SYNTHESIS RELATIONSHIP BETWEEN STRUCTURE AND ACTIVITY OF 2-NITROIMIDAZOLE DERIVATIVES

A number of 1,5-disubstituted 2-nitroimidazoles has been synthesized by diazotization and Gattermann reaction on the corresponding 2-aminoi midazoles prepared from amino acetals or amino lactones. Their antitrichomonal activity and acute oral toxicity in mice have been determined. Comparison with other series of nitroimidazoles shows that 1,5-dialkyl compounds are more active and less toxic in respect of monoalkyl or 1,4-dialkyl derivatives, whereas their activity is similar to that of 1,2-dialkyi-5-nitroimidazoles. The influence of steric effects and of partition coefficients is considered. The effect of functional substituents is also discussed. © 1969, American Chemical Society. All rights reserved.