IL24812A - Pyrido(2,3-d)pyrimidines - Google Patents

Description

d lovel his relates to novel midine According to the present invention are provided derivatives of formula or pharmaceutically acceptable salts in which and are the same or different and each is nitro or an or an optionally or halogen substituted phenyl or compound of formula Ϊ may be prepared by any known method and in particular from corresponding of the formula by reacting the latter with She reaction is preferably carried out with heating in the presence of an inert liquid medium which acts as a solvent for the and preferably under In common with previously described derivatives9 the compounds of the present invention possess selective antimicrobial activities which render useful as topical antibacterials and the systemic treatment of bacterial Β In an important class of the 2 derivatives of formula I possess diuretic activity and are particularly valuable for the fact that diuresis is produced experimental animals with an increased of sodium to potassium ions in the thereby conserving potassium ion and making unnecessary the concomitant administration of potassium furthermore they do not adversely affect the clearance of uric acid as do some other diuretic Especially embraced within this class of compounds having diuretic activity are those of formula I in which gen atom or a methyl or ethyl group and It the said alkyl and alkoxy groups each having from 1 to carbon The preferred compound of formula I is or pharmaceutically acceptable salts Tests in standard experimental animals suggest that the compounds of the present invention would exhibit diuretic properties in human beings when administered in doses of the order of of body The compounds of formula I are preferably administered in pharmaceutical preparations as tablets and solutions of ceutically acceptable salts by oral or parenteral routes for any of the indications which diuretic agents are commonly The present invention in one aspect comprises a compound of the formula I as hereinbefore or a pharmaceutically acceptable salt In another aspect it comprises a method for the preparation of the compounds of formula I or pharmaceutically acceptable salts thereof by amination of the corresponding pyrimidine In a further aspect it comprises a pharmaceutical preparation comprising a compound of formula I or a acceptable salt thereof as active ingredient in admixture with a The following illustrate the present Example 1 of pyrimidine and 150 of a saturated solution of ammonia in absolute ethanol were placed in a steel and heated at for 20 The was the content s and the precipitate washed well It was then recrystallised ethanol to yield 1 0 of white hydrochloride half Example 2 By the method of 1 of crude heated with 150 a saturated solution of in absolute alcohol at for hours to yield of the recrystallised hydrochloride hydrate of the product 3 3y the method described in Example 1 of 2 gave recrystallisation of the product from aqueous ethanol which was acidified hydrochloric of 2 hydrochloride melting at 3 4 2 2 mixture of 174 of ethyl and 1 of in 900 of ether was heated with at for was allowed to i mixture then cooled to and 300 B methanol This mixture was filtered and the precipitate washed with The precipitate was then stirred with 2 litres of boiling refiltered and washed with hot On 115 of was 57 of the above 7 compound was placed in 400 of chloroform and of was To this was with of thionyl chloride while keeping the temperature of the mixture below Then the mixture was heated at with for The resulting solution was o centrated in vacuo at to a thick The syrup was dissolved in 200 of absolute ethanol and this solution was made basic by the slow with vigorous of concentrated aqueous The resulting mixture was held at for 18 hours and then The precipitate was stirred for one hour of 2N sodium hydroxide filtered and washed with On of was 2 A solution of anhydrous ethanol saturated with ammonia at was A mixture of 100 of this solution and 20 of the above compound was heated in a steel bomb for 8 hours at The bomb was then cooled and the contents The precipitate was dissolved in 400 of boiling 75 per cent aqueous ethanol made acidic with hydrochloric the solution treated with filtered while and The precipitate so formed was filtered and dried to give 1 of hydrochloride Example 5 By the method described in Example of hydrochloride hydrate was obtained from of Example By the method described in Example of ine hydrochloride hydrate obtained from of Example 2 hydrochloride was obtained from of 2 By the described in Example hydrochloride was obtained 20 of lo lpy 4 By the method described in Example of hydrochloride dihydrate was obtained from of 2 pyrido 2 4 By the method described in Example of hydrochloride hemihydrate was obtained from 20 of 2 11 2 By the method described in Example of Jpyrimidine hydrochloride hydrate was obtained from 20 of aethylpy ido pyr e 12 2 2 By the method described in Example of lpy ido 2 hydrochloride hydrate was obtained from 20 of phenyl 2 Example g of Example dissolved in 50 ml of and g powdered was added with stirring at room e reaction mixture was heated oa a bath for 24 cooled poured a mixture of 200 ml of ethanol and 200 sal of aisture was made basic by and the precipitate filtered aad precipitate was from had been made acid by addition of of sulfate following of from 355 insufficientOCRQuality

Claims (1)

1. CLAIMS compounds of the formula or pharmaceutically acceptable salts in which and or and each is a hydrogen or nitro an or an Optionally halogen substituted phenyl o benzyl A compound according to Claim 1 or a pharmaceutically acceptable salt in which E 1 is an unsubstituted phenyl group or a phenyl group substituted with one or halogen or nitro groups and is a hydrogen atom or a methyl or the said and groups each having from 1 to 4 carbon h A pharmaceutically acceptable salt of any of the compounds claimed in Claims 3 to pharmaceutically acceptable salt according to 1β being the pyrimidine y derivatives according to Claim substantially as described in 1 to 13 A method of preparing compound of the formula I in Claim 1 wherein a compound of the formula in and have the as in Claim 1 is reacted with A method according to Claim 20 for preparing 2 h or a ceutically acceptable salt wherein is reacted with A method according to Claim 20 wherein the reaction is carried out under pressure and in the presence of an inert liquid medium as a solvent for the A of preparing derivatives according to Claim 1 substantially as described in Examples 1 to 14 A pharmaceutical preparation comprising as an ingredient a compound according to any of Claims 1 to 15 or a salt thereof according to Claims 16 to A pharmaceutical preparation according to Claim 24 in the torn of a A preparation according to Claim 24 or 25 in active ingredient is insufficientOCRQuality