Anthelmintic amidines

Nitriles react with ammonia, or primary or secondary amines in the presence of an acid catalyst to give amidines (Scheme 26) (75, 77, 81). The catalysts used are hydrochloric acid and aluminium chloride. The amidines are anthelmintics for animals such as sheep, goats, cattle, horses, and Swine. 

A number of amidines have anthelmintic activity. Bunamidine (25), indicated for treatment of human pinworm infestations, is prepared from a-naphthylhexyl-ether (23) by Friedel-Crafts type reaction with cyanogen bromide and aluminum chloride to give nitrile (24). This, then, is reacted with the magnesium bromide salt of di-n-propylamine leading to the naph-thamidine structure (25). -... 

These include amitraz (110), prepared from 54, a member of the form amidine class, active against mites and ticks, that have replaced organophosphorus compounds. Notably, amitraz is active against newer strains of pyrethroid-resistant ticks. The reaction of diphenylamine (8) with sulfur in the presence of iodine as catalyst yields the anthelmintic (worming agent) phenothiazone (phenothiazine) (111) (Scheme 24). It is too toxic for human use, though it is an intermediate in the production of antipsychotic drugs. 

In addition to the compounds represented by formula 9,12 or 13, a number of non-cyclic amidines (14), dihydrothiazines and thiazolines (15-17) and 1-(2-aryIvinyl) pyridinium salts (18,19) have also been synthesized, many of which exhibit marked anthelmintic activity [8,11]. The SAR in many of these series was found to be in close concordance with the tetrahydropyrimidines. 

New anthelmintic agents which are already in use in veterinary medicine have been found in two cyclic amidine derivatives, pyrantel tartrate (Banminth, Strongid) (269) and morantel tartrate (Banminth II) (270). For references concerning their evaluation in sheep, cattle, pigs, horses, dogs, and man see Ref. 260. These compounds are most probably prepared by condensation of the appropriate thiophen aldehyde with 1,4,5,6-tetra-hydro-l,2-dimethylpyrimidine. Extensive investigations on structure-... 

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