A series of quaternary 2-phenylimidazo[1,2-a]pyridinum salts has been prepared and evaluated for antiparasitic activity. Primary attention was focused on derivatives with amido, substituted hydrazone, and heterocyclic functionality at the para position of the phenyl substituent. Guanylhydrazones and N-substituted guanylhydrazones of the 4'-formyl-substituted compounds are very active against the blood state Trypanosoma rhodesiense in mice by subcutaneous or oral administration. The most potent compounds attain 100% survival for 30 days at doses of less than 1.0 mg/kg (sc) and greater than 5.0 mg/kg (po). Weaker activity is noted for certain other 4'-substituents such as carboxamidines and carboxamide oximes. Considerable variation in structure, including replacing of the imidazo [1,2-a]pyridinium ring by other cationic heterocyclic rings and insertion of linking groups between the heterocyclic ring and phenyl group, can be done, and a high level of activity is maintained. Relationships between these structural changes and biological activity are discussed.

A series of substituted 2‐aryl imidazo[1,2‐a]pyridines has been prepared in which a variety of substituents are introduced on the 4′‐position of the phenyl ring and on the 3, 5, 6 or 7 position of the heterocyclic ring. Most examples have acetamido, bromo, cyano, or formyl substituents at the 4′‐position. Analogous imidazo‐[2,1‐b]fhiazoles and imidazo[1,2‐a]pyrimidines have also been prepared. Another series of compounds consisting of 4′‐formylphenoxymethyl derivatives of imidazole, the three positional isomers of pyridine, thiazole, benzimidazole and ring‐substituted imidazo[1,2‐a]pyridines has been prepared. 2‐(4′‐Formylphenylethenyl) derivatives of imidazole and imidazo[1,2‐a]pyridine were also prepared.

The 2‐arylimidazopyridines (III) are obtained by cyclocondensation of the 2‐aminopyridines (I) with the substituted α‐bromoacetophenones (II).