yl]-3,4-dihydro-2H-chromene 
• 905454-41-3 2-amino-1-[6-fluoro-(2R)-3H,4H-2-chromenyl]-(1S)-ethan-1-ol 
• 1224567-85-4 l-(R,S,S,S)-benzyl nebivolol hydrochloride 
• 99199-60-7 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid 

Downstream Products

• 152520-56-4 nebivolol hydrochloride 
• 9920-09-6 α,α'-iminobis(methylene)bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] hydrochloride 
• 920299-33-8 (R)-1-((R)-6-Fluoro-chroman-2-yl)-2-[(S)-2-((R)-6-fluoro-chroman-2-yl)-2-hydroxy-ethylamino]-ethanol; hydrochloride 
• 169293-50-9 nebivolol hydrochloride 
• 152520-56-4 DL-nebivolol hydrochloride 

Relevant articles and documents

Synthesis of intermediate compound and [...] (by machine translation)

Synthesis of intermediate compounds [a] and [...]. [Solution] a [...], asymmetric epoxidation, sulfonyl halide in the presence of base catalyst by sulfonation, alkylation of amines, such as synthesized by a series of cross-coupling reaction. [Effect] [...] important from the viewpoint of pharmacological value, high efficiency, low cost, and which meets the requirements of industrial, optical isomers may be prepared [...] and develop a method, which is very economical in social benefit. [Drawing] no (by machine translation)

Preparation method and application of Smo inhibitor based on Nebivolol

The invention discloses a preparation method and an application of a Smo inhibitor based on Nebivolol. The structural formula of the Smo inhibitor is as shown in a formula (I). The invention further discloses a synthetic method and an application of the Smo inhibitor. According to the Smo inhibitor, a beta-receptor retardant Nebivolol with inhibitory activity for Smo proteins serves as a lead compound, and optimization reconstruction is implemented based on the beta-receptor retardant Nebivolol to obtain the Smo inhibitor with good inhibitory activity.

A process for the preparation of nebivolol and wherein the intermediate compound

The invention discloses a preparation method of nebivolol used for preparing medicines for treating hypertension of slight or medium degrees, and an intermediate compound. The preparation method comprises the following steps: taking 6-fluoro-2-(1-hydroxy-2-paratoluensulfonyl oxygroup-ethyl)-3,4-dihydrobenzopyrans as an initial raw material, introducing amino, then coupling with 6- fluoro-3,4-dihydro-2-epoxy ethyl-2H-1-benzopyran, and preparing (S,R,R,R) and (R,S,S,S)-nebivolol. Compared with a prior art, the preparation method has the advantages of novel design, simple operation and high yield, the usage of hazardous reagent such as ssodium azide and sodium hydride can be avoided, a column chromatography purifying method is avoided, so that the preparation method conforms to industrial production.

A NEW METHOD FOR PRODUCING NEBIVOLOL HYDROCHLORIDE OF HIGH PURITY

The invention relates to a process for producing Nebivolol hydrochloride, (formula I) comprising the steps of: provision of a protected Nebivolol hydrochloride of the general formula (II), with P being an amine protecting group, and hydrogenation of said protected Nebivolol hydrochloride yielding Nebivolol hydrochloride of the formula (I).

METHOD FOR PRODUCING NEBIVOLOL

The present invention relates to a method for producing racemic nebivolol represented by general formula (I) from the enantiomerically-pure compounds represented by formula (IVa) and (IVb); whereby racemic nebivolol is obtained through mixing enantiomerically-pure d-nebivolol and l-nebivolol which are synthesised independent of each other as enantiomerically-pure compounds through individual coupling of the 4 enantiomerically-pure key intermediates represented by formula (IIa-d) to the corresponding precursors represented by formula (IIIa-d); whereby d-nebivolol (Ia) is obtained through coupling (IIa) to (IIIb) or (IIb) to (IIIa) and l-nebivolol (Ib) is obtained through coupling (IIc) to (IIId) or (IId) to (IIIc), and PG in the intermediates represented by formula (IIa-d) is a hydrogen atom or an amine protection group, and X in the precursors represented by formula (IIIa-d) is a halogen atom, a hydroxyl group, an acyl group, an alkylsulfonyloxy group or an arylsulfonyloxy group, whereby intermediate (IIa) is formed from (IIIa), intermediate (IIb) is formed from (IIIb), intermediate (IIc) is formed from (IIIc), and intermediate (IId) is formed from (IIId), whereby the precursors represented by formula (IIIa) and (IIId) originate from the ketone precursor represented by formula (IVa), and the precursors represented by formula (IIIb) and (IIIc) originate from the ketone precursor represented by formula (IVb), and Z in the ketone precursors (IVa,b) is a halogen atom, a hydroxyl function, an acyl group, an alkylsulfonyloxy group or an arylsulfonyloxy group.

PREPARATION OF NEBIVOLOL

Processes for the synthesis of pharmacologically active 2,2-iminobisethanol derivatives, e.g., 2H-1-benzopyran-2 methanol-α,α′-iminobis(methylene)]bis-[6-fluoro-3,4-dihydro-[2R*[R*[R*(S*)]]]], and their pharmaceutically acceptable salts.

PROCESS FOR THE PREPARATION OF NEBIVOLOL

The present invention relates to a novel process for the synthesis of Nebivolol product represented in Scheme (1), comprised of a reduced number of high-yield steps, and characterized by the kinetic resolution of the two epoxide pairs diastereoisomeric therebetween (mixture 1), allowing to avoid complex chromatographic separations.

PROCESS FOR PREPARING NEBIVOLOL

The present invention relates to a process for preparing Nebivolol and, more particularly, to an improved method of debenzylation of a compound of formula (II) useful for preparing nebivolol endowed with high purity.

Chiral separations of some β-adrenergic agonists and antagonists on AmyCoat column by HPLC

Sixteen β-adrenergic antagonists namely acebutalol, alprenolol, atenolol, bisoprolol, bopindolol, bufurolol, carazolol, celiprolol, indenolol, metaprolol, nebivolol, oxprenolol, practolol, propranolol, tertalol, and timolol, and two β-adrenergic agonists namely cimeterol and clenbuterol were resolved on AmyCoat (150 x 46 mm, 3 μm size of silica particle) by using (85:15:0.1, v/v/v), (90:10:0.1, v/v/v), and (95:05:0.1, v/v/v) combinations of η-heptane, ethanol, and diethylamine solvents, respectively. The flow rates used were 0.5, 1.0, 2.0, and 3.0 ml/min with detection at 225 nm. The values of capacity, separation, and resolution factors ranged from 0.38 to 19.70, 1.08-2.33, and 1.0 and 4.50, respectively. The maximum and minimum resolutions were achieved for celiprolol and bufurolol, respectively. The chiral recognition mechanisms were also discussed. The values of validation parameters were calculated.

THERAPY FOR COMPLICATIONS OF DIABETES

A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.