DE2034277A1 - 1-(3-hydroxyphenyl)-2-(1-(4-(2-hydroxy or ethoxy)-phenyl) - propyl-2-amino)-ethanol-(1)-with bronchodilatory action - Google Patents

Abstract

Aminoalcohols of general formula (I): (where R = 1-3C alkylene and A = H or lower alkyl), exhibit strong bronchodilatatory action and are used in the treatment of asthma in man. Specif., R = H or Et and A = (CH2)2. Prepn. is by reducting condensation of 1-(3-HO-phenyl)-2-aminoethanol with a ketone of general formula (II) in the presence of a hydrogenating catalyst then converting the product as required into a salt with an acid. Suitable catalysts are Pd, Pt, PtO2 and NaBH4.

Description

Pharmacologically active amino alcohols and their preparation The invention relates to pharmacologically active amino alcohols of the general formula in which A is a lower alkylene group of 1 to 3 carbon atoms and R is a hydrogen atom or a lower alkyl group, as well as their salts formed with physiologically acceptable traces. The invention also relates to the two compounds 1- (3-hydroxyphenyl) -2- 74- (2-hydroxyethoxy) -phenyl / -propyl- (2) -amino # -ethanol- (1) and 1- (3-hydroxyphenyl) ) -2- # 1- [4- (2-ethoxyethoxy) -phenyl] propyl- (2) -amino # -ethanol- (1) and their physiologically acceptable salts.

The compounds of general formula I have the most experimental Guinea pig histamine asthma has strong bronchodilator properties and are characterized in particular by their good resorbability from the gastrointestinal tract the end. In the case of oral administration, the animals are protected from being caused by histamine Asthma attack 20 mg / kg body weight of the compounds according to the invention required, with parenteral administration about 12 to 14 mg / kg body weight; from these alone The good absorption from the gastrointestinal tract can be clearly seen in the ratio values.

In contrast, those used for the treatment of asthma are used in human medicine most commonly used compounds, 1- (3,5-dihydroxyphenyl) -2-isopropylaminoethanol and 1- (3,4-Dihydroxyphenyl) -2-isopropylaminoShanol, not or only very weakly orally effective. It was unsuccessful by oral application of either of the two compounds Protect guinea pigs from an H-istamine-induced athma attack. Apparently these compounds are only insufficiently absorbed from the gastrointestinal tract. There the cardiovascular activity of the compounds according to the invention is relatively low is, they should be used in therapy as anti-asthmatics.

The invention also relates to a process for the preparation of compounds of the general formula I in which A and R have the meaning given above, which is characterized9 that 1- (3-hydroxyphenyl) -2-aminoethanol- (1) with a ketone of general formula in which A and R have the meaning given above, are condensed reducing in the presence of a hydrogenation catalyst and then optionally converted into their salts with physiologically acceptable acids. The starting compounds are known from the literature; as far as the starting ketone was not known, it was prepared from 4-acetonylphenol by the usual etherification.

Noble metals or their oils, but can be used as hydrogenation catalysts the mixed hydrides such as sodium borohydride can also be used.

Example 1 1- (3-Hydroxyphenyl) -2- # 1- [4- (2-ethoxyethoxy) phenyl] propyl (2) amino # ethanol (1) p-aminobenzoate 10 g of 1- (3-hydroxyphenyl) -2-aminoethanol- (1) monohydrate and 13.8 g of 1- [4- (2-ethoxyethoxy) phenyl] propan-2-one are dissolved in 150 ml of methanol and shaken at 230 ° C. and slightly overpressure hydrogenated over 0.5 g of platinum oxide until the theoretical amount of hydrogen has been absorbed.

After filtering off the catalyst, the solvent is used in a rotary evaporator removed, the syrupy residue obtained was dissolved in ether and extracted with water. The ether phase is dried over sodium sulfate and added to the calculated amount p-Aminobenzoic acid, dissolved in methanol, added. The solvents are in a rotary evaporator evaporated and the crystalline residue obtained washed with ether. It will 18.5 g of 1- (3-hydroxyphenyl) -2- # 1- [4- (2-ethoxyethoxy) phenyl] propyl (2) amino # ethanol (3) p-aminobenzoate with a melting point of 70-75 ° C obtained for r c2rH29N04 * .C7H7N02 calculated: C 67.10%; H 7,) 5%; N 5.59%; found: C, 67.10%; H 7.28 "; N 5.48%.

Example 2 1- (3-Hydroxyphenyl) -2- # 1- [4- (2-hydroxyethoxy) phenyl] propyl - (2) -aminoi-ethanol- (l) -p-aminobenzoate This compound was made analogously to the example 1 from 8.5 g of 1- (3-hydroxyphenyl) -2-aminoethanol- (1) monohydrate and 11.5 g 1- [4- (2-Hydroxyethoxy) phenyl] propan-2-one manufactured.

The yield is 10 g of 1- (3-hydroxyphenyl) -2- # 1- [4- (2-hydroxyethoxy) phenyl] propyl (2) amino # ethanol (1) p-aminobenzoate with a melting point of 800 C.

Calculated for C19H25NO4 # C7H7NO2: C 65.40%; H 6.98%; N 5.68%; found: C 65.55%; H 6.86%; N 5.65%.

Claims (4)

P a t e n t a n s p r ü c h e 1) Compounds of the general formula in which A is a lower alkylene group with 1 to 3 carbon atoms and R is a hydrogen atom or a lower alkyl group with 1 to 3 carbon atoms, as well as their salts formed with physiologically acceptable acids. 2) The compound 1- (3-hydroxyphenyl) -2- 1 / 4- (2-hydroxy = ethoxy) -phenyl] -propyl- (2) -amino # -ethanol- (1). 3) The compound 1- (3-hydroxyphenyl) -2- # 1- [4- (2-ethoxyethoxy) -phenyl] -propyl- (2) -amino # -ethanol- (1). 4) Process for the preparation of compounds of the general formula I in which A and R have the meanings given above, characterized in that 1- (3-hydroxyphenyl) 2-aminoethanol- (1) with a ketone of the general formula in which A and R have the meaning given above, are condensed in a reducing manner in the presence of a hydrogenation catalyst and then optionally converted into their salts with physiologically acceptable acids.