DE2839431A1 - Tranquilliser and hypertonic for heart and vascular disease treatment - contg. 1-(2-nitro-5-methylphenoxy)-3-tert.butyl-aminopropan-2-ol - Google Patents

Abstract

Pharmaceutical compsn. contains 1-(2-nitro-5-methyl-phenoxy)-3-tert. butyl-aminopropan-2-ol (I) or an acceptable acid addition salt, together with a suitable diluent or carrier. (I) can be used as a tranquilliser and antihypertonic in the treatment of various heart and vascular diseases. (I) produces an excellent blocking of the beta-receptors of the sympathicus. (I) has a better inhibitory effect against the increased contractions strength and beat frequency induced by isoprenalin in an isolated heart auricle than has Propranol. ED50 for (I) is 4.0 x 10-8 g./ml., cf. the ED50 for Propranol, which is 2.0 x 10-7 g./ml. The compsn. can be in the form of tablets, capsules, dragees, solns., suspensions or emulsions for oral use, injectable solns. or emulsions, dispersible powders or aerosol, adn can also contain >=1 other pharmaceutical, chosen from sedatives, antihydpertonics, diuretics, vasodilators, antiarrhythmics, agents for treatment of Parkinson's disease, cardiotonic agents, bronchodilators and sympathomimetic agents.

Description

drug

The invention relates to i- (2-methyl-5-nitro-phenoxy) -3-tert-butylamino-propan-2-ol, which creates an excellent blockade of the B receptors of the sympathetic nervous system.

In recent years, compounds have had blocking activity towards ß-adrenergic receptors increasingly gained in importance, among other things as drugs for various heart and vascular diseases such as cardiac arrhythmias and angina pectoris, as tranquilizers, as antihypertensive drugs.

Propranolol is known. Compared to this, the 1 - (2-methyl-5-nitro-phenoxy) -3-tert. -butylamino-propan-2-ol (A) has a far better inhibiting effect with regard to the increased contraction force and impact frequency of the isolated one due to isoprenaline Auricle.

A ED50 4.0 x 10-8 g / ml Propranol ED50 2.0 x 10- g / ml The invention Compound can therefore be used on its own, generally as a pharmaceutically acceptable one Acid addition salt, both inorganic and organic acids as acids are suitable, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfur, Nitric, phosphorus, vinegar, glucone, milk, Malon-g Malein, amber, fumar, Tartaric, lemon, benzoin, ß-oxynaphthol, embon, or theopwyllinessetic acid, or in mixtures with other pharmaceutically acceptable diluents or carriers in pharmaceutical preparations. The pharmaceutical Preparations can be in the form of e.g. tablets, capsules, coated tablets, orally administrable, aqueous or oily solutions or suspensions, emulsions, injectable aqueous or oily solutions or suspensions, dispersible powders or aerosol mixtures are present.

In addition to the compound according to the invention, one or several pharmaceutically active substances may be contained in the drug, such as Sedatives, e.g.

Phenobarbital, meprobamate, chlorpromazine or benzodiazepines, hypotensive Agents, e.g. Rauwolfia alkaloids, bethanidine or guanethidine, diuretics, e.g. chlorothiazide, Vasodilators, e.g. glycerol trinitrate, erythritol tetranitrate or isosorbide dinitrate, Antiarrhythmics, e.g., quinine, agents used to treat Parkinson's disease serve e.g. trihexyphenidyl, cardiotonic agents e.g.

Digitalis preparations, bronchodilators and sympathomimetic agents, e.g. adrenaline, isoprenaline, orciprenaline or ephedrine.

Suitable pharmacologically inert excipients are e.g.

for tablets and coated tablets: lactose, starch, talc, stearic acid for injection solutions: water, alcohol, glycerine, vegetable oils.

Furthermore, the preparations can also contain preservative, stabilizing or wetting agents, solubilizers, sweeteners or coloring agents, flavorings, etc. contain.

Example 1: 10.5 g of 1- (2-nitro-5-methyl-phenoxy) -2. 3-epoxy propane are with abs in 100 ml. Ethanol heated under reflux for about 8 hours. After distilling off of the alcohol in vacuo, the residue is dissolved in benzene. In this benzene solution hydrogen chloride is passed in with ice-cooling until saturation is reached. The unusual one Precipitate is filtered off with suction, washed with acetone and recrystallized from ethanol.

FP.

Analysis: C14H22N2 ° 4 x HCl mol. Wt. 318,807 calc.

C 52.74% 52.80% H 7.27% 7.36% N 8.79% 8.71% example 2: 1- (2-Nitro-5-methyl-phenoxy) -3-tert-butyl-aminopropan-2-ol hydrochloride 25 mg Magnesium stearate 1 mg polyvinylpyrrolidone 5 mg talc 10 mg corn starch 15 mg lactose 92 mg Polyethylene glycol 6000 2 mg For a tablet of 150 mg The active ingredient is mixed with polyvinylpyrrolidone, corn starch, lactose and polyethylene glycol 6000. The mass is moistened with water, kneaded until it can be granulated and dried. After drying, the granules are passed through a sieve with a mesh size of 1.0 mm and mixed in a suitable mixer with talc and magnesium stearate and used for Compressed tablet.

Claims (4)

P a t e n t a n s p r ü c h e: 1. Pharmaceutical compositions, characterized in that it is 1- (2-nitro-5-methyl-phenoxy) -3-tert-butylamino-propan-2-ol or a pharmaceutically acceptable acid addition salt thereof together with a pharmaceutically acceptable diluent or carrier. 2. Pharmaceutical compositions according to claim 1, characterized in that that they are in the form of tablets, capsules, coated tablets, orally administrable solutions, Suspensions or emulsions, injectable solutions or emulsions, dispersible Powders or aerosols are present. 3. Pharmaceutical compositions according to claim 1 or 2, characterized characterized in that they additionally contain one or more pharmaceutical substances, those consisting of sedatives, antihypertensive drugs, diuretics, vasodilators, antiarrhythmics, Agents used to treat Parkinson's disease are cardiotonic Agents, bronchodilators and sympathomimetic agents are selected. 4. Pharmaceutical compositions according to claim 1, 2 and 3, characterized characterized in that the pharmaceutical preparations as a drug against various Cardiovascular disease can be used as a tranquilizer and antihypertensive agent can.