GB1065964A - Substituted carbamyl aminotriazoles,their preparation and compositions containing them - Google Patents

Abstract

The invention comprises triazoles having a tertiary carbamyl (including thiocarbamyl and amidino) group on nuclear nitrogen, and an amino or substituted amino group or a group hydrolysable thereto on at least one of the ring carbons; e.g. the compounds of formula <FORM:1065964/C2/1> <FORM:1065964/C2/2> <FORM:1065964/C2/3> <FORM:1065964/C2/4> where X is O, S or NR3 (R3 being C1- 6 acyclic hydrocarbon); R1 and R2 are hydrocarbon or oxygen-interrupted hydrocarbon groups free from aliphatic unsaturation and having up to 12 carbon atoms, or R1 and R2 together with the nitrogen form a heterocyclic ring, which may be multicyclic, having up to 12 carbon atoms; and at least one of R4 and R5 is amino, substituted amino, or a group hydrolysable thereto (e.g. amino, hydrocarbylamino, dihydrocarbylamino, acylamino (including sulphonic acyl), diacylamino, benzalamino, halobenzalamino, nitrobenzalamino, dialkylaminobenzalamino, alkoxybenzalamino, alkylenedioxybenzalamino, carboxybenzalamino or naphthalamino), any remaining R4 and R5 being hydrogen, halogen, hydrocarbon, amido, or hydrocarbon having one or two separated oxygen or sulphur atoms (e.g. hydrocarbyloxy, hydrocarbyloxycarbonyl, carboxy, or hydrocarbylthio). These compounds can be prepared by (1) reacting a suitable aminotriazole or N-alkali metal derivative thereof with an N - disubstituted carbamyl or thiocarbamyl halide or haloformamidine; (2) (for carbamyl and thiocarbamyl compounds) reacting a suitable aminotriazole with phosgene or thiophosgene to give the aminotriazole carbonyl or thiocarbonyl halide, and reacting this with an excess of a secondary amine; or (3) (for amidino compounds) reacting a dialkyl carbamyl or thiocarbamyl compound with a strong halogenating agent, e.g. POCl3 + PCl5, to give the corresponding dichlorodialkylaminomethyltriazole, and reacting this with a primary alkylamine to give the N,N,N1-trialkylamidinotriazole nuclearly substituted with amino. Other reactions producing compounds as defined are also referred to. Isomeric mixtures of products may be obtained. Many examples of compounds of the invention are given. The compounds of the invention are of value as medicinals (see Division A5). Starting materials.-3- (or 5-) p-Chlorobenzalamino - 1,2,4 - (1H) - triazole is prepared from p-chlorobenzaldehyde and 3-amino-1,2,4-(1H)-triazole. Similarly prepared are compounds in which the benzene ring is substituted by p-nitro, p-dimethylamino, p-methoxy, 2,4 - dimethoxy, 3,4 - methylenedioxy, and o-carboxy. 3-Acylamino-1,2,4-triazoles are obtained from 3-aminotriazole and acetic, butyric, benzoic or propionic acid anhydrides. 3- (or 5-)-Succinimido-1,2,4-triazole is prepared from 3-aminotriazole and succinic anhydride. 3-Dimethylamino-1,2,4-triazole is prepared from dimethylcyanamide and formhydrazide at 140 DEG C. 3,5 - Bis - p - dimethylaminobenzalamino- 1,2,4-triazole is obtained from 3,5-diaminotriazole and p-dimethylaminobenzaldehyde. 3-p-Toluenesulphonamido-1,2,4-triazole is made from 3-aminotriazole and tosyl chloride. 3 - Acetamido - 1,2,4 - triazolyl - 1 - carbonyl chloride is obtained from 3-acetamidotriazole and phosgene. Reacting dimethylcyanamide with EtCON HNH2 or MeOCONHNH2 produces 3(5)-di-methylamino - 5(3) - ethyl or - methoxy-1,2,4-triazole. Other compounds.-The 2,4 - dinitrophenyl-hydrazone of p-anisaldehyde and p-dimethylaminobenzaldehyde are obtained from 2,4-dinitrophenylhydrazine and 1-dimethylcarbamyl - 3 - p - methoxybenzalamino - 1,2,4-triazole and 1-(1-pyrrolidinecarbonyl)-3-p-dimethylaminobenzalamino - 1,2,4 - triazole respectively. Triethylamine trifluoroacetate is obtained as by-product in a reaction involving triethylamine, trifluoroacetic anhydride and 1-dimethyl-carbamyl-3-amino -1,2,4-triazole.ALSO:Pharmaceutical compositions comprise a triazole having a tertiary carbomyl (including thiocarbamyl and amidino) group or nuclear nitrogen, and an amino or substituted amino group or a group hydrolysable thereto, on at least one of the ring carbons (see Division C2), together with a non-toxic pharmaceutical carrier therefor. Many active ingredients and carriers are given. Other active compounds, such as vitamins, pain killers, tranquilisers, antibiotics and antitussive agents may also be present. The triazole compounds are of value as analgesics and anti-inflammatory agents, and the compositions may be administered orally, parenterally or by other methods, as solutions, suspensions, syrups, elixirs, tablets, capsules or powders.