Synthesis and broncholytic activity of N-substituted 3-aminomethylthiazolo[3,2-a]-benzimidazole derivatives

Abstract

Previously we have described the synthesis of alkylaminomethyl derivatives of [3,2-a]benzimidazole [1,2]. It was found that these compounds possess antiulcerous [3], immunotropic [ 1,4], antiinflammatory and antiaggregation activity [2]. It was also established that some thiazolobenzimidazoles exhibit a rather pronounced broncholytic activity [5]. Therefore, it was of interest to synthesize new derivatives of this series and study their effect on the bronchial tonus of experimental animals.The new compounds were synthesized proceeding from the previously described 3-chloromethylthiazolo[3,2-a]benzimidazole (I) [ 1], from which intermediate bases were obtained using the reactions of nucleophilic substitution with alkylamines, morpholine, piperidine, and thiourea. The resulting bases (II) form stable salts with mineral acids and methyl iodide.The structures of the synthesized compounds were confirmed by the data of IR spectrophotometry and IH NMR spectroscopy. The IR spectra of compounds III-VIII (Table 1) contain the absorption bands attributed to the bonds C=C and C=N in the cycles and -NH, -OH, and -NH+CI -groups. The IH NMR spectra of compounds III-V exhibit characteristic singlets from methylene protons (3-CH2), multiplets of aromatic protons, and some other signals (Table I). EXPERIMENTAL CHEMICAL PARTThe IH NMR spectra were measured on a Tesla-567 spectrometer (Czech Republic) using trifluoroacetic acid or DMSO-d6 as solvents and HMDS or TMS as internal standards. The IR spectra were recorded on an UR-20 spectrophotometer (Germany) using samples prepared as nujol mulls. The course of the reactions was monitored and the pu-