37517-30-9

Basic information

• Product Name: Acebutolol
• Synonyms: (.+/-.)-3'-Acetyl-4'-[2-hydroxy-3-(1-methylethylamino)propoxy]butyranilide;(.+/-.)-3'-Acetyl-4'-[2-hydroxy-3-(isopropylamino)propoxy]butyranilide;(.+/-.)-N-(3-Acetyl-4-(2-hydroxy-3-((1-methylethyl)amino)propoxy)phenyl)butanamide;1-(2-Acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane;3'-Acetyl-4'-(2-hydroxy-3-(isopropylamino)propoxy)butyranilide;5'-Butyramido-2'-(2-hydroxy-3-isopropylaminopropoxy)acetophenone;Butanamide, N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]-, (.+/-.)-;dl-Acebutolol
• CAS NO: 37517-30-9
• Molecular Formula: C₁₈H₂₈N₂O₄
• Molecular Weight: 336.43
• EINECS: 253-539-0
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Adrenoceptor
• Mol File: 37517-30-9.mol
• Article Data: 7

Chemical Properties

• Melting Point: 119-123°C
• Boiling Point: 472.9°C (rough estimate)
• Flash Point: 295 °C
• Appearance: Crystalline solid
• Density: 1.1748 (rough estimate)
• Vapor Pressure: 1.45E-13mmHg at 25°C
• Refractive Index: 1.5700 (estimate)
• Storage Temp.: -20°C Freezer
• PKA: pKa 9.40 (Uncertain)
• Water Solubility: 259 mg/L
• CAS DataBase Reference: Acebutolol(CAS DataBase Reference)
• NIST Chemistry Reference: Acebutolol(37517-30-9)
• EPA Substance Registry System: Acebutolol(37517-30-9)

Safety Data

• Hazardous Substances Data: 37517-30-9(Hazardous Substances Data)

Usage

Chemical Properties

Crystalline Solid

Uses

Acebutol is 3′-acetyl-4′-[2-hydroxy-3-(iso-propylamino)propoxy] butyranilide (12.1.6) [9,10].Acebutol is a selective β1-adrenoblocker. It possesses antianginal, antihypotensive, and antiarrhythmic action. It is used for arterial hypertension, preventing attacks of angina, and cardiac rhythm disturbances.

Definition

ChEBI: An ether that is the 2-acetyl-4-(butanoylamino)phenyl ether of the primary hydroxy group of 3-(propan-2-ylamino)propane-1,2-diol.

Therapeutic Function

beta-Adrenergic blocker

General Description

Acebutolol is one of the very few β-blockers whosemetabolite plays a significant role in its pharmacological actions.This drug is absorbed well from the gastrointestinaltract, but it undergoes extensive first-pass metabolic conversionto diacetolol by hydrolytic conversion of the amidegroup to the amine, followed by acetylation of the amine. After oral administration, plasma levels of diacetololare higher than those of acebutolol. Diacetolol is also aselective β1-blocker with partial agonistic activity; it has littlemembrane-stabilizing activity. It has a longer half-life (8–12hours) than the parent drug and is excreted by the kidneys.

Clinical Use

Acebutolol (Sectral) is a cardioselective 1-adrenoceptor blocking agent that also has some minor membrane stabilizing effects on the action potential. Acebutolol is effective in the management of the patient with essential hypertension, angina pectoris, and ventricular arrhythmias. Antiarrhythmic effects are observed with the patient both at rest and taking exercise.

Side effects

Adverse effects include bradycardia, gastrointestinal upset, dizziness, and headache.

Safety Profile

Moderately toxic by intravenousroute. Human systemic effects by ingestion: developmentalabnormalities of the cardiovascular and respiratory systems;effects on newborn in biochemical and metabolicabnormalities and reduced growth statistics. A humanter

Drug interactions

Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Analgesics: NSAIDs antagonise hypotensive effect. Anti-arrhythmics: increased risk of myocardial depression and bradycardia; increased risk of bradycardia, myocardial depression and AV block with amiodarone; increased risk of myocardial depression and bradycardia with flecainide. Antidepressants: enhanced hypotensive effect with MAOIs. Antihypertensives: enhanced hypotensive effect; increased risk of withdrawal hypertension with clonidine; increased risk of first dose hypotensive effect with post-synaptic alpha-blockers such as prazosin. Antimalarials: increased risk of bradycardia with mefloquine. Antipsychotics enhanced hypotensive effect with phenothiazines. Calcium-channel blockers: increased risk of bradycardia and AV block with diltiazem; hypotension and heart failure possible with nifedipine and nisoldipine; asystole, severe hypotension and heart failure with verapamil. Cytotoxics: possible increased risk of bradycardia with crizotinib. Diuretics: enhanced hypotensive effect. Fingolimod: possibly increased risk of bradycardia. Moxisylyte: possible severe postural hypotension. Sympathomimetics: severe hypertension with adrenaline and noradrenaline and possibly with dobutamine.

Metabolism

About half of an orally administered dose of acebutolol (Sectral) is absorbed. Approximately 25% of the drug is bound to plasma proteins, and its plasma halflife is about 4 hours.Metabolism of acebutolol produces a metabolite with -blocking activity whose half-life is 10 hours.

Precautions

Acebutolol should not be administered in cardiogenic shock, uncontrolled heart failure, or severe bradycardia or to patients with known hypersensitivity to the drug.

InChI:InChI=1/C18H28N2O4/c1-5-6-18(23)20-14-7-8-17(16(9-14)13(4)21)24-11-15(22)10-19-12(2)3/h7-9,12,15,19,22H,5-6,10-11H2,1-4H3,(H,20,23)

Synthetic route

cyclopropanecarboxylic acid 2-(2-acetyl-4-butyrylamino-phenoxy)-1-(isopropylamino-methyl)-ethyl ester → Acebutolol (37517-30-9) + cyclopropanecarboxylic acid (1759-53-1)

Conditions	Yield
With water at 37℃; pH=1 - 12; Kinetics; Further Variations:; Reagents; Hydrolysis;

3-iodobenzoyl chloride (1711-10-0) + Acebutolol (37517-30-9) → N-[3-Acetyl-4-(2-hydroxy-3-isopropylamino-propoxy)-phenyl]-3-iodo-benzamide (67014-20-4)

Conditions	Yield
(i) aq. HCl, (ii) /BRN= 1860418/; Multistep reaction;

Acebutolol (37517-30-9) + cyclopropanecarboxylic acid chloride (4023-34-1) → cyclopropanecarboxylic acid 2-(2-acetyl-4-butyrylamino-phenoxy)-1-(isopropylamino-methyl)-ethyl ester

Conditions	Yield
Acylation;

Acebutolol (37517-30-9) → (R)-acebutolol + (S)-acebutolol

Conditions	Yield
With AmyCoat (150x46 mm, 3 μm size silica particle) In ethanol; n-heptane; diethylamine at 27℃; Resolution of racemate;
With diethylamine In acetonitrile Reagent/catalyst; Resolution of racemate;
With isopropylamine; trifluoroacetic acid In methanol at 35℃; under 103432 Torr; Reagent/catalyst; Solvent; Resolution of racemate; Supercritical conditions;
With triethylamine In methanol; water at 20℃; Resolution of racemate; Green chemistry; enantioselective reaction;

Acebutolol (37517-30-9) + 2,3,4-tri-O-acetyl-α-D-arabinopyranosyl isotyhiocyanate (62414-75-9) → C30H43N3O11S

Conditions	Yield
at 55℃; for 1h;

Acebutolol (37517-30-9) → C18H27(125)IN2O4

Conditions	Yield
With sodium (¹²⁵I)iodide; chloroamine-T; sodium hydroxide In water at 20℃; pH=4; Concentration; pH-value; Temperature; Time;

Acebutolol (37517-30-9) → acetolol (57898-80-3)

Conditions	Yield
With hydrogenchloride In water at 100℃; for 5h;

Downstream Products

• 57898-80-3 acetolol 
• 68107-82-4 (R)-acebutolol 
• 68107-82-4 (S)-acebutolol 
• 67014-20-4 N-[3-Acetyl-4-(2-hydroxy-3-isopropylamino-propoxy)-phenyl]-3-iodo-benzamide 

Relevant articles and documents

A new cardioselective -adrenoceptor blocking agent.

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FLUORESCENCE BASED DETECTION OF SUBSTANCES

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