DE2126304B2 - 1-AcyIthiosemicarbazide substituted in 4-control, process for their preparation and pharmaceuticals containing them - Google Patents

Description

4 ^r i

So far, virustatically effective derivatives of thiosemicarbazide are only in the form of thiosemicarbazones des isatin (marborane) known. i-Acyl-4-allylthiosemicarbazide are by G a g i u et al., j. pr. Ch. 36, p. 108 (1967), from carboxylic acid hydrazides and allylisothiocya- ■ » nat synthesized as a precursor for 1,3,4-thiadiazoles, a therapeutic effect of these 1-acylthiosemicarbazides is not proven. Turberculostatics are also described, including l- (2-hydroxybenzoyl) -4-n-butylthiosemicarbazide by M. H. S h a h, J. Sei. Ind. Resewi arch 190, 68-70 (1960), as well as, inter alia, l-benzoyl-4-naphthyl- (l) -thiosemicarbazide von Buu-Hoi (Bull. Soc. chim. France 1956, pp. 363-9).

The invention aims at expanding this class to open up new fields of application t, ^r> before these compounds.

It has been found that the aliphatic and aromatic isothiocyanates with Carbonsäurehydrazi1 - Adamantoyl- (1 J ^ -cyclohexylthiosemicarbazid,
F. 234 ° C, 89%

2.4

l-cinnamoyl-4-n-butylthiosemicarbazide,
F. 169 ° C, 64%

1-adamantoyl- (1) -4-n-butylthiosemicarbazide,
195 ° C, 79%

1- (4-chlorophenoxyacetyl) -4-n-butylthiosemicarbazide,
F. 165 ° C, 82%

l-adamantoyl- (l) -4-phenylthiosemicarbazide,
F. 182 ° C, 38%

i-cinnamoyl-4-cyclohexylthiosemicarbazide,
F.202 to 204 ° C, 81%

2.9

1- (4-chlorophenoxyacetyl) -4-cyclohexylthiosemicarbazide, m.p. 187 to 188 ° C, 83%

2.10

1- (4-nitrobenzoyl) -4-phenylthioseniicarbazide,
F. 164 to 66 ° C, 88 ° /.)

Claims (10)

Patent claims: 1. 1-Acylthiosemicarbazides substituted in the 4-position of the general fjrmel R ¹ -C-NH-NH-C-NH-R ² Il Il ο s in the Ri = 4-nitrophenyl-, styryl-, adamantyl- (l) -, 4-chloro-phenoxymethyl- or carbethoxy- and R ² = phenyl-, cyclohexyl- or η-butyl- can be, where for the case that R ¹ = styryl-, R ² only stands for cyclohexyl- or η-butyl-, and for the case that R ¹ = carbethoxy-, R ^{2 stands} for phenyl 2. Process for the preparation of 1-acylthiosemicarbazides according to claim 1, characterized in that carboxylic acid chlorides of the general formula are used in a manner known per se R ¹ -C Cl Il ο in which R ^{1 has} the meaning given, with thiosemicarbazides of the general formula H ₂ N-NH-C-NH-R ² in which R ^{2 has} the meaning given, or by using carboxylic acid hydrazides of the general formula R ¹ -C-NH-NH ₂ in which R ^{1 has} the meaning given, with isothiocyanates of the general formula S = C = NR ² in which R ^{2 has} the meaning given, converts. 3. Medicinal products containing 1-acylthiosemicarbazide according to claim 1 in a mixture with pharmaceutically acceptable carriers and auxiliaries. thiosemicarbazides substituted in the 4-position with carboxylic acid chlorides in a manner known per se to new 4-substituted 1-acylthiosemicarbazides have it implemented. These connections show sur- - :. seeing virustatic effectiveness Example 1.0 6.6 g (0.05 mol) of ethyl oxalate monohydrazide are dissolved warm in as little ethanol as possible and in with stirring 7.5 g (0.055 mol) of phenyl isothiocyanate, im dissolved in the same volume of ethanol, added dropwise Precipitation occurs for a short time. It is heated under reflux for a further 1 hour, filtered off with suction after cooling and off Recrystallized ethanol. ^|? Yield of 1-carbethoxycarbonyl-4-phenylthiosemicarbazide 11.5 g = 88%; 153-54 ° C. Example 2.1 10 g (0.058 mol) of 4-CycIohexylthiosemicarbazid are ^{Dissolved 2} "den in 60 ml of warm chloroform and 11.9 g (0.064 mol) of 4-nitro-benzoyl chloride dissolved in 30 ml of chloroform added dropwise with stirring. The mixture is heated under reflux for a further 3 hours, with slight evolution of HCl. After cooling is sucked off and off - ^r > acetic acid recrystallized. Yield of 1- ^ - nitrobenzoyl ^ -cyclohexylthiosemicarbazide 13 g = 40%; F. 203 ⁰ C. Analogously to Examples 1.0 and 2.1, the following 1-acylthiosemicarbazides, substituted in the 4-position iii, were obtained the corresponding isothiocyanates and carboxylic acid hydrazides or from 4-substituted thiosemicarbazides and acid chlorides. 2.2 l- (4-chlorophenoxyacetyl) -4-phenylthiosemicarbazide,
192 ° C, 91% 40