Structure-activity relationship of 2-aminodibenzothiophene pharmacophore and the discovery of aminobenzothiophenes as potent inhibitors of Mycobacterium smegmatis.

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide and its current treatments have been complicated with the emergence of multi-drug resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains. Therefore, the discovery of new antitubercular agents is in need to overcome this problem. In our efforts to discover novel candidates for the treatment of tuberculosis, we describe in this work in vitro activityagainstM. smegmatis for a series of aminated benzo-fused heterocycles, particularly, dibenzothiophene to explore the structure-activity relationship of 2-aminodibenzothiophene 3aa. From these studies, three compounds 5-aminobenzothiophene 3ia, 6-aminobenzothiophene 3ma (MIC: 0.78 µg/mL) and 5-aminobenzofuran 3ja (MIC: 1.56 µg/mL) were identified as potent inhibitors of M. smegmatis with low cytotoxicity. These results suggested the significance of these compounds 3ia, 3ja and 3ma for the future development of candidate agents to treat tuberculosis.

One-Pot Synthesis of Aminated Benzo-Fused Heterocycles and N-Substituted Dibenzothiophenes via Copper-Catalyzed Ullmann Type Reaction.

We report here a direct and effective method to synthesize a primary amine of several polycyclic aromatic compounds. This reaction has been achieved through copper (I)-catalyzed Ullmann C-N coupling. Furthermore, this strategy allows the synthesis of new N-substituted dibenzothiophene derivatives through the coupling of 2-bromodibenzothiophene with various ranges of primary and secondary amines. The use of inexpensive catalysts, aqueous ammonia as the convenient source of ammonia and ligand free, makes this protocol environmentally and economically favorable for the synthesis of these compounds.