54340-62-4

Usage

Originator

Bururalol hydrochloride,Onbio Inc.

Manufacturing Process

68.3 g (0.182 mol) of trimethyl-phenyl-ammonium perbromide were added in a single portion at 20°C to a stirred solution of 48.5 g (0.182 mol) of 5- bromo-2-acetyl-7-ethylbenzofuran in 400 ml of dry tetrahydro-furan. The resulting mixture was stirred at 20°C for 3 h, during which time trimethylphenyl- ammonium bromide precipitated out. The mixture was then poured into water and extracted 3 times with ether. The combined ether extracts were washed successively with water, saturated sodium bicarbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The solid residue was recrystallized from ethanol to yield 43.1 g of 5-bromo-2-bromoacetyl-7-ethylbenzofuran as yellow crystals, melting point 101-102°C. 1.35 g of sodium borohydride were added portion-wise at room temperature over a period of 20 min to a stirred solution of 17.3 g (0.05 mol) of 5-bromo- 2-bromoacetyl-7-ethylbenzofuran in 100 ml of dioxane and 25 ml of water. The mixture was stirred at room temperature for 3 h, then dioxane was removed by evaporation at 40°C under reduced pressure and the residue was diluted with water and extracted 3 times with ether. The combined ether extracts were worked up in the usual manner to yield 16.0 g of crude 5- bromo-2-(2-bromo-1-hydroxyethyl)-7-ethyl-benzofuran as a viscous oil. 16.0 g of crude 5-bromo-2-(2-bromo-1-hydroxyethyl)-7-ethylbenzofuran and 37.0 g of t-butylamine were heated at 100°C in a sealed autoclave for 24 h. After cooling, excess t-butylamine was evaporated off and the residue was taken up in dilute aqueous hydrochloric acid. The aqueous solution was washed twice with ether, basified with dilute aqueous sodium hydroxide solution and extracted twice with ether. The combined ether extracts were washed with water and with brine, dried over anhydrous sodium sulfate, filtered and evaporated. The solid residue was crystallized from petroleum ether (boiling point 60-80°C) to yield 4.7 g of 5-bromo-2-(2-t-butylamino-1- hydroxyethyl)-7-ethylbenzofuran as buff crystals, melting point 101-103°C. 4.8 g of 5-bromo-2-(2-t-butylamino-1-hydroxyethyl)-7-ethylbenzofuran in 50 ml of ethanol were hydrogenated at room temperature and atmospheric pressure in the presence of 0.3 g of 5% palladium-on-carbon catalyst. After the uptake of one equivalent of hydrogen, the hydrogenation was terminated, catalyst was filtered off and the filtrate was evaporated to dryness. The residue was basified and extracted twice with ether. The combined ether extracts were worked up in the usual manner to give 2-(2-t-butylamino-1- hydroxyethyl)-7-ethylbenzofuran in the form of an oil. In practice it is usually used as hydrochloride.

Therapeutic Function

Beta-adrenergic blocker

InChI:InChI=1/C16H23NO2/c1-5-11-7-6-8-12-9-14(19-15(11)12)13(18)10-17-16(2,3)4/h6-9,13,17-18H,5,10H2,1-4H3

Downstream Products

• 64100-62-5 (-)-Bufuralol 
• 64100-61-4 (+)-Bufuralol 
• 61470-08-4 4-Hydroxy-Bufuralol 

Relevant academic research and scientific papers

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.