83073-79-4

Basic information

• Product Name: (±)-Bunitrolol
• CAS NO: 83073-79-4
• Molecular Weight: 0
• Mol File: 83073-79-4.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: (±)-Bunitrolol(CAS DataBase Reference)
• NIST Chemistry Reference: (±)-Bunitrolol(83073-79-4)
• EPA Substance Registry System: (±)-Bunitrolol(83073-79-4)

Safety Data

• Hazardous Substances Data: 83073-79-4(Hazardous Substances Data)

Upstream product

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

Relevant articles and documents

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.

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.

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.

Spontaneous resolution amongst chiral ortho-cyanophenyl glycerol derivatives: an effective preferential crystallization approach to a single enantiomer of the β-adrenoblocker bunitrolol

The β-adrenoblocker bunitrolol 1 as well as intermediate cyclic sulfate 6 and glycidyl ether 8 have been prepared in enantiopure form by starting from enantiopure o-cyanophenyl glycerol ether 2 by an entrainment resolution procedure. Thermal investigations reveal that 1·HCl forms a moderately stable racemic compound, whereas 2, 6 and 8 are conglomerate forming substances potentially capable of entrainment resolution. Some chemical and chiroptical characteristics for bunitrolol and possible intermediates in its synthesis were corrected, and configurations were verified with the configuration of 1·HCl.

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.

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.

Asymmetric synthesis of aryloxypropanolamines via OsO4-catalyzed asymmetric dihydroxylation

A simple and effective procedure for the enantioselective synthesis of several β-adrenergic blocking agents incorporating the first asymmetric synthesis of celiprolol, is described. The key steps are (i) sharpless asymmetric dihydroxylation of aryl allyl ethers to introduce chirality into the molecules and (ii) conversion of cyclic sulfates into the corresponding epoxides using a three-step procedure.

Retard form of pharmaceuticals with insoluble porous diffusion coatings

A pharmaceutical dosage unit retard form having a constant, pH-independent release rate of active ingredient, consisting of a core comprising an active ingredient, and a semi-permeable diffusion coating over the core, were the coating consists of a water-insoluble film-former, a water-soluble polymer and eventually an acid-insoluble polymer incorporated therein.

Enteric coated mixture of 4-(2-hydroxy-3-isopropylamino-propoxy) indole and sodium lauryl sulphate

The present invention provides a pharmaceutical composition for controlled release of 4-(2-hydroxy-3-isopropylamino-propoxy) indole in the intestinal tract, admixed with sodium lauryl sulphate, and enteric coated.