Synthesis and prediction of the biological activity of heterocyclic n-derivatives naphthoquinone

: 69-75
Lviv Polytechnic National University
Lviv Polytechnic National University
Lviv Polytechnic National University
Lviv Polytechnic National University
Institute of Organic Chemistry, NAS of Ukrainе

The most urgent task of organic and pharmaceutical chemistry today is the search for new biologically active compounds, which in future can be used as promising substances for the development of new low-toxic, high-performance medicinal products. To this end, heterocyclic N-derivatives of 1,4-dichloroanotoquinone were synthesized and their drug-like characteristics were determined.

 On the basis of the literature data, we carried out the synthesis of aminopyrazole derivatives of dichloro-petroquinone. To obtain new aminopyrazole derivatives of dichloro-petroquinone, a nucleophilic substitution of a chlorine atom in a 2,3-dichloro-1,4-naphthoquinone by a pyrazole fragment was carried out (interaction of the equimolar amount of the corresponding aminopyrazole derivative with 2,3-dichloro-1,4-naphthoquinone in alcohol and with carbonate sodium as an acceptor of HCl). The following heterocyclic derivatives of dichlorofluoroquinone were obtained: 2-chloro-3 - ((1-methyl-1H-pyrazol-4-yl) amino) naphthalene-1,4-dione, 2-chloro-3 - ((1-methyl-1H 2-chloro-3 - ((3- (p-tolyl) -1H-pyrazol-5-yl) amino) naphthalene-1,4-dione and ethyl 4 - ((3-chloro-1,4-dioxo-1,4-dihydro-naphthalen-2-yl) amino) -1-phenyl-1H-pyrazole-3-carboxylate.

For synthesized substances, computer biological screening was carried out under the PASS program and calculated criteria of the appearance of the liver. The results of the predicted biological activity of aminopyrazoles with the quinone fragment showed that the synthesized compounds have pronounced antitumor activity, analgesic, antiparkinsonian, anti-neurodegenerative activity, activity against diabetic neuropathy, as well as the possibility of their use as inhibitors of many enzymes. Analyzing the obtained results of calculating the criteria for the appearance of the liver, it can be argued that heterocyclic naphthoquinone derivatives do not have any deviations from the Lipinsky's rules. And, consequently, it is advisable to carry out further experimental biological studies of synthesized compounds.

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