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

Abstract

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 μM 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).

Further and new target-based benzimidazole anthelmintics active against Teladorsagia circumcincta

“…Type II compounds have been reported as potential inhibitors of 12-lipoxygenase [11] , and 5-lipoxygenase [ 12 ], as well as anti-Helicobacter pylori agents [ 13 ], anticancer [ 14 ], or as antiproliferative [ 15 ]. With respect to compounds types III and IV, descriptions on activities such as fungicidal [16][17][18][19][20] , antimalarial, anti-Trypanosoma brucei [ 21 ], anthelmintic [ 22 ], against HIV-1 proteases, or hepatitis B virus [ 23 ], neuroprotective agents targeting mGluR5 [ 24 ], inhibitors of interleukin-1-receptor-associated kinase-4 [25] antiproliferative [ 26 ], or inhibitors of 5-lipoxygenase [ 12 ] can be found.…”