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IN SILICO ANALYSIS OF 6-(4-CHLOROPHENYL)-N-ARYL-4- (TRICHLOROMETHYL)-4H-1,3,5-OXADIAZIN-2-AMINES AS POTENTIAL ANTAGONISTS OF VEGFR-1

Pavlo V. Zadorozhnii, Ihor O. Pokotylo, Vadym V. Kiselev, Aleksandr V. Kharchenko, Oxana V. Okhtina

In this study, the antagonistic activity of 6-(4-chlorophenyl)-N-aryl-4-(trichloromethyl)-4H-1,3,5-oxadiazin-2-amines against the vascular endothelial growth factor receptor (VEGFR-1) was analyzed using the PASS system. It was shown that the probability of antagonism of the analyzed compounds towards VEGFR-1 formed 24.7-59.9%. N,6-bis(4-chlorophenyl)-4-(trichloromethyl)-4H-1,3,5-oxadiazin-2-amine showed the best results, for which Pa was almost 60%. It was established that the introduction of ether and ester groups into the aromatic substituent of the studied compound significantly reduced the probability of antagonism towards VEGFR-1. It was shown that the introduction of any substituent in the para- position of the aromatic ring increased the probability of manifestation of this type of biological activity compared with ortho- and meta- isomers. For the studied 4H-1,3,5-oxadiazine derivatives, acute toxicity for rats was calculated by the intravenous and oral routes of administration. All compounds were tested for compliance with Lipinski criteria. Keywords: In silico, PASS, VEGF, VEGFR-1, 1,3,5-oxadiazine, GUSAR

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