Patent GB-966849-A (GB)
Title: Thiosemicarbazones and their preparation
Inventor: BARRETT PAUL ANTHONY
Filed: 1959-09-15
Abstract: The invention comprises a -dithiosemicarbazones of the general formula: <FORM:0966849/C1/1> wherein R3 and R4 are the same or different and each is a hydrogen atom, or is a straight or branched alkyl group of 1-10 carbon atoms, provided that when both R3 and R4 are alkyl groups the total in the two groups is 2-12 carbon atoms and optionally carrying a terminal hydroxy or carboxy group, or is a phenyl or benzyl group wherein the phenyl ring optionally carries one or more halogen atoms or hydroxy, alkyl, alkoxy, amino, alkylamino, dialkylamino, carboxy or alkoxycarbonyl or is a 2-thienyl, 2-thenyl, 2-furyl, 2-furfuryl group wherein the ring optionally carries one or more substituents each of which is an alkyl group or a halogen atom, or R3-C.C-R4 is a cyclopentane, -hexane or -heptane ring optionally carries a fused benzene ring, and either ring optionally carries one or more alkyl groups; and X1 and X2 are the same or different and each is a hydrogen atom, or is a straight or branched, saturated or unsaturated alkyl group having 1-6 carbon atoms and optionally carries a hydroxy or alkoxy group (the groups "alkyl" and "alkoxy" in the definitions of R3, R4, X1 and X2 containing 1-4 carbon atoms unless otherwise stated); other than glyoxal-, methylglyoxal-, ethylglyoxal- and phenylglyoxaldithiosemi carbazone, butane-, pentane-, hexane-, heptane-, 3-phenylpropane- and 4-phenylbutane-2, 3-dione-dithiosemicarbazone, benzil-, p, p1-dihydroxy benzil- and p, p1 -dimethoxybenzildithiosemicarbazone, glyoxal- and hydroxymethyl glyoxal -di- (4-methyl-, 4-ethyl- and 4-allyl-thiosemicarbazone) and propane-, and butane- and octane-2, 3-dione-di-(4 -methylthiosemicarbazone); the preparation thereof by reacting in an acid or neutral medium two molecular proportions of a thiosemicarbazide with an a -diketone, a -isonitrosoketone or a -dioxime or one molecular proportion of a thiosemicarbazide with an a -keto mono thiosemicarbazone or a -isonitroso mono thiosemicarbazone; and pharmaceutical compositions containing the known and novel thiosemicarbazones of the above general formula (see Division A5). 4-b -Hydroxyethylsemicarbazide is prepared by reacting acetophenone with methyl dithiocarbazinate to give acetophenone methyldithiocarbazinate and reacting the latter with b -hydroxyethylamine and hydrolysing the product with acid. 4-Methoxymethyl- and 4-b -methoxyethyl-thiosemicarbazide are prepared by reacting methoxy methyl- or b -methoxy ethyl-isothiocyanate with hydrazine.  5-Isonitroso-undecan -6- one is prepared by reacting di-n-amyl ketone with amyl nitrite. Similarly are prepared isonitroso ketones of the formula R3C:(NOH)COR4 where R3 and R4 are given as methyl and p-dimethylaminophenyl; iso-propyl and isobutyl; isopropyl and p-dimethylamino phenyl; methyl and p-amino-phenyl; b -carboxyethyl and phenyl; g -carboxypropyl and p-dimethylaminophenyl; methyl and p-carboxyphenyl; methyl and 5-chloro -2- thienyl; methyl and 2-furyl; 2-isonitroso -4- methylcyclohexane-1- one and 2-isonitrosoindane -1- one.ALSO:Pharmaceutical compositions useful in the treatment against Trichomonas vaginalis comprise, as active ingredient, an a -dithiosemicarbazone of the formula <FORM:0966849/A5-A6/1> wherein R3 and R4 are the same or different and each is a hydrogen atom, or is a straight or branched alkyl group having from one to ten carbon atoms, provided that when R3 and R4 are both alkyl groups the total in the two groups is from two to twelve carbon atoms, and optionally carrying a terminal hydroxy or carboxy group, or is a phenyl or benzyl group wherein the phenyl ring optionally carries one or more substituents, each of which is a halogen atom or a hydroxy, alkyl, alkoxy, amino, alkylamino, dialkylamino, carboxy or alkoxy-carbonyl, or is a 2-thienyl, 2-thenyl, 2-furyl, or 2-furfuryl group wherein the ring optionally carries one or more substituents, each of which is a halogen atom or an alkyl group, or R3-C-C-R4 is a cyclo-pentane, -hexane, or -heptane ring optionally carrying a fused benzene ring, and either ring optionally carries one or more alkyl groups; and X1 and X2 are the same or different and each is a hydrogen atom, or a straight or branched, saturated or unsaturated alkyl group having one to six carbon atoms and optionally carrying a hydroxy or alkoxy group (the groups "alkyl" and "alkoxy" in R13R14X1 and X2 containing one to four carbon atoms except where otherwise stated) together with an acceptable carrier.  Acceptable carriers do not include unsterilized water, saline solutions nor organic solvents which are normally used in organic chemistry for the preparation of compounds, nor culture mediums which contain metabolites and are normally used in pharmacological research, nor a non-ionic surface-active dispersing agent alone.  The compositions may be formulated as tablets, powders, granules, capsules, sachets, suspensions, emulsions, injection solutions or suspensions, extemporaneous injection solutions, pessaries or ointments.