IL35378A - Derivatives of 1-amino-3-phenoxy-2-propanol and process of preparation - Google Patents

Description

of and Process of Preparation New derivatives of and process of preparation named The present invention has as object new derivatives of as well as a process for preparing these The invention has more particularly as object derivatives of of general formula I in which Ar represents an or cyclopropylp enyl and and represent a hydrogen a chain or branched alkyl radical containing carbon atoms or a cycloalkyl radical containing from to 7 carbon at least one of the radicals or not being as well as their therapeutically compatible mineral or organic acid or quaternary ammonium Among the mineral or organic acid salts of the compounds of formula one chooses preferably those obtained with of formula one chooses preferably those obtained with alkyl halides such for methyl or halides such for hydrox ethyl bromide or alkyl sulphates such for dimethyl alkyl alkylsulphonates or alkyl such as methyl methane or toluene The new which are the object of the are endowed with very interesting pharmacological they exercise specifically a remarkable inhibiting activity on the receptors of the organism and possess in addition a low Among these compounds one can mention hydrochloride hydrochloride cyclohexylsulphamate diethyl methyl ammonium hydrochloride The process for preparing the compounds of formula I and their which is likewise ob ect of the is characteri ed in that an amino of formula in which and have the already indicated is to react with epoxide of in which Ar has the already if the compound of formula I thus obtained is to react with a therapeutically compatible mineral or organic acid or a quaternizing agent to the desired In the operation of the process of preparation according to the preferably one operates at present as A of epoxide of formula with an excess of amine of formula is brought to a temperature between and operating in solvent inert with respect to the products undergoing such a solvent can for example be an aliphatic alcohol a low molecular The medium is kept under agitation for 1 to 10 hours when the reaction has the solvent and the excess amine of formula is eliminated by concentration and the desired product is for example by The addition salts the acids of the derivatives of formula are advantageously prepared by operating in a solvent or a mixture of preferably such as ethyl ethanol or The quaternary ammonium salts of the derivatives of are methanol ethanol new which are the object of the because of their very in properties and specifically their inhibiting properties on the are used in in the treatment of angina pectories and disorders of cardiac chiefly of auricular fibrilla The usual dose varies to the produc the subject the complaint in question and the route of It can for example be y oral route in the The which are the object of the can in the form of pharmaceutical These compositions are produced in such a way as to be administered by digestive or parenteral They can be solid or liquid and can be in the form of plain or injectable they are prepared the usual The active principle or principles can be incorporated therein with excipients usually in these pharmaceutical compositions such as gum magnesium aqueous or various dispersing or emulsifying The compounds of formula used as starting materials for carrying out the invention can be obtained by causing a substituted phenol of formula alkaline operates preferably by adding propane to the solution of phenol in an aqueous solution of After reaction at the desired compound of is separated by the usual methods such as extraction with ether followed by concentration and The following examples illustrate the invention without however limiting it 1 1 One heats in an autoclave at for 4 hours a mixture of 11 of of isopropylamine and of One eliminates the excess isopropanol and by concentration under reduced one distills the residue and obtains a product whic crystallizes on Boiling point under One the crystals obtained in hexane and one obtains 7 of propanol in the form of white Instantaneous melting point As far as is this compound is not described in the The propane used as starting product can be obtained as To a solution of of caustic potash in 92 of one adds of then of oxy propane and one agitates for 4 hours One the e by concentration under one distills the residue and one obtains of epoxy propane in the form of a colourless Boiling point under Calculated 7 Found As far as is this compound is not described in the 2 One dissolves 7 of in 100 of ether one adds hydrochloric One the crystals thus formed and recrystallizes them in One obtains of hydrochloride in the form of white Melting point by scope heated Calculated Ci Found As far as is this compound is not described in the EXAMPLE Sy operating as in example 1 but using of secondary butylamine one obtains by distilla a product which crystallizes on point under One Instantaneous point 6 As far as is this compound is not described in the 4 1 y1 c1o ol By operating as in example 2 but using 8 of propanol one obtains after recrystallizatio in benzene of hydrochloride in the form of white Melting point by microscope Calculated Pound As far as is this compound is not described in the By operating as in example 1 but 17 of tertiary butylamine one obtains by distillation of in the form of a less Boiling point under As far as is this compound is not described in the EXAMPLE 6 hydrochloride By operating in example 2 but using of one obtains after recrystallization in benzene point with heated Calculated 7 Pound As as is this compound is not described in the 1 By operating as in example 1 but using 5 diethylamine one obtains by distillation 9 in the form of a colourless Boiling point under As far as is this compound is not described in the 1 cyclohexylsulphamate One dissolves of in 880 of anhydrous ether and one adds this solution to 3 of cyclohexylsulphamic acid dissolved in 55 of One the crystals thus formed and one recrystallizes them in One obtains of cyclohexylsulphaaate in the form of white Melting point 102 by microscope Analysis S Calculated 59 8 6 3 7 3 Found 59 7 8 o r oy n o y6roxy diethyl ethyl iodide dissolves of in 100 of anhydrous one adds of iodide and one leaves at rest for 48 hours at One ilters the crystals thus formed and one recrystallizes them in a mixture of ethyl acetate and One obtains of diethyl ammonium iodide in the form of white Melting point by microscope heated Analysis Calculated 7 31 3 7 31 As far as is this compound is not described in the 10 lamino By operating as in example 1 but using 20 of crude 2 propane and 11 of one obtains by distillation 13 of a product which crystallises on Boiling point under 0 One recrystallizes the crystals thus obtained in hexane and one obtains 12 of cyclopropylphenoxy in the form of white Instantaneous melting point As far as is this compound is not described in the The 2 ane potash in of one adds l of then of propane and one agitates for 20 hours at ambient temperature under a current of extracts the oil thus means of ether and one dries the ethereal phase on sodium One eliminates the ether by concentration under reduced One obtains 20 of propane in the of a colourless As far as is this compound is not described in the 11 hydrochloride By operating as in example 2 but using 11 of one obtains after recrystallization in benzene hydrochloride in the of white point by microscope with heated Analysis Calculated Found As far as is this compound is not described in the 12 By operating as in example 1 but 3 of one obtains by distillation of as is this is not described in the 1 c 1 By operating as in example 8 but using of one obtains after recrystallization in benzene of in the form of white point by scope 9 Calculated Found As far as is this compound is not described in the EXAMPLE One has prepared tablets corresponding to the hydrochloride 10 Excipient to 1 tablet of the EXAMPLE One has prepared tablets corresponding to the hydrochloride 40 to 1 25 of the magnesium 40 to 1 of the EXA One has produced injectable preparations corresponding to the hydrochloride 2 Aqueous solvent insufficientOCRQuality

Claims (9)

WHAT IS CLAIMED IS :

1. The derivatives of 1 -amino 3-phenoxy 2-propanol of general formula: in which Ar represents an ortho-c clopropylphenyl or para— cyclopropylphenyl radical, and R^ and R2 represent a hydrogen atom, a straight- chain or branched-chain alk l radical containing up 5 carbon atoms or a cycloalkyl radical containing from 3 to 7 carbon atoms, at least one of the radicals R-^ or R2 not being hydrogen, ' as well as their therapeutically compatible mineral or organic acid or quaternary ammonium salts.

2. 1-isopropylamino 3-(o-cyclopropylphenoxy) 2-propanol and its hydrochloride.

3. l-(s-butylamino) 3-(o-cyclopropylphenoxy) 2-propanol and its hydrochloride. ■

4. l-(t-butylamino) 3^(o-cyclopropylphenoxy) 2-propanol and its hydrochloride.

5. 1-diethylamino 3-(o-cyclopropylphenoxy) 2-propanol and its cyclohexylsulphauiate .

6. [ 3-(o-cyclopropylphenoxy) 2-hydroxy propyl] diethyl methyl ammonium iodide.

7. 1-isopropylamino 3-(p-cyclopropylphenoxy) 2-propanol and its hydrochloride.

8. 1-cyclopropylamino 3-(o-cyclopropylphenoxy) 2-propanol and its cyclohexylsulphauiate.

9. Irocess for preparing the products according to claim 1, 35378/2 in which Rj_ and Rg ave the meaning already indicated, is made to react with an epoxide of formula in which AT has the meaning already indicated, and, if desired, the resulting compound is made to react with a therapeutically compatible mineral or organic acid or a quaternizing agent to form the desired salt* Pharmaceutical compositions containing as active principle at least one compound according to claim 1 and a pharmaceutical vehicle*