DE1643459C3 - 1 - (2-Methoxyphenoxy) -3-tert-butylamino-2-propanol and its salts, processes for their preparation and pharmaceuticals - Google Patents

Description

IS

OCH ₃

OCH ₂ -CH-CH ₂ -NH-NC ₄ H ₉

OH

The invention relates to the subject matter defined in the claims.

Recently, the focus has been on the manufacture of pharmacologically active compounds concentrated, which have a / f-adrenergic inhibiting or blocking effect. This effect is generally of great value in the treatment and management of angina Cardiac arrhythmia and to reduce certain types of obstruction of those away from the heart Arteries in congenital and acquired heart damage.

Albeit extensive research aimed at discovering a useful one / i-adrenergic inhibitor, the remedies so far manufactured are either a high degree of effectiveness in suppressing the acceleration of the pulse caused by isoproterenol is brought about, owns. Furthermore, it shows no noticeable effect on the normal mean Blood pressure, however, exhibits dose-related inhibition of antihypertensive drugs Response to isoproterenol. They also have a low toxicity.

The superiority comes from the following test report emerged:

Anesthetized dogs were used as test animals for the experiments. These were stimulated with isoproterenol. Then you gave the / i-blocker to be tested intravenous. The table shows the amount of active ingredient necessary to increase the Blocking the heartbeat and blood pressure caused by isoproterenol.

Tested connection

/ (- blocker effect
ED ₅₀ (mg / kg)

Toxicity
LD ₅₀ (mg / kg)

Heartbeat blood pressure oral

intraperitoneally

- O - CH ₂ - CH -CH ₂ - NHCH (CH ₃ ) ₂ CO OH ■ HCl (Propranolol) OCH ₃
C /, • HCl O - CH ₂ - CH - CH ₂ - NHC (CH ₃ I ₃

0.028 *) 0.041

368

114

0.012 *) 0.039 420

168

OH

(compound according to the invention)

*) Average of 2 attempts.

The compound of the invention can be conveniently prepared by treating 1- (2-methoxyphenxy) -3-halo-2-propanol with tertiary butylamine. The time taken to carry out the reaction, as indicated in the examples, is not binding as longer periods of time can be used provided that this does not result in excessive decomposition of the starting materials or the product. However, a satisfactory shorter period of time can also be determined by periodic analysis for ionically bound chlorine in the reaction mixture. The reaction can be carried out at temperatures from about room temperature to about 150 ° C, although the preferred reaction temperature is about 100 ⁰ C. Even if the example uses a large excess of tert-butylamine without a solvent, a smaller amount of amine can advantageously be used in the presence of an inert solvent, e.g. By employing one equivalent of the amine in an alkanol such as ethanol, thus enabling the immediate isolation of the hydrohalide of the product by diluting the reaction mixture with ether.

The amine formed can be isolated by known methods; such a procedure is described in the example. However, it is preferred to use the amine as the pharmaceutically acceptable acid addition salt to isolate. Albeit the preferred method of making the acid addition salts with If aqueous acid takes place, they can just as well, for example, with alcoholic acid or by treatment a solution of the free base in an inert solvent such as ether with an anhydrous acid, e.g. B. Hydrogen chloride.

The following example explains the invention.

example

1- (2-Methoxyphenor.y) -3-teri.-butylamino-2-propanol hydrochloride

A. l- (2-Methoxyphenoxy) -3-tert-butylamino-

2-propanol

A mixture of 52.4 g of 1- (2-methoxyphenoxy) -3-chloro-2-propanol is kept and 65 g of tert-butylamine

ίο on a steam bath refluxing for 116 hours, during which time the mixture turns yellow with the formation of solids. You acidify with 250 ml of 6N hydrochloric acid, extracted several times with diethyl ether, the ether extracts washed several times with water, makes the combined aqueous extracts basic with dilute sodium hydroxide solution and extracted them four times with diethyl ether, then washed the combined ether extracts several times with water and evaporates to dryness. 52.6 g of l- (o-methoxyphenoxy) - 3 - tert are obtained. - butyJamino - 2 - propanol as Solid.

B. l- (2-methoxyphenoxy) -3-tert-butylamino-

2-propanol hydrochloride

The solid product obtained according to A is dissolved in 60 ml of 4N hydrochloric acid, evaporated to dryness and the dried solid is recrystallized from ethanol-diethyl ether. 48.1 g of 1- (2-methoxyphenoxy) - 3 - tert are obtained. - butylamino - 2 - propanol -. Hydrochloride, mp 140-142 ⁰ C. Further recrystallization from ethanol-diethyl ether gives an analytical sample, melting at 142-143 ° C.

Analysis for C ₁₄ H ₂₄ ClNO ₃ :

Calculated ... C 58.02, H 8.35, N 4.83%;
found .... C 57.78, H 8.19, N 4.85%.

Claims (3)

Patent claims: 1. 1- (2-Methoxyphenoxy) -3-tert-butylamino-2-propanol and its pharmaceutically acceptable acid addition salts. 2. Process for the preparation of the compound according to claim 1, characterized in that l- (2-methoxyphenoxy) -Vhalogen-2-propanol with tert-butylamine is used in a manner known per se reacted and optionally treated the base formed with an appropriate acid. 3. Medicament containing a compound according to claim 1 as an active ingredient. inadequate in terms of their pharmacological activity, or because they are toxic or otherwise undesirable Have side effects and thus their pharmaceutical dosage and general applicability is restricted. There is therefore a continuing need for effective / i-receptor blockers. It has now been found that the 1 - (2 - methoxyphenoxy) - 3 - tert according to the invention. - butylamino - 2 - propanol of formula I.