Synthesis and pharmacological activity of salts of 4-(2-dialkylaminoethyl)-pyrrolo [1,2-a]benzimidazoles

Abstract

In recent years, increasing attention of researchers has been drawn to polycyclic systems involving nitrogen-bridged pyrrole, indole, imidazole, and benzimidazole nuclei. Both natural and synthetic derivatives of these compounds are now widely used in medical practice [1 -3 ] . One representative of this class is a 4H-pyrrolo[i,2-a]benzimidazolearomatic x-redundant system originally synthesized in 1966 [4, 5]. Pyyroio[l,2-a]benzimidazole exhibits a n-donor ability, being markedly superior in this respect to other strong electron donors such as phenothiazine and pyrimidine [6, 7]. Taking into account the role of donor-acceptor interactions in some biological processes and the relationship between physiological activity of substances with their electron-donor ability [8, 9], we may anticipate that the search for biologically active compounds in this system will give promising results. However, despite quite extensive investigations into the chemistry of pyrrolo[ 1,2-a]benzimidazole [ 10], the pharmacological properties of derivatives of this system have not yet beenstudied (unlike the derivatives of 2,3-dihydropyrroio[l, 2-a]benzimidazole [1 !, 12]). In order to fill the gap [4, 10], we have synthesized new derivatives of pyyrolo[i,2-a]benzimidazole (IV) containing dialkylaminoethyl pharmacophore groups in position 4 of the pyrrole ring. The reaction of 2-alkyl(aralkyl)-l-dialkylaminoethylbenzimidazoles (II) (obtained by alkylation of benzimidazoles (1) with diaikylaminoethylchlorides in acetone in the presence of excess alkali, cf. [13, 14]) with a-bromoacetophenones proceeds only at the nitrogen atom N 3 of the imidazole ring to form quaternary salts (IIl) with high yield. In the case of bromopinacoline, the best result was obtained when the reaction was performed in the absence of solvent.