IL28628A - Benzhydryl aminopropanol ethers - Google Patents

Description

ethers This invention relates to therapeutically useful ethers and acid addition salts to processes for their preparation and to pharmaceutical compositions containing Hew benzhydryl aminopropanol ethers of the invention are those of the general formula OH wherein the various R symbols are the of different and each represents a hydrogen or halogen atom or an alkyl or fluoromethyl group and Q represents an alkyl with the proviso that when the R symbols all represent hydrogen atoms Q is not an alkyl of 1 to carbon acid addition salts By the term as used in t his specification is meant straight or branched chain alkyl groups having at most 6 carbon The ethers of formula I have valuable therapeutio properties they have and local anaesthetic some of these compounds show pronounced arrhythmic properties which those of while in which one or both of the phenyl rings carry at least one Compounds of formula I wherein sents an isopropyl group are of outstanding For the above the compounds of this invention may be administered orally or parenterally in such forms as injectables or the like by porating the appropriate dosage of the compound with ceutically acceptable carriers according to accepted ceutical The dosage for various mammalian species would be up to 100 administered orally or dependant upon the individual requirements of the The preferred dosage is from 5 to 25 Oral administration of such dosages is For use as therapeutics the compounds of formula I may be used as bases or as acid addition salts containing pharmaceutically acceptable the lactates and According to a feature of the the compoun of formula I are prepared by reacting a glycidyl ether of the general formula with an amine of the formula wherein the various symbols are as hereinbefore The reactants are tageously heated in a closed vessel a Carius preferably dissolved in an inert anhydrous such as toluene or A benzhydryl ether obtained by the aforementioned process may be converted into an acid addition salt by methods known per for by the action of an acid on the base in an appropriate for example an The compounds of formula II can be prepared by acting a benzhydryl halide of the general formula Hal represents a halogen atom and the other symbols are as hereinbefore with 2 IV 0 The reaction is preferably effected in an anhydrous inert organic such as diethyl ether or Another way to prepare the compounds of formula II is by condensing a benzhydryl derivative of the wherein M represents an alkali metal atom and the other symbols are as hereinbefore with 2 I 2 VI 0 The reaction is preferably effected by heating the in an inert organic such as an aromatic for example toluene or In still another the compounds of formula II are prepared by epoxidation of an appropriately substituted benzhydryl ether of the wherein the various symbols are as hereinbefore The epoxidation is carried out in manner known for example with perbenzoic acid in benzene solution at a temperature between 0 and The compounds of formula I or formula II may also be prepared by the application of other methods known se for the production of benzhydryl The following Examples illustrate the EXAMPLE 1 In a closed vessel a mixture of of isopropylamine and a solution of g of 1 in of anhydrous benzene is heated for 16 hours at After the mixture is treated with three portions of 20 of The benzene layer is separated and dried with sodium solvent is removed by By means of an electrometric titration there is determined how many equivalents of benzhydryl ether are whereupon an equivalent quantity of hydrogen chloride in diethyl ether is After crystallisation from there is obtained g of Yield melting point Calculated for C Q O 20 2o 2 Found The preparation of the benzhydryl glycidyl ether employed as starting material is described in the following EXAMPLE 2 A suspension is made of g of and g of sodium carbonate in 30 of anhydrous Precautions are taken that no moisture enters the The mixture is heated until the solvent boils under While 9 of is added to the refluxing After completion of the the mixture is stirred and kept refluxing for another 20 After cooling and the solvent is removed from the filtrate by After crystallisation from ether range there is obtained g of 1 Yield boiling point EXAMPLE 3 Following the general procedure described in Example 1 but substituting unsubstituted or different appropriately substituted benzhydryl glycidyl ethers for the the benzhydryl aminopropanol ethers of formula I as described below obtained in the form of their Analytical dataj EXAMPLE 4 Following the general procedure described in Example 2 but substituting unsubstituted or different appropriately stituted benzhydryl chlorides for the the benzhydryl glycidyl ethers conforming to formula II are preparations as active at least one of the therapeutically active compounds of general formula I or acid addition salt in association with a pharmacologically acceptable The preparations may take any of the forms customarily employed for administrat on of therapeutically but the preferred types are suitable for oral administration and especially pills and capsules including The tablets and pills may be formulated in the usual with one or more pharmacologicall diluents or for lactose or and include materials of a lubricating for example calcium Capsules made of absorbable such as may contain the activ substance alone or in i of 1 M for or n or bo up 1 a form suitable for or emulsion in sterile water or an organic liquid usually employed for injectable for example a vegetable oil such as olive oil or a sterile solution in an organic insufficientOCRQuality

Claims (1)

1. CLAIMS Benzhydryl aminopropanol ethers of general formula OH wherein the various R symbols are the same different and each represents a hydrogen or halogen atom or an alkyl or fluoromethyl group and represents an alkyl with the proviso that when the R symbols all represent hydrogen atoms Q is not an alkyl of 1 to 3 carbon and acid addition salts and acid addition salts and acid addition lts and acid addition salts ol and acid addition 9 6 Pharmaceutical compositions which as active ingredient a aminopropanol ether as claimed in any one of Claims or acid addition salt in association with a pharmaceutical 7 Process for the preparation of benzhydryl aminopropanol ethers of formula I in Claim which comprises reacting a hydryl halide of the general formula in which Hal represents a halogen atom and the re as defined in Claim with and reacting the glycidyl ether of the general thus formed with an amine of the formula wherein is as defined in Claim 8 Process for the preparation of benzhydryl aminopropanol ethers of formula I in Claim which comprises condensing a benzhydryl derivative of the general formula in which an alkali metal atom and the symbols E are as defined in Claim epiehlorohydrin and reacting the glycidyl ether of II in Claim thus with an amine of the formula wherein is as defined in Claim Process for the preparatio of ethers of in Claim which comprises epoxidation of a ether of the general wherein the various symbols are as defined in in a known per and reacting the ether of general formula II in Claim thus formed with the formula wherein is as defined in Claim 10 Process according Claim 9 wherein the epoxidation of a benshydryl ether of the formula VII is carried out with perbensoic acid in benzene solution at a temperature between 0 and For the insufficientOCRQuality