A New Synthetic Method for Tetraazatricyclic Derivatives and Evaluation of Their Biological Properties

A new method for the synthesis of tetraazatricyclic compounds by a reaction of benzoyl isothiocyanates with 2-aminobenzimidazole is presented and a possible mechanism proposed. The new base-catalyzed degradation of the tetraazatricyclic ring has been carried out. A reaction of benzoyl isothiocyanate with 2-aminobenzoxazole, however, resulted in the formation of 3-benzoyl-1-(2-hydroxyphenyl)urea while a reaction with 2-aminobenzothiazole gave 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea. Density functional theory computed reaction mechanism for the formation of tetraazaatricyclic compounds is discussed. Biological screening of the compounds against Plasmodium falciparium and HIV-1 protease showed very little activity but they were moderately active against Trypanosoma brucei with an IC50 of 19.71 mu M for 11-(3-methoxyphenyl)-1,8,0,12-tetraazatricyclo [7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (4).