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A New Synthetic Method for Tetraazatricyclic Derivatives and Evaluation of Their Biological Properties
Author(s) -
Odame Felix,
Betz Richard,
Hosten Eric C.,
Krause Jason,
Isaacs Michelle,
Hoppe Heinrich C.,
Khanye Setshaba D.,
Sayed Yasien,
Frost Prof Carminita,
Lobb Kevin A.,
Tshentu Zenixole R.
Publication year - 2018
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201802930
Subject(s) - thiourea , chemistry , isothiocyanate , combinatorial chemistry , urea , medicinal chemistry , organic chemistry
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 IC 50 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).