42864-78-8 Usage
Uses
Used in Pharmaceutical Industry:
Bevantolol hydrochloride is used as an antianginal agent for the treatment of angina pectoris, a condition characterized by chest pain due to insufficient blood supply to the heart muscle. It helps to reduce the workload on the heart and alleviate the symptoms of angina.
Bevantolol hydrochloride is used as an antihypertensive agent for the management of hypertension (high blood pressure). It helps to lower blood pressure by blocking the β1-adrenergic receptors, which in turn reduces heart rate and the force of heart contractions.
Bevantolol hydrochloride is used as an antiarrhythmic agent for the treatment of abnormal heart rhythms (arrhythmias). It helps to stabilize the heart's electrical activity by blocking the β1-adrenergic receptors, which can contribute to the development of arrhythmias.
Additionally, Bevantolol hydrochloride has been shown to prevent immobilization stress-induced increases in systolic blood pressure in a rat model of stress-induced hypertension, indicating its potential use in managing stress-related cardiovascular issues.
Brand names for Bevantolol hydrochloride include Vantol (Parke-Davis) and Ranestol.
Originator
Warner-Lambert (USA)
Manufacturing Process
To a solution of 50 g (1.25 mol) of NaOH in 1200 ml H2O was added 108 g (1
mol) of m-cresol freshly distilled and at 15°C in one lot 117ml (1.5 mol) of
epichlorohydrin. The emulsion was stirred at room temperature for 16 hours in
a creased flask. The product was taken up in 1000 ml of toluene and washed
with 500 ml water. Distillation yielded 135.7 g=82% of 3-(m-tolyloxy)-1,2-
epoxypropane, b.p. 61°C at 0.05 mm.
Preparation of bevantolol hydrochloride:
To a suitable reactor under a nitrogen blanket is added 13.7 kg of β-(3,4-
dimethoxyphenyl)ethylamine. The amine is cooled to 5°C and 12.5 kg of 3-
(m-tolyloxy)-1,2-epoxypropane is added maintaining the temperature between
5-10°C. After 10 hours, the mixture is seeded with bevantolol free base;
seeding is repeated approximately every 2 hours until it is evident that
crystallization has started. After stirring for 48 hours at 10°C, 26 L of hexane
is added. The temperature is raised to 25°C and stirring is continued for 48
hours. The slurry is filtered and the collected solid is dried under vacuum. The
product is dissolved in 60 L of isopropyl alcohol and the solution is filtered.
The reactor and filter are rinsed with 186 L of isopropyl alcohol and 2.7 kg of
anhydrous hydrogen chloride is added to the combined filtrate. The batch is
heated to reflux for 2 hours. The temperature is adjusted to 65°C and the
solution is seeded with bevantolol hydrochloride crystals. The mixture is held
at this temperature with stirring until a heavy sand-like slurry is present. The
mixture is allowed to cool to ambient temperature without stirring or artificial
cooling. It is then cooled to 20°C. The slurry is centrifuged and the product
rinsed with isopropyl alcohol until the filtrate is colorless. After being vacuum
dried at 50-55°C the product is milled if necessary; yield of bevantolol
hydrochloride 22.7 kg (78.6%); melting point 137-138°C.
Hazard
Moderately toxic by ingestion.
Safety Profile
A poison by intraperitoneal andintravenous route. Moderately toxic by ingestion. Whenheated to decomposition it emits toxic vapors of NOx,HCl, and Cl-.
Check Digit Verification of cas no
The CAS Registry Mumber 42864-78-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 4,2,8,6 and 4 respectively; the second part has 2 digits, 7 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 42864-78:
(7*4)+(6*2)+(5*8)+(4*6)+(3*4)+(2*7)+(1*8)=138
138 % 10 = 8
So 42864-78-8 is a valid CAS Registry Number.
InChI:InChI=1/C20H27NO4.ClH/c1-15-5-4-6-18(11-15)25-14-17(22)13-21-10-9-16-7-8-19(23-2)20(12-16)24-3;/h4-8,11-12,17,21-22H,9-10,13-14H2,1-3H3;1H
42864-78-8Relevant articles and documents
The effective direct resolution procedure for the chiral drug bevantolol hydrochloride
Bredikhina, Zemfira A.,Antonovich, Olga A.,Zakharychev, Dmitry V.,Bredikhin, Alexander A.
, p. 397 - 403 (2016/05/19)
The solubility of the chiral drug bevantolol hydrochloride 1 in water and the azeotropic mixture ethanol-water has been investigated. It was found that rac-1 meets the requirements of Meyerhoffer's rule, so it was possible to reduce the ternary diagram, describing the solubility of 1, to a pseudo binary form, which facilitates the analysis of crystallization processes caused by temperature changes. On this basis, the effective and robust resolution procedure of racemic bevantolol hydrochloride by a preferential crystallization approach has been realized successfully.
One more chiral drug prone to spontaneous resolution: Binary phase diagram, absolute configuration, and crystal packing of bevantolol hydrochloride
Bredikhina, Zemfira A.,Zakharychev, Dmitry V.,Gubaidullin, Aidar T.,Bredikhin, Alexander A.
experimental part, p. 171 - 176 (2010/03/26)
Spontaneous resolution of cardioselective β1-adrenergic blocker bevantolol hydrochloride 1·HCl was established by IR spectroscopy, differential scanning calorimetry, and by single crystal X-ray analysis both for enantiopure and racemic samples.
Process for preparation of bevantolol hydrochloride
-
, (2008/06/13)
Disclosed is a new process for preparing bevantolol hydrochloride suitable for industrial production in which bevantolol hydrochloride can be obtained in a high yield and HVA of an expensive material can be recovered. The process for the preparation of bevantolol hydrochloride comprises the steps of: causing 3-(m-tolyloxy)-1,2-epoxypropane (TOEP) to react with β-(3,4-dimethoxyphenyl)ethylamine (HVA) of excess mole per mole of said TOEP; dissolving the reaction mixture in a halogenated hydrocarbon to give a solution; mixing the solution with hydrochloric acid; separating an organic layer from the resulting mixture; and obtaining 1-[(3,4-dimethoxyphenethyl)amino]-3-(m-tolyloxy)-2-propanol hydrochloride from the organic layer.
