Electronic structure-activity relationship for derivatives of propenone. Communication II. 2-cinnamoylbenzimidazoles and 2-(β-benzoylvinyl)-1-methylbenzimidazoles

Abstract

Our systematic investigations of some regularities of the electronic structure-activity relationship (ESAR) in a series of chalcone derivatives and the corresponding heterocyclic analogs substantiated the structural characteristics that determine the antioxidant, antiallergic, antiinflammatory, and other types of activity [1, 2]. In earlier communications we described the results of antiallergic activity studies [1] and the analysis of ESAR for derivatives of 4-carboxyvinylenechalcones and 3-einnamoylcoumarins [3]. As a continuation of these studies, we considered it reasonable to obtain heterocyclic analogs of chalcone, in which one of the aromatic rings was replaced by the benzimidazole fragment. Benzimidazole derivatives are known to process more than 25 types of pharmacological action, including antiallergic [4] and immunomodulating activity (dibazole). We synthesized two types of benzimidazole analogs, 2cinnamoylbenzimidazoles and 2-(13-benzoylvinyl)-l-methylbenzimidazoles (see Table I). Compounds I a n were synthesized by condensation of 2-acetylbenzimidazole with aromatic aldehydes in the presence of a basic or acidic catalyst; compounds I I a n were synthesized by the reaction of 2-formyl-l-methylbenzimidazole with corresponding acetophenones. Biological testing of the compounds obtained revealed pronounced antiallergic and sedative activities (AA and SA, respectively) as well as moderate hypotensive and antihemorrhagic activities. The outlined conclusions [3] about the decisive contribution of electronic parameters of the ct,IB-unsaturated carbonyl fragment to the biological activity of chalcone and coumarin derivatives served as a basis for the search for ESAR in a series of synthesized benzimidazole analogs of chalcone.