Patent GB-971176-A (GB)
Title: Thiazolidone derivatives
Inventor: CLARKSON RICHARD
IPC: C07D277/34
Filed: 1961-11-09
Abstract: The invention comprises compounds of general formula <FORM:0971176/C1/1> wherein: R1 stands for the radical -COX, wherein X stands for a hydroxy, alkoxy, alkenyloxy, alkoxyalkoxy, aralkoxy or an alkylthio radical; wherein R2 stands for hydrogen, an alkyl radical or a radical -COX1, wherein X1 has the same scope as X but X and X1 may be the same or different; and wherein R3 and R4, which may be the same or different, stand for hydrogen or for alkyl radicals: and the processes for their preparation (1) by reacting a nitrile R1R2CH.CN with a thiol HS.CR3R4. COOR5 wherein R5 is hydrogen or an alkyl (1-4C) radical, (2) by reacting a thioamide R1R2CH.CSNH2 with a compound Y.CR3R4.COOH, wherein Y is chlorine, bromine or iodine, or an ester or acid halide thereof, and (3) when R1 is carboxy by reacting corresponding compounds wherein R1, but not R2, is t-butoxycarbonyl with an acid.  Ethyl- and n-butyl-thiocarbonylacetonitrile are obtained by reacting ethyl- and butyl-mercaptans with cyanacetylchloride and dimethylaniline.  The Provisional Specification relates to compounds of general formula <FORM:0971176/C1/2> and their tautomers, wherein: R1 is cyano or -COX or -CSX, where X is hydroxy alkoxy, cycloalkoxy, aryloxy, aralkoxy, thiol, alkylthio, cycloalkylthio, arylthio, aralkylthio, amino, mono- or di-substituted amino or a hydrocarbon radical; R2 is hydrogen, alkyl, cycloalkyl, alkenyl, aryl, aralkyl, cyano or -COX1 or -CSX1, where X1 is defined as is X; and R3, R4 and R5 are hydrogen or hydrocarbon radicals.  N-Alkyl derivatives of the tautomeric form of these compounds of formula <FORM:0971176/C1/3> wherein R6 has the meaning given for R2 or R3 and R7 is alkyl, are included.  The processes comprise (1) reaction of compounds R1R2R3C.CN and HS.CR4R5.COOR8 (R8 is hydrogen or hydrocarbon), (2) reaction of compounds R1R2R3C.CSNH2 and Y.CR4R5.COOH (Y is chlorine, bromine or iodine) or an ester or acid halide thereof, and (3) alkylation of compounds having R2 or R3 or both hydrogen to give N-alkyl derivatives.  Additional compounds prepared are 2-carbamoylmethylthiazol-4-one by heating cyanacetamide and thioglycollic acid with pyridine, and 2-ethoxycarbonylmethylene-3-methylthiazolid-4-one by reacting dimethyl sulphate with 2-ethoxycarbonylmethylthiazol-4-one in sodium hydroxide solution.ALSO:Pharmaceutical compositions comprise, in admixture with pharmaceutically-acceptable diluents or carriers, thiazolidones of general formula <FORM:0971176/A5-A6/1> wherein R1 stands for the radical -COX, wherein X stands for a hydroxy, alkoxy, alkenyloxy, alkoxyalkoxy, aralkoxy or an alkylthio radical; wherein R2 stands for hydrogen, an alkyl radical or a radical -COX1, wherein X1 has the same scope as X but X and X1 may be the same or different; and wherein R3 and R4 which may be the same or different, stand for hydrogen or for alkyl radicals.  Oral, parenteral and topical administration (as tablets, pills, capsules, solutions, suspensions, creams, lotions and ointments) are mentioned.  The compounds are antiallergic and anti-inflammatory.  Known anti-inflammatory agents (e.g. acetylsalicyclic acid, phenylbutazone, cortisone, hydrocortisone) may be incorporated.  The Provisional Specification relates to such compositions incorporating compounds of general formula <FORM:0971176/A5-A6/2> and their tautomers, wherein: R1 is cyano or ..COX or -CSX, where X is hydroxy, alkoxy, cycloalkoxy, aryloxy, aralkoxy, thiol, alkylthis, cycloalkylthio, arylthio, aralkylthio, amino, mono- or di-substituted amino or a hydrocarbon radical; R2 is hydrogen, alkyl, cycloalkyl, alkenyl, aryl, aralkyl, cyano or -COX1 or -CSX1 where X1 is defined as is X; and R3, R4 and R5 are hydrogen or hydrocarbon radicals.  N-alkyl derivatives of the tautomeric form of these compounds of formula <FORM:0971176/A5-A6/3> wherein R6 has the meaning given for R2 or R3 and R7 is alkyl, are included.  Additional compounds specified are 2-carbamoylmethylthiazol-4-one and 2-ethoxycarbonylmethylene-3-methylthiazolid-4-one.