Patent GB-859316-A (GB)
Title: Improvements in or relating to substituted 3.5-dioxotetrahydro-1.2.6-thiadiazine-1.1-dioxides
IPC: A61K31/00
Filed: 1958-04-03
Abstract: The invention comprises compounds of general formula : <FORM:0859316/IV(b)/1> and their salts with inorganic and organic bases wherein R1 represents an aromatic or araliphatic hydrocarbon radical which can have halogen atoms, nitro groups or alkoxy groups as substituents, R2 represents a hydrogen atom or a hydrocarbon radical which can have halogen atoms, nitro groups or alkoxyl groups as substituents, R3 represents a hydrogen atom or a hydrocarbon radical which can have halogen atoms, hydroxyl, oxo, acylamino, carbalkoxy, or nitro groups as substituents and as chain or ring members can contain O, S, SO, SO2 or NH instead of methylene groups and - N = instead of methine groups and R4 represents a hydrogen atom or a hydrocarbon radical not aromatically bound but otherwise corresponding to the definition of R3, the preparation thereof by (a) reacting a malonic acid of the general formula : <FORM:0859316/IV(b)/2> or a reactive functional derivative thereof with a sulphamide of the general formula :  <FORM:0859316/IV(b)/3> or an N-acyl derivative thereof, if necessary in the presence of a basic or acid condensing agent and, if desired, converting the product provided at least one of the radicals R2, R3 p  and R4 represents a hydrogen atom, into a salt with an organic or inorganic base; (b) reacting, advantageously in the presence of a basic condensing agent, a reactive ester of an alcohol R41OH, where R41 has the same meaning as R4 with the exception of hydrogen, with a compound of the general formula :  <FORM:0859316/IV(b)/4> or a salt thereof; (c) condensing a compound of the general formula :  <FORM:0859316/IV(b)/5> with an oxo compound R411=O wherein R411 represents a geminate divalent hydrocarbon radical which can have halogen atoms, nitro groups or hydroxyl groups as substituents and can contain as ring or chain members O or NH instead of methylene radicals and - N = instead of methine groups, and simultaneously or subsequently reacting with catalytically activated hydrogen; (d) hydrogenating a compound of the invention which contains aliphatic multiple linkages in one or more of the radicals R1, R2, R3 and R4 by means of catalytically activated hydrogen to form a compound without or with only a reduced number of aliphatic double or triple bonds in the said radicals; a process for the preparation of compounds of the general formula : <FORM:0859316/IV(b)/6> wherein R5 and R6 represent hydrogen or hydrocarbon radicals, whereby the latter can be bound to each other direct or by way of an oxygen atom and can contain as substituents halogen atoms, hydroxyl or oxo groups and as chain or ring members O, S, SO, SO2 or NH instead of methylene groups and - N = instead of methine groups and R1, R2, R3 and R4 ar as defined above, wherein a compound of the general formula :  <FORM:0859316/IV(b)/7> is reacted with formaldehyde and a nitrogen compound of the general formula : <FORM:0859316/IV(b)/8> the reaction being performed either simultaneously or in any order desired; a process for the preparation of compounds of the general formula :  <FORM:0859316/IV(b)/9> wherein R11, R21 and R31 are identical with the radicals R1, R2 and R3 or differ therefrom but still fall within the definitions given for the latter radicals, which comprises reacting a hydroxy methyl compound of the general formula :  <FORM:0859316/IV(b)/100> with a compound of the general formula :  <FORM:0859316/IV(b)/111> and pharmaceutical solutions comprising a salt of a compound of the invention with at least one pharmacologically active pyrazolone compound (see Group VI), possibly together with other additives, dissolved in water. Aryl substituted sulphamides, R1 NH,SO2, NHR2, are prepared by reacting sodium salts of formarylides with sulphonyl chloride and reacting the chlorosulphonyl formarylides with ammonia or a primary amine.ALSO:Pharmaceutical solutions contain at least one pharmacologically active pyrazolone compound and a salt of a compound of the general formula <FORM:0859316/VI/1> (wherein R 1 represents an aromatic or araliphatic hydro carbon radical which can have halogen atoms, nitro groups or alkoxy groups as substituents, R 2 represents a hydrogen atom or a hydro carbon radical which can have halogen atoms, nitro groups, or alkoxy groups as substituents, R 3 represents a hydrogen atom or a hydro carbon [group] which can have halogen atoms, hydroxyl, oxo, acylamino, carbalkoxy, or nitro groups as substituents, and as chain or ring members can contain O, S, SO, SO2, or NH instead of methylene groups a -N = instead of methine groups and R 4 represents hydrogen or a hydro carbon not aromatically bound but otherwise corresponding to the definition of R 3) and possibly other additives, dissolved in water.  The pyrazolone may be 4-dimethyl amino-1-phenyl-2, 3-dimethylpyrazolone -(5).  The salts referred to above themselves have pharmacological prepared and may be administered parentically in aqueous solution for the treatment of rheumatism.