Search for fungistatics in the imidazole series

Abstract

New imidazole derivatives with fungistatic activity were synthesized at the NCRSRVI branch of FSBSC Federal Rostov Agrarian Scientific Center. The initial compound 4,5-dichlorimidazole was obtained according to the method described in the literature [3]. Structures 1, 4, 6, 7, 8 - 11, 14 - 17, 19, 20, 22, 24 they were synthesized by alkylation of 4,5-dichlorimidazole with corresponding halide alkyls in an alkaline medium. Alcohol 5 was obtained by reducing ketone with sodium borohydride in ethanol. Bigeterocycles 10, 13 were obtained by the reaction of 4,5-dichlorimidazole with corresponding chloronitropyridines by boiling in dimethylformamide in the presence of potassium carbonate. Compound 10 was obtained under similar conditions, but ortho-chloronitrobenzene was used as an aryl derivative. The preparation 23 was obtained by acylation using a chlorocarbon ester of the corresponding N-(4-aminophenylmethyl) 4,5-dichlorimidazole, which, in turn, was synthesized from a nitro derivative by reduction with iron in ethanol in the presence of a catalytic amount of hydrochloric acid. Preparation 18 is obtained from the methyl ester of 4,5-dichlorimidazole and acetic acid and hydrazine in an alcoholic medium. The study of fungistatic activity showed that the size of the culture growth retardation zone crucially depends on the type of substituents in the nitrogen atom of the imidazole cycle. First of all, this applies to the lipophilicity of the substituent: the higher the lipophilicity (of the compound 1, 4, 6, 7, 20, 22-24), the higher the activity of the connection. However, lipophilicity obviously should not exceed certain limits: the most lipophilic compounds 2 and 3 are significantly inferior in activity to slightly less lipophilic compounds 1, 4, 6, 7, 20, 22-24. Polar substituents of the nitrogen atom (compounds 5, 8, 11, 16-18, 23) completely suppress fungistatic activity. The aryl substituent of the nitrogen atom of the imidazole ring (compound 10), as well as the nitrogetaryl substituents (compounds 12 and 13) have significant fungistatic activity.