GB1111957A - Improvements in or relating to anthelmintic compositions - Google Patents

Abstract

2-Amidobenzimidazole compounds of the structural formula <FORM:1111957/C2/1> wherein A is methyl or phenyl; X is oxygen or sulphur; R is hydrogen, alkyl of 1 to 10 carbon atoms, hydroxyalkyl of 1 to 10 carbon atoms, or benzyl; R1 is hydrogen, alkyl of 1 to 10 carbon atoms, or acyl of 1 to 10 carbon atoms; and Y and Z are hydrogen, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, trifluoromethyl, amino, alkylamino, dialkylamino, cyano, acylamino, halo, hydroxy, nitro, alkyl-thio, carboxy, carbalkoxy, carbamoyl, alkyl-carbamoyl, or dialkylcarbamoyl, all of the undefined alkyl groups having 1 to 4 carbon atoms, are prepared by condesing a 2-amino-benzimidazole with a compound of formula <FORM:1111957/C2/2> preferably in the presence of a base in a solvent, e.g. pyridines. Compounds of formula I in which Y or Z is amino are prepared of catalytic reduction of the corresponding nitro compound preferably using a palladium-on-carbon catalyst. Alternatively compounds of Formula I may be prepared by reacting the compound formed by reacting cyanamide with the selected carboxylic acid chloride in the presence of an acid-acceptor, e.g. pyridine or triethylamine, with an appropriately substituted o-phenylene diamine. Compounds in which X is sulphur may be prepared by reacting the corresponding compound in which X is oxygen with phosphorus pentasulphide, preferably in a solvent. The compounds of Formula I where R1 is alkyl and R is hydrogen are prepared by treating o-phenylene diamine with an alkyl isocyanate to form an alkyl o-aminophenylthiourea, which is cyclized to form a 2-alkylaminobenzimidazole, which is reacted with benzoyl or acetyl chloride to yield a 2-(N-alkylacylamino)benzimidazole. 1-Methyl-2-acetamidobenzimidazole and 2-(N,N-diacetylamino) - 1 - methylbenzimidazole are both prepared by the reaction of acetic anhydride with 1-methyl-2-aminobenzimidazole. Acid addition salts may be prepared in conventional manner.ALSO:Anthelmintic compositions comprise as active ingredient a 2-amidobenzidazole of the formula <FORM:1111957/A5-A6/1> wherein A is methyl or phenyl; X is oxygen or sulphur; R is hydrogen, alkyl or hydroxyalkyl of 1 to 10 carbon atoms or benzyl; R1 is hydrogen, alkyl or acyl of 1 to 10 carbon atoms; and Y and Z are hydrogen, alkyl or alkoxy of 1 to 10 carbon atoms, trifluoromethyl, amino, alkylamino, dialkylamino, cyano, acylamino, halo, hydroxy, nitro, alkylthio, carboxy, carbalkoxy, carbamoyl, alkylcarbamoyl or dialkylcarbamoyl, all of the undefined alkyl groups having 1 to 4 carbon atoms, or a pharmaceutically acceptable acid addition salt thereof, and a pharmaceutical carrier. The 2-amidobenzimidazole is preferably 2-benzamido-benzimidazole or 2-acetamidobenzimidazole and specified salts are the hydrochloride, hydrobromide, sulphate, phosphate, acetate or cyclohexylsulphamate. The compositions are administered orally in the form of an animal feed, drench or bolus, capsules, liquids or tablets which may be emperic coated or adapted for sustained release.