6673-35-4

Usage

Uses

Used in Pharmaceutical Industry:
N-[4-[2-HYDROXY-3-[(1-METHYLETHYL)AMINO]PROPOXY]PHENYL]ACETAMIDE is used as a selective adrenergic β-receptor blocking drug for the treatment of hypertension. Its antihypertensive properties make it a valuable compound in managing high blood pressure and related cardiovascular conditions.
Used in Emergency Medicine:
N-[4-[2-HYDROXY-3-[(1-METHYLETHYL)AMINO]PROPOXY]PHENYL]ACETAMIDE is used as an emergency treatment for cardiac arrhythmias. Its selective β-receptor blocking action helps to regulate abnormal heart rhythms, providing a crucial intervention in life-threatening situations.

Originator

Eraldin, I.C.I. ,UK,1970

Manufacturing Process

The 1-(4-acetamidophenoxy)-2,3-epoxypropane used as starting material may be obtained as follows. To a solution of 4.5 parts of 4-acetamidophenol and 1.5 parts of sodium hydroxide in 50 parts of water at 15°C, there is added 3.5 parts of epichlorohydrin. The mixture is stirred for 16 hours at ambient temperature, filtered and the solid residue is washed with water. There is thus obtained 1-(4-acetamidophenoxy)-2,3-epoxypropane, MP 110°C.A mixture of 2 parts of 1-(4-acetamidophenoxy)-2,3-epoxypropane and 10 parts of isopropylamine is stirred at ambient temperature for 16 hours. The resulting solution is evaporated to dryness under reduced pressure and the residue is crystallized from butyl acetate. There is thus obtained 1-(4acetamidophenoxy)-3-isopropylamino-2-propanol, MP 134° to 136°C.

Therapeutic Function

Antiarrhythmic

World Health Organization (WHO)

Practolol, a beta-adrenoreceptor antagonist, was introduced in 1970 for the treatment of angina and cardiac dysrhythmias. By 1974 long-term use had been associated with serious delayed idiosyncratic reactions (oculomucocutaneous syndrome) and this led to the withdrawal of oral preparations by the major manufacturer on a worldwide basis. There is no evidence to suggest that other beta-adrenoreceptor antagonist are associated with this risk. Intravenous preparations of practolol remain available in many countries for the emergency treatment of selected cardiac dysrhythmias.

Biological Activity

Practolol is a potent and selective β1 adrenergic receptor antagonist. It can be used in the study of cardiac arrhythmias.

in vitro

Practolol (10 μM; 30 min) preferentially antagonizes the relaxant effects produced by R0363 in spontaneously contracted tracheal preparations from the guinea-pig.Practolol (10 nM-100 μM) blocks the progesterone production induced by (-)epinephrine in a dose-dependent manner in granulosa cells.

in vivo

Practolol (0.5 mg/kg; i.v.) decreases heart rate, left ventricular dP/dt max , myocardial blood flow and cardiac output in intact close-chest dogs.Practolol (0.5 mg/kg; i.v.) decreases normal myocardial blood flow but flow in the ischaemic area remains unchanged after coronary artery ligation.

InChI:InChI=1/C14H22N2O3/c1-10(2)15-8-13(18)9-19-14-6-4-12(5-7-14)16-11(3)17/h4-7,10,13,15,18H,8-9H2,1-3H3,(H,16,17)/p+1/t13-/m0/s1

Upstream product

• 98-95-3 nitrobenzene 
• 100-65-2 N-Phenylhydroxylamine 
• 1795-83-1 N-Phenylacetohydroxamic acid 
• 103-90-2 4-acetaminophenol 
• 6597-75-7 1-(4-acetamidophenoxy)-2,3-epoxypropane 
• 75-31-0 isopropylamine 

Downstream Products

• 57494-85-6 N-[4-(2-Hydroxy-3-isopropylamino-propoxy)-phenyl]-N-methyl-acetamide 
• 27684-79-3 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]benzenamine 
• 37936-66-6 (+)-Practolol 
• 37936-65-5 (-)-Practolol 
• 265669-12-3 3-[4-(3-iodoprop-2-enyloxycarbonylamino)phenoxy]-1-N-(tert-butoxycarbonyl)isopropylaminopropan-2-ol 
• 265669-10-1 3-[4-(prop-2-ynyloxycarbonylamino)phenoxy]-1-(N-tert-butoxycarbonyl)isopropylaminopropan-2-ol 
• 175532-42-0 3-[4-(amino)phenoxy]-11-N-(tertbutoxycarbonyl)isopropylaminopropan-2-ol 

Relevant academic research and scientific papers

Redox-Neutral Selenium-Catalysed Isomerisation of para-Hydroxamic Acids into para-Aminophenols

A selenium-catalysed para-hydroxylation of N-aryl-hydroxamic acids is reported. Mechanistically, the reaction comprises an N?O bond cleavage and consecutive selenium-induced [2,3]-rearrangement to deliver para-hydroxyaniline derivatives. The mechanism is studied through both 18O-crossover experiments as well as quantum chemical calculations. This redox-neutral transformation provides an unconventional synthetic approach to para-aminophenols.

The curved blade of the needle and needle cover for preventing mispuncture mispuncture prevention known airfoil with curved needle with a needle cover having a chemical injection device

PROBLEM TO BE SOLVED: To provide a needle cover for preventing erroneous needling for a winged curved needle, which dispenses with the remounting of the needle cover on the curved needle after use, reduces the possibility of erroneous needing to an operator, etc., and enhances safety for use. SOLUTION: The needle cover 1, 31 and 61 for the winged curved needle comprise approximately L-shaped housings 2, 32 and 62, which are formed integrally with a pair of first opposed side walls 3, 33 and 63 and a pair of second opposed side walls 4 and 34 in an approximate L-shape. First bottom walls 8 and 38 and 68 and second bottom walls 9, 39 and 39 are formed integrally in an approximately L-shape between the side walls 3, 33 and 63 and the side walls 4, 34 and 64. First openings 6, 36 and 66 and second openings 7, 37 and 67 communicating with one another are formed between the side walls 3, 33 and 63 and the side walls 4, 34 and 64, which face the bottom walls 8, 38 and 68 and the bottom walls 9, 39 and 69. Locking parts 5, 35 and 65 for the needle are formed in the interior wall surfaces of the side walls 3, 33 and 63, and openings 11, 41 and 71 are formed in the bottom walls 9, 39 and 69.

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.

Determination of the enantiomeric purity and the configuration of β- aminoalcohols using (R)-2-fluorophenylacetic acid (AFPA) and fluorine-19 NMR: Application to β-blockers

A method has been developed for determining the enantiomeric purity and the absolute configuration of β-aminoalcohols of type ArOCH2CH(OH)CH2NHR (R = iPr, tBu). To determine enantiomeric purity, the amine function was first protected by a benzyl group, then the compound formed was esterified using the acid chloride of (R)-2-fluorophenylacetic acid (AFPA). The 19F NMR analysis of the derivative obtained revealed the presence of two distinctly separate signals (~2.5 ppm), the one for the RS-SR pair being the most deshielded. The configuration was determined directly on the aminoalcohol by using the acid. In stoichiometric conditions, when R = iPr, the amide function was obtained very preponderantly. The 19F NMR spectrum of the amide presented four distinct signals when derivatization was carried out by means of a reaction between the (±)-β-aminoalcohol and the (R)-AFPA. The extreme signals, which were over 3.5 ppm apart, did not belong to the same diastereomer. With R = tBu essentially the ester function was obtained. The first studies revealed the presence of two signals, though not as clearly separated as in the previous cases. Each experiment was simple to perform, and purification was not necessary. Mosher's acid gave unsatisfactory results in each case. (C) 2000 Elsevier Science Ltd.

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.

Cardioselectivity as a function of molecular structure in β-adrenoceptor blocking agents of the 1-(para-substituted aryloxy)-3-(isopropylamino) propan-2-ol type

The relationship between molecular structure and cardioselectivity is described in the 1-(para-substituted aryloxy)-3-(isopropylamino)propan-2-ol type of β-adrenoceptor blocking agents. Cardioselectivity in the aforementioned series requires that the aromatic substitution in the position para to the amino alcohol side chain will have a minimal linear length of 5.0 A. Highest cardioselectivity is obtained when this para substituent is a rigid group coplanar with the aromatic ring. This may result from steric hindrance for binding at the β2-adrenoceptor subtype which does not occur in the β1 subtype. Evidence in favor of this suggestion was obtained by the finding that the trans isomer of 1-[4-(1-propenyl)-2-methoxyphenoxy]-3-(isopropylamino)propan-2-ol is cardioselective (β1/β2=25), whereas the cis isomer is β2 selective (β1/β2=0.1).