6452-71-7

Hazards Identification

Pictogram(s):

Signal:

Danger

GHS Hazard Statements:

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]
H311 (100%): Toxic in contact with skin [Danger Acute toxicity, dermal]
H331 (100%): Toxic if inhaled [Danger Acute toxicity, inhalation]

Precautionary Statement Codes:

P261, P264, P270, P271, P280, P301+P316, P302+P352, P304+P340, P316, P321, P330, P361+P364, P403+P233, P405, and P501

Hazard Classes and Categories:

Acute Tox. 3 (100%)

Hazards Summary:

Allergic contact dermatitis reported in a pharmaceutical worker; [Kanerva, p. 1822] See Propranolol.

Usage

Uses

Used in Pharmaceutical Industry:
Oxprenolol is used as a vasodilator, specifically for coronary applications, to improve blood flow and reduce the workload on the heart. It is particularly effective in treating angina, hypertension, and certain arrhythmias by selectively blocking β1-adrenergic receptors and decreasing heart rate and contractility.

Therapeutic Function

Antiarrhythmic

Contact allergens

The beta-blocker oxprenolol induced contact dermatitis in a worker at a pharmaceutical plant, in a division for drug synthesis. Epichlorhydrin was also used for the production of drugs propranolol and oxprenolol.

InChI:InChI=1S/C15H23NO3/c1-4-9-18-14-7-5-6-8-15(14)19-11-13(17)10-16-12(2)3/h4-8,12-13,16-17H,1,9-11H2,2-3H3

Upstream product

• 6452-74-0 3-(o-Allyloxyphenoxy)-2-hydroxy-1-chlorpropan 
• 75-31-0 isopropylamine 
• 5741-15-1 BA 42154 
• 106-95-6 allyl bromide 
• 144106-10-5 O-propionyloxprenolol 
• 144106-09-2 O-acetyloxprenolol 
• 144106-13-8 O-pivaloyloxprenolol 
• 144106-11-6 O-butyryloxprenolol 
• 144106-12-7 O-valeryloxprenolol 
• 6452-72-8 1-(2-allyloxyphenoxy)-2,3-epoxypropane 
• 1126-20-1 2-allyloxyphenol 

Downstream Products

• 53564-65-1 2-(2-allyloxyphenoxy)acetic acid 
• 6452-54-6 3--1,2-propanediol 
• 6452-71-7 1-[2-(allyloxy)phenoxy]-3-(isopropylamino)propan-2-ol 
• 6452-71-7 (-)-Oxprenolol 
• 5741-15-1 BA 42154 
• 848355-06-6 (RS)-1-[Allyl(isopropyl)amino]-3-{2-(allyloxy)phenoxy}propan-2-ol 
• 66901-82-4 (R)-2-allyloxy-1-(2,3-dihydroxypropoxy)benzene 
• 71186-74-8 2-(3-isopropyl-2-phenyl-oxazolidin-5-ylmethoxy)-phenol 
• 848355-16-8 (RS)-2-[Allyl(isopropyl)amino]-1-{[2-(allyloxy)phenoxy]methyl}ethylacetat 

Relevant academic research and scientific papers

Enantioselective potential of polysaccharide-based chiral stationary phases in supercritical fluid chromatography

The enantioselective potential of two polysaccharide-based chiral stationary phases for analysis of chiral structurally diverse biologically active compounds was evaluated in supercritical fluid chromatography using a set of 52 analytes. The chiral selectors immobilized on 2.5?μm silica particles were tris-(3,5-dimethylphenylcarmabate) derivatives of cellulose or amylose. The influence of the polysaccharide backbone, different organic modifiers, and different mobile phase additives on retention and enantioseparation was monitored. Conditions for fast baseline enantioseparation were found for the majority of the compounds. The success rate of baseline and partial enantioseparation with cellulose-based chiral stationary phase was 51.9% and 15.4%, respectively. Using amylose-based chiral stationary phase we obtained 76.9% of baseline enantioseparations and 9.6% of partial enantioseparations of the tested compounds. The best results on cellulose-based chiral stationary phase were achieved particularly with propane-2-ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier and additive to CO2, respectively. Methanol and basic additive isopropylamine were preferred on amylose-based chiral stationary phase. The complementary enantioselectivity of the cellulose- and amylose-based chiral stationary phases allows separation of the majority of the tested structurally different compounds. Separation systems were found to be directly applicable for analyses of biologically active compounds of interest.

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.

OXPRENOLOL COMPOSITIONS FOR TREATING CANCER

The present invention relates to compositions of S-enantiomer enriched oxprenolol and their use in treating cancer and treating or preventing, in cancer patients, cachexia, body weight loss, lean body mass loss and adipose tissue loss, and improving quality of life and prolonging survival of cancer patients.

S-ENANTIOMERICALLY ENRICHED COMPOSITIONS OF BETA BLOCKERS FOR TREATING AMYOTROPHIC LATERAL SCLEROSIS

The present invention relates to S-enantiomerically enriched compositions of beta blockers and uses thereof, including uses of the beta blocker compositions for treating amyotrophic lateral sclerosis. The beta blocker compositions can also be used for preventing loss of lean mass, preventing body weight loss in subjects, improving quality of life in subjects, and prolonging survival in amyotrophic lateral sclerosis patients. The beta blocker can be oxprenolol or a pharmaceutically acceptable salt thereof.

Chiral separation of basic compounds on sulfated β-cyclodextrin-coated zirconia monolith by capillary electrochromatography

Sulfated β-cyclodextrin (SCD)-coated zirconia monolith was used as the chiral stationary phase in capillary electrochromatography for enantiomeric separation of basic chiral compounds. SCD adsorbed on the zirconia surface provided a stable chiral stationary phase in reversed-phase eluents. Retention, chiral selectivity and resolution of a set of six basic chiral compounds were measured in eluents of varying pH, composition of methanol and buffer. Optimum mobile phase condition for the separation of the compounds was found to be methanol content of 30%, buffer concentration of 30 mM and pH of 4.0.

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.

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.

FLUORESCENCE BASED DETECTION OF SUBSTANCES

A method for the fluorescent detection of a substance, the method comprising providing particles comprising a metal or a metal oxide core, wherein one or more optionally fluorescently tagged antibodies or human specific peptide nucleic acid (PNA) oligomers for binding to a substance is/are bound, directly or indirectly, to the surface of the metal or metal oxide; contacting a substrate, which may or may not have the substance on its surface, with the particles for a time sufficient to allow the antibody/PNA oligomer to bind with the substance; removing those particles which have not bound to the substrate; if the antibodies or PNA oligomers are not fluorescently tagged, contacting the substrate with one or more fluorophores that selectively bind with the antibody and/or substance, then optionally washing the substrate to remove unbound fluorophores; and illuminating the substrate with appropriate radiation to show the fluorophores on the substrate.

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.