Synthesis of new derivatives of indenoquinoxalinecarboxylic acids with amines and in silico prediction of their biological activity

The corresponding amide derivatives of 11-oxoindeno[1,2-b]quinoxaline-6-carboxylic acid were synthesized in good yields by interaction with amines (N,N-dimethylpropane-1,3-diamine, novocaine, 2,6-dimethylpyrimidin-4-amine). The technique is simple and well reproducible. It provides preliminary activation of the carboxyl group by ethyl ester of monochlorocarbonic acid with its conversion to anhydride in chloroform in the presence of triethylamine. Anhydride gently reacts with amines under the same conditions without preliminary isolation to form the corresponding derivatives. Physicochemical and pharmacokinetic properties of the synthesized compounds were predicted using the ADMETlab 3.0 program. All tested compounds corresponded to Lipinsky's rule and can be classified as "drug-like". Pharmacokinetic parameters (clearance, half-life, ability to penetrate the blood-brain barrier and be absorbed in the intestine) indicated the possibility of their oral use. Computer screening using the PharmMapper database confirmed the ability of the synthesized compounds to bind to a number of biological targets involved in cell replication and division. This indicates their potential for intercalation into DNA for the treatment of viral infections and tumors and the prospects for their further studies using in vitro methods.