7413-36-7

Usage

Uses

Used in Pharmaceutical Industry:
Nifenalol is used as a beta-adrenergic antagonist for the treatment of cardiovascular diseases, such as hypertension, angina pectoris, and arrhythmias. Its application in this industry is due to its ability to reduce heart rate, lower blood pressure, and decrease the workload on the heart, thus providing relief from the symptoms of these conditions.
Additionally, nifenalol is used as an αor β-adrenergic blocking agent for developing treatments for cardiac failure, asthma, and glaucoma. The application reason is its effectiveness in managing the symptoms of these conditions by blocking the action of adrenaline and noradrenaline on the respective receptors, leading to improved patient outcomes and quality of life.

InChI:InChI=1/C11H16N2O3/c1-8(2)12-7-11(14)9-3-5-10(6-4-9)13(15)16/h3-6,8,11-12,14H,7H2,1-2H3

Upstream product

• 6388-74-5 p-Nitrophenyloxirane 
• 75-31-0 isopropylamine 
• 67-64-1 acetone 
• 1374003-53-8 (R)-2,2,2-trichloro-1-phenylethyl (R)-2-hydroxy-2-(4-nitrophenyl)ethylcarbamate 
• 1374003-18-5 (S)-((R)-1-phenyl-2,2,2-trichloroethyl) 2-(4-nitrophenyl)aziridine-1-carboxylate 
• 125653-67-0 (R)-(-)-2-bromo-1-(4-nitrophenyl)ethanol 
• 77977-74-3 (R)-(-)-1-(4-nitrophenyl)-1,2-ethanediol 
• 100-19-6 (4-nitrophenyl)ethanone 
• 99-81-0 4-Nitrophenacyl bromide 
• 6388-74-5 (2R)-2-(4-nitrophenyl)oxirane 

Downstream Products

• 22487-18-9 3-isopropyl-5-(4-nitro-phenyl)-oxazolidine 
• 41191-17-7 2-(Isopropyl-methyl-amino)-1-(4-nitro-phenyl)-ethanol 
• 41959-01-7 2-[(2-Hydroxy-ethyl)-isopropyl-amino]-1-(4-nitro-phenyl)-ethanol 
• 5302-36-3 (+)-Nifenalol 
• 5054-57-9 (-)-Nifenalol 
• 22487-18-9 (R)-3-isopropyl-5-(4-nitro-phenyl)-oxazolidine 
• 7662-24-0 1-(4-amino-phenyl)-2-isopropylamino-ethanol 

Relevant academic research and scientific papers

Preparing β-blocker (R)-Nifenalol based on enantioconvergent synthesis of (R)-p-nitrophenylglycols in continuous packed bed reactor with epoxide hydrolase

An engineered epoxide hydrolase from Vigna radiate (VrEH2M263N) shows near-perfect enantioconvergence in single enzyme mediated hydrolysis of racemic p-nitrostyrene oxide (pNSO). To explore industrial potential of the promising biocatalyst, we tried to immobilize the VrEH2 variant by covalently linking onto a commercially available amino resin ECR8405F. Then a 5-mL packed bed reactor filled with the immobilized VrEH2M263N was connected with macroporous resin NKA-11 for in situ product adsorption, and the product (R)-p-nitrophenyl glycol (pNPG) was harvested by methanol elution, with 91% isolated yield and 97% ee. The continuous reactor was operated stably for more than 100 h with a space time yield of 20 g?L?1?h?1. Subsequently, the β-blocker (R)-Nifenalol was prepared by chemically synthesized from (R)-pNPG, affording the product in an overall yield of 61.3% (1.5 g) and an enantiopurity of 99.9% ee after recrystallization.

Integration of multiple active sites on large-pore mesoporous silica for enantioselective tandem reactions

Facile construction of a multifunctional heterogeneous catalyst through the assembly of Au/carbene and chiral ruthenium/diamine dual complexes in large-pore mesoporous silica was developed. This enables an efficient one-pot hydration-asymmetric transfer hydrogenation enantioselective tandem reaction of haloalkynes, affording chiral halohydrins with up to 99% enantioselectivity. Combined multifunctionalities, such as substrate-promoted silanol-functionality, BF4? anion-bonding gold/carbene and covalent-bonding chiral ruthenium/diamine active centers, contributed cooperatively to the catalytic performance.

Effect of basic and acidic additives on the separation of some basic drug enantiomers on polysaccharide-based chiral columns with acetonitrile as mobile phase

The separation of enantiomers of 16 basic drugs was studied using polysaccharide-based chiral selectors and acetonitrile as mobile phase with emphasis on the role of basic and acidic additives on the separation and elution order of enantiomers. Out of the studied chiral selectors, amylose phenylcarbamate-based ones more often showed a chiral recognition ability compared to cellulose phenylcarbamate derivatives. An interesting effect was observed with formic acid as additive on enantiomer resolution and enantiomer elution order for some basic drugs. Thus, for instance, the enantioseparation of several β-blockers (atenolol, sotalol, toliprolol) improved not only by the addition of a more conventional basic additive to the mobile phase, but also by the addition of an acidic additive. Moreover, an opposite elution order of enantiomers was observed depending on the nature of the additive (basic or acidic) in the mobile phase.

One-Pot cascade hydration-asymmetric transfer hydrogenation as a practical strategy to construct chiral β-adrenergic receptor blockers

The facile construction of biologically active β-adrenergic receptor agonists/blockers and analogues is a great fundamental and practical challenge in medical chemistry. Herein, we report a hydration-asymmetric transfer hydrogenation cascade to realize the one-pot enantioselective transformation of aromatic haloalkynes into chiral aromatic halohydrins, which can be converted readily into chiral β-adrenergicreceptor blockers. Such a one-pot cascade process involves the Au-catalyzed hydration of aryl-substituted haloalkynes to aryl-substituted α-halomethyl ketones and the Ru-catalyzed asymmetric transfer hydrogenation of aryl-substituted α-halomethyl ketones to aryl-substituted 2-haloethanols. The significant benefits of this procedure are that it provides chiral aromatic halohydrins in high yields, with excellent enantioselectivities, and a wide variety of functional groups are tolerated under mild conditions. The study described herein offers a useful approach to construct chiral β-adrenergic blockers, which is an attractive practical organic transformation that is performed in a one-pot manner.

One-pot route to β-adrenergic blockers via enantioselective organocatalysed epoxidation of terminal alkenes as a key step

A convenient and environmentally attractive one-pot two-step process for the synthesis of β-adrenergic blockers via Shi's organocatalytic epoxidation of terminal alkenes and subsequent aminolysis reaction of epoxides with isopropylamine under mild reaction conditions has been developed. This journal is the Partner Organisations 2014.

Copper bis(oxazolines) as catalysts for stereoselective aziridination of styrenes with N-tosyloxycarbamates

A Cu(I)-catalyzed asymmetric aziridination of styrenes with a chiral N-tosyloxycarbamate has been developed. Double stereodifferentiation was observed and both the N-tosyloxycarbamate substituent and the bis(oxazoline) ligand have a significant effect on the yields and diastereoselectivities. The best results for the aziridination were obtained with electron-deficient styrenes. Subsequent ring-opening reactions of styrene-derived aziridines at the benzylic position were observed with various oxygen and nitrogen nucleophiles under Lewis acid catalysis affording the corresponding products with complete inversion of stereochemistry. The strategy was used to synthesize the β-blocker, (R)-nifenalol.

Asymmetric synthesis of β-adrenergic blockers through multistep one-pot transformations involving in situ chiral organocatalyst formation

Two birds one stone: A new atom-economical one-pot approach to enantioselective chiral drug synthesis, involving in situ multistep organocatalyst formation and the application of the reaction for multistep sequential synthesis of β-adrenergic blockers is disclosed (see scheme).

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.

ANTIHYPERTENSIVE THERAPY

A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.

Method for treating resistant hypertension

A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.