IL37431A - Pharmaceutical compositions containing derivatives of thiazolino(3,2-a)pyrimidin-5-one,certain such novel derivatives and their preparation - Google Patents

Description

ft Pharmaceutical compositions containiag derivatives of certain novel derivatives and r invention relates to particularly analgesic compositions as active a of the general formula illustrated in 1 of the accompanying in hydrogen or an alkyl and A is a phenyl group optionally substituted with alkoxy or triflusromethyl or a or alkyl or a pharmaceutically acceptable acid addition salt the compounds of formula are optionally further suhstituted at positions 2 3 one at most positions or is suhstituted in addition to position I should he noted that when a suhstltuent is present at the compounds may exist in the form of stereoisomers and the invention includes both the forms and the active the preceding the alkyl and alkoxy groups are advantageously lover groups of these in particular containing from 1 to 4 compounds of formula herein are novel except those in which s and are each hydrogen and A is a methyl or a phenyl grou and and are each hydrogen and and are each a methyl To prepare compounds a process illustrated in 2 of the accompanying and which is also included within the scope of the may he Shis process comprises condensing a in vhich R and have the vith a ester of the in and A have the and B is a lover alkyl and then optionally salifying resulting compound may be used in free or salt In the latter the is released in situ by an alkaline This condensation is advantageously conducted vithin an organic solvent such as xylene or It is ted by for example at the refluxing temperature of the condensation may also be carried out vithout a by heating the mixture to The folloving examples illustrate the invention limiting Example I Synthesis of A R R2 Code Into a 1 litre flask fitted vith a stirring a cooler and a heatin are added 100 g dine R R2 and 300 ml The mixture is heated until it is and 190 g ethyl A B are then added After re luxing 5 the reaction mixture is left aside overnight at room The resulting talline material is suction washed with ethanol and then recrystallized from ethyl ether after which it is dried in vacuo to give g of Analysis Total nitrogen Calculated Found The resulting base may be converted to the as 20 g are dissolved in 130 ml at room 40 ml of 6N hydrochloric acid in ethanol solution are then with The mixture rapidly sets to a It is left aside during one hour at room and then one hour in an It is then suction washed once with chloroform and then twice with absolute after which it is dried in an oven at to give 22 g of 3 Calculated Found Total nitrogen Ionized chlorine Example II Alternative synthesis of A Code is dissolved in ethyl with The reaction mixture is then to incipient boiling vhich is maintained for a few The resulting orange solution is poured over 50 g It is then stirred during 15 A yellow product precipitates It is filtered and washed with The insoluble is taken up into an by washed with ether and dried in to give g of crystalline depression on admixture with the product obtained according to the procedure of Example Analysis Calculated Found Basic nitrogen Example III Preparation of A R 2 HjCode and acetate A B are mixed with xylene The reaction mixture is refluxed 7 After allowing to overnight at room a crude material is collected and is then recrystallized from chloroform to give g of Calculated Found Total nitrogen Example IV Preparation of A R Code To a are added R and ethyl benzoylacetate A C B vhich are dissolved in The mixture is vith 6 hours and is then left aside overnight at room The sulting material is vashed three times with suction filtered and then recrystallized from 100 ml to give 16 g of Analysist Calculated Found Total nitroge Example V Preparation of I t A 3 Code and ethyl A B ne and are then refluxed at room the ting crystals are suction vashed with xylene and vith On recrystallization from g of are Calculated Found Total nitrogen The constitution and physical properties of compounds obtained according to the examples described above and of othe compounds prepared in a similar manner are summarized in the following In this Table are also reported data relating to the analgesic activity of compounds as determined by one of the conventional testing procedures for this the Mice are given a single intraperitoneal injection of ml of 6 acetic acid The compound to be tested is administered orally at a dosage of one prior to the acetic acid The number of tic vrithing movements induced by pain is counted during the 15 minutes that follow the acetic acid The magnitude of the action of each compound described is expressed using one to four representing maximum r The analgesic activity of compounds permits their tion in human said compounds being administrable by the parenteral or rectal route at a daily dosage regimen generally comprised between 300 and 900 For such the compounds are formulated as therapeutical compositions with the vehicles or excipients suitable for these various routes of The formulated in unit dosage such as sitories and contain preferably from 100 to 300 mg of compound insufficientOCRQuality

Claims (1)

1. 0 particular compositions comprising a of the general formula in which and are each hydrogen or an alkyl and A a phenyl optionally substituted with or trifluoromethyl or a methyl or or an acid addition salt together a pharmaceutically acceptable of formula I in Claim provided when and then A is not a methyl or a phenyl and when and are each hydrogen and is a methyl then is not a methyl and their addition Compounds as claimed in wherein the alkyl and alkoxy groups are lower groups of this Compounds as claimed in Claim 2 or wherein one at most of substituents and is than and its r 10a 6 its and its 3 and its and its and its 11 a and its tolvl and its and its and its and its salts 3 and its and its and its and its 5 and its and its and its 3 232 and its and its and its Process for the preparation of compounds as claimed in 2 claims comprising condensing a of the formula in R and have the with a ester of the in and Λ have the and B is a lower alkyl then optionally salifying the resulting Process as claimed in claim the lidine is used ee salt in the latter case the imine being released situ by an Process as claimed in claim wherein the condensation is conducted in an organic solvent Process as claimed claim wherein the condensation is conducted without by heating the mixture of reagents to Process for the preparation of compounds as claimed in 2 claims substantially as described with reference to the insufficientOCRQuality