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Molecular Docking, PASS Prediction, Pharmacokinetic and Toxicity Studies of Focal Adhesion Kinase Inhibitors
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Modeling of New VHR Inhibitors Based on 4H-1,3,5-Oxadiazine Derivatives †

Department of Pharmacy and Technology of Organic Substances, Ukrainian State University of Chemical Technology, Gagarin Ave 8, 49005 Dnipro, Ukraine
Author to whom correspondence should be addressed.
Presented at the 8th International Electronic Conference on Medicinal Chemistry, 1–30 November 2022; Available online:
Med. Sci. Forum 2022, 14(1), 64;
Published: 1 November 2022
(This article belongs to the Proceedings of The 8th International Electronic Conference on Medicinal Chemistry)


Vaccinia H1-related phosphatase (VHR) is a dual-specific phosphatase that is a promising potential target for the treatment of many human diseases. In this work, we have proposed a series of 6-(4-chlorophenyl)-N-aryl-4-(trichloromethyl)-4H-1,3,5-oxadiazin-2-amines as potential VHR inhibitors. The SuperPred online server predicts VHR inhibition for the studied compounds with a probability of 88.88–98.51%. To establish the efficiency of binding of 4H-1,3,5-oxadiazine derivatives to the active site of VHR (PDB ID: 3F81) in the AutoDock Vina program, we have carried out molecular docking studies. According to the results, the studied compounds effectively interact with the hydrophobic region of the VHR active site due to aromatic rings and the trichloromethyl group, but the polar catalytic cavity is not involved, and therefore inhibition cannot be effective. In this regard, we have built a number of model compounds containing a sulfate group and its derivatives (methyl ester and amide) in the para-position of the arylamine fragment. According to the results of molecular docking, these compounds effectively bind to the polar catalytic cavity of the enzyme due to hydrogen bonds, but due to the relative rigidity of their molecules, hydrophobic interactions are not fully realized. Therefore, in these model compounds between the arylamine fragment and the sulfo group, we introduced a spacer with a length of one to three methylene groups. Hit compounds have been selected—2-(4-((6-(4-chlorophenyl)-4-(trichloromethyl)-4H-1,3,5-oxadiazin-2-yl)amino)phenyl)ethane-1-sulfonic acid and its amide.

Supplementary Materials

The following supporting information can be downloaded at:, Conference poster.

Author Contributions

E.R.L.; methodology, formal analysis, investigation. O.O.H.; methodology, formal analysis. P.V.Z.; conceptualization, methodology, writing—original draft, formal analysis, investigation, visualization, project administration. V.V.K.; validation, resources, writing—review and editing. A.V.K.; validation, supervision, writing—review and editing. All authors have read and agreed to the published version of the manuscript.


This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.
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MDPI and ACS Style

Lominoga, E.R.; Zadorozhnii, P.V.; Hrek, O.O.; Kiselev, V.V.; Kharchenko, A.V. Modeling of New VHR Inhibitors Based on 4H-1,3,5-Oxadiazine Derivatives. Med. Sci. Forum 2022, 14, 64.

AMA Style

Lominoga ER, Zadorozhnii PV, Hrek OO, Kiselev VV, Kharchenko AV. Modeling of New VHR Inhibitors Based on 4H-1,3,5-Oxadiazine Derivatives. Medical Sciences Forum. 2022; 14(1):64.

Chicago/Turabian Style

Lominoga, Elizaveta R., Pavlo V. Zadorozhnii, Olha O. Hrek, Vadym V. Kiselev, and Aleksandr V. Kharchenko. 2022. "Modeling of New VHR Inhibitors Based on 4H-1,3,5-Oxadiazine Derivatives" Medical Sciences Forum 14, no. 1: 64.

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