EP0279844A1 - AFLÖSUNG VON DE dl-METHYL-3-4-(2-HYDROXY-3-ISOPROPYLAMINO)PROPOXY]PHENYLPROPIONAT (DL-ESMOLOL)] - Google Patents

AFLÖSUNG VON DE dl-METHYL-3-4-(2-HYDROXY-3-ISOPROPYLAMINO)PROPOXY]PHENYLPROPIONAT (DL-ESMOLOL)]

Info

Publication number
EP0279844A1
EP0279844A1 EP87905856A EP87905856A EP0279844A1 EP 0279844 A1 EP0279844 A1 EP 0279844A1 EP 87905856 A EP87905856 A EP 87905856A EP 87905856 A EP87905856 A EP 87905856A EP 0279844 A1 EP0279844 A1 EP 0279844A1
Authority
EP
European Patent Office
Prior art keywords
hydroxy
methyl
isopropylamino
esmolol
phenylpropionate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP87905856A
Other languages
German (de)
English (en)
Other versions
EP0279844A4 (fr
Inventor
Ghanshyam Patil
Khuong H. X. Mai
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bristol Myers Squibb Pharma Co
Original Assignee
EI Du Pont de Nemours and Co
DuPont Merck Pharmaceutical Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by EI Du Pont de Nemours and Co, DuPont Merck Pharmaceutical Co filed Critical EI Du Pont de Nemours and Co
Publication of EP0279844A1 publication Critical patent/EP0279844A1/fr
Publication of EP0279844A4 publication Critical patent/EP0279844A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids

Definitions

  • Isomeric compounds are generally obtained as racemates. Oftentimes, it is desirable to obtain one of the isomers, usually the l-isomer. Consequently, various methods have been devised for resolving racemic mixtures. Two methods are asymmetric synthesis or optical resolution. A representative process for optical resolution is described in U.S. Patent 3,649,691.
  • the above compound is an important beta-adrenergicblocking agent, its preparation and use is more fully described in the U. S. Patent Number 4,387,103.
  • dl-Esmolol as a free base, is treated with (-)-2,3:4,6-di- O-isopropylidene-2-keto-L-gulonic acid [(-)-(DAG)], employing aqueous acetone and water as a solvent, preferably in a ratio of 1:1 to 1:10 of acetone to water.
  • (-)-DAG-salt has the following optical rotations:
  • the free base is recovered by treating the above (+)-esmolol . (-)-DAG-salt with an inorganic base, e.g., sodium hydroxide, the (+)-esmolol . hydrochloride salt of this base has the following optical rotation in metnanol:
  • the free base is recovered by treating the above (-)-esmolol . (-)-DTT-(-) salt with an inorganic base, e.g., sodium hydroxide, the (-)esmolol-hydrochloride salt of this base has the following optical rotations:
  • the compounds of the invention may be converted into their pharmaceutically acceptable non-toxic acid addition salts by conventional procedures.
  • the acid addition salts may be prepared in the conventional manner by treating a solution or suspension of the free base in an organic solvent with the desired acid and then recovering the salts which form by crystallization techniques.
  • the desired non-toxic acids are the following: acetic, maleic, fumaric, succinic, tartaric, citric, malic, cinnamic, sulfonic, hydrochloric, hydrobr ⁇ mic, sulfuric, and phosphoric acid.
  • the compounds of the invention can be used in the treatment or prophylaxis of cardiac disorders.
  • M. Schwartz et al. report on Efficacy and Safety of Esmolol for Postoperative Atrial Fibrillation/Flutter.
  • esmolol racemic mixture
  • a therapeutic response was obtained in 9/15 patients, the median effective dose being 100 mcg/kg/ minute with a mean time to response of 22 minutes.
  • J. Askenazi et al. report on The Effect of Esmolol on Cardiac Hemodynamic Function.
  • the relative potency of l-esmolol and dl-esmolol was determined in the following manner. Mongrel dogs of either sex were anesthetized with a combination of nembutal and sodium barbital (15.0 and 300 mg/kg, respectively). A femoral artery and both femoral veins were cannulated for measurement of diastolic blood pressure and administration of drugs, respectively. Rectal temperature was monitored and maintained at 36-38°C. The vagus nerves were cut. Heart rate was measured from the arterial blood pressure signal with a Beckman cardiotachometer. Following surgical preparation, one hour was allowed for equilibration prior to initiating the experiment.
  • the relative potency of levo-esmolol and esmolol was determined utilizing ten-minute intravenous infusions of each compound at increasing doses. Each animal received both levo- esmolol and esmolol but the order of administration was randomized and a period of time for complete recovery from the effects of the first compound was allowed before initiating infusion of the other compound. Beta-blockade was assessed at the end of each ten-minute infusion period using bolus isoproterenol injections (0.5 ug/kg, i.v. bolus).
  • esmolol nor levo-esmolol modified baseline diastolic arterial blood pressure or diastolic arterial blood pressure responses to isoproterenol at any dose. 5 0

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Procédé de résolution de dl-méthyl 3-[4-(2-hydroxy-3-isopropylamino)propoxy]phénylpropionate [(dl-esmolol)] en un dextro (+) isomère et un lévo (-) isomère.
EP19870905856 1986-09-02 1987-08-25 AFLÖSUNG VON DE dl-METHYL-3-4-(2-HYDROXY-3-ISOPROPYLAMINO)PROPOXY]PHENYLPROPIONAT (DL-ESMOLOL)]. Withdrawn EP0279844A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US90280686A 1986-09-02 1986-09-02
US902806 1986-09-02

Publications (2)

Publication Number Publication Date
EP0279844A1 true EP0279844A1 (fr) 1988-08-31
EP0279844A4 EP0279844A4 (fr) 1990-06-05

Family

ID=25416420

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19870905856 Withdrawn EP0279844A4 (fr) 1986-09-02 1987-08-25 AFLÖSUNG VON DE dl-METHYL-3-4-(2-HYDROXY-3-ISOPROPYLAMINO)PROPOXY]PHENYLPROPIONAT (DL-ESMOLOL)].

Country Status (4)

Country Link
EP (1) EP0279844A4 (fr)
JP (1) JP2521317B2 (fr)
AU (1) AU607437B2 (fr)
WO (1) WO1988001614A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE8801518D0 (sv) * 1988-04-22 1988-04-22 Astra Pharma Prod A novel process
WO2009147430A1 (fr) 2008-06-02 2009-12-10 Generics [Uk] Limited Procédé pour la préparation d’amines énantiomériquement pures
BR112013018598A2 (pt) 2011-01-27 2016-10-18 Baxter Healthcare Sa composição farmacêutica, método para tratar uma doença cardíaca, uso de (s)-metil-3-[4-(2-hidroxi-3-[4-(2-hidroxi-3-isopropilamino) propoxi] fenilpropionato, e, método para controlar frequência cardíaca
CA2825311A1 (fr) * 2011-01-27 2012-08-02 Baxter International Inc. Methodes permettant de traiter la tachycardie et/ou de reguler la frequence cardiaque tout en minimisant et/ou regulant l'hypotension
CN113651706A (zh) * 2021-07-16 2021-11-16 湖州展望药业有限公司 一种高纯度盐酸艾司洛尔的制备工艺

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE8004087L (sv) * 1980-06-02 1981-12-03 Haessle Ab Nya parasubstituerade 3-fenoxi-1-alkylaminopropanol-2-er med betareceptorblockerande egenskaper, samt forfarande for deras framstellning, farmaceutiska beredningar innehallande desamma, och metod att behandla akut ...
US4593119A (en) * 1980-11-28 1986-06-03 American Hospital Supply Corporation Method for treatment or prophylaxis of cardiac disorders
US4387103A (en) * 1980-11-28 1983-06-07 American Hospital Supply Corporation Method for treatment or prophylaxis of cardiac disorders
EP0174956B1 (fr) * 1984-03-14 1990-08-16 BODOR, Nicholas S. AGENTS DE BLOCAGE $g(b)-ADRENERGIQUES DOUX

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
No relevant documents have been disclosed. *
See also references of WO8801614A1 *

Also Published As

Publication number Publication date
WO1988001614A1 (fr) 1988-03-10
JPH01500665A (ja) 1989-03-09
AU7911487A (en) 1988-03-24
EP0279844A4 (fr) 1990-06-05
AU607437B2 (en) 1991-03-07
JP2521317B2 (ja) 1996-08-07

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