Bis-cationic heteroaromatics as macrofilaricides: synthesis of bis-amidine and bis-guanylhydrazone derivatives of substituted imidazo[1,2-a]pyridines

A series of guanylhydrazone, amidine, and hydrazone derivatives of 2-phenylimidazo[1,2-a]pyridine have been prepared and evaluated for macrofilarial activity against Acanthocheilonema viteae and Brugia pahangi in jirds. Compounds with 4',6-bis-substitution by cyclic guanylhydrazone groups show activity. 4',6-Bis-amidines show some activity but are more toxic; 4'- or 6-monosubstituted compounds are inactive. 2,6-Bis-substituted compounds lacking the phenyl ring are inactive. 4',6-Bis-substituted compounds having additional double bonds inserted between the heterocyclic ring and the phenyl ring or between the substituent and the ring system show reduced activity.