46905-83-3

Basic information

• Product Name: (R)-Bunitrolol
• Synonyms: (R)-Bunitrolol;Benzonitrile, 2-[(2R)-3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-;Benzonitrile, 2-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-, (R)-;2-[(R)-3-(tert-Butylamino)-2-hydroxypropoxy]benzonitrile
• CAS NO: 46905-83-3
• Molecular Formula: C14H20 N2 O2
• Molecular Weight: 0
• Mol File: 46905-83-3.mol
• Article Data: 11

Chemical Properties

• Appearance: /
• CAS DataBase Reference: (R)-Bunitrolol(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-Bunitrolol(46905-83-3)
• EPA Substance Registry System: (R)-Bunitrolol(46905-83-3)

Safety Data

• Hazardous Substances Data: 46905-83-3(Hazardous Substances Data)

Usage

General Description

(R)-Bunitrolol is a selective beta-adrenergic blocking agent that is commonly used as an antihypertensive and antiarrhythmic medication. It works by blocking the effects of adrenaline and noradrenaline on the beta receptors in the heart and blood vessels, leading to a decrease in heart rate and blood pressure. It is primarily used in the treatment of hypertension, angina pectoris, and cardiac arrhythmias. Additionally, it has been studied for its potential use in the treatment of anxiety and panic disorders. (R)-Bunitrolol has been found to be well-tolerated and effective in lowering blood pressure and controlling heart rhythm, making it a valuable option for patients with cardiovascular conditions.

Upstream product

• 29876-08-2 bunitrolol hydrochloride 
• 611-20-1 salicylonitrile 
• 97960-34-4 2-(prop-2'-enyloxy)benzonitrile 
• 850427-94-0 (R)-4-(2-cyanophenoxymethyl)-1,3,2-dioxathiolane-2,2-dioxide 
• 850427-88-2 (R)-4-(2-cyanophenoxymethyl)-1,3,2-dioxathiolane-2-oxide 
• 93744-18-4 (S)-(+)-3-(2-cyanophenoxy)-1,2-epoxypropane 
• 75-64-9 tert-butylamine 
• 38465-16-6 1,2-epoxy-3-(2-cyanophenyl)propane 
• 42864-99-3 (RS)-1-chloro-3-(2-cyanophenoxy)propan-2-ol 
• 93744-17-3 (R)-(-)-3-(2-cyanophenoxy)-1,2-epoxypropane 
• 56715-37-8 (2S)-1-(2-cyanophenoxy)-2,3-propanediol 

Relevant articles and documents

Solid-state properties of 1,2-epoxy-3-(2-cyanophenoxy)propane, a conglomerate-forming chiral drug precursor

Both enantiomers of 1,2-epoxy-3-(2-cyanophenoxy)propane 1a were obtained and converted into enantiomeric bunitrolol hydrochlorides 3 to confirm the configuration of the formers; racemic 1a undergoes spontaneous resolution upon crystallization and could be resolved into individual enantiomers by a preferential crystallization with low efficiency.

Efficient chemoenzymatic synthesis of (RS)-, (R)-, and (S)-bunitrolol

A new chemical and the first chemoenzymatic synthesis of β-adrenergic receptor blocking agent bunitrolol is reported in racemic (RS) and enantioenriched forms (R and S). The intermediates (R)- and (S)-1-chloro-3-(2- cyanophenoxy)propan-2-ol intermediates were synthesized from the corresponding racemic alcohol through enzymatic kinetic resolution. The commercial available lipases PS-C and CCL exhibited complementary enantioselectivity during transesterification of the racemic alcohol with vinyl acetate affording the (R)-alcohol along with (S)-acetate and the (S)-alcohol along with (R)-acetate, respectively, and represent an example of enzymatic switch for reversal of enantioselectivity. The effects of various reaction parameters, such as temperature, time, substrate and enzyme concentration, and reaction medium, on the activity and enantioselectivity were optimized. The (R)- and (S)-alcohols were converted into (S)-and and (R)-bunitrolol, respectively, by treatment with tert-butylamine. The (R)- and (S)-acetates, obtained enzymatically were deacetylated to the corresponding alcohol by chemical hydrolysis and further converted into (S)-and and (R)-bunitrolol by chemical means. This is the first chemoenzymatic synthesis of both of the enantiomers of the drug. (RS)-, (R)-, and (S)-Bunitrolol were also synthesized following the 'all chemical' routes from (RS)-, (R)-, and (S)-epichlorohydrin via the corresponding (RS)-, (S)-, and (R)-2-cyanoglycidyl ether and the (RS)-, (R)-, and (S)-1-chloro-3-(2- cyanophenoxy)propan-2-ol intermediates with improved overall yields and better enantiomeric excesses compared to the reported processes.

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.