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Using novel click chemistry algorithm to design D3R inhibitors as blood–brain barrier permeants
Future Medicinal Chemistry. 2023. Vol. 15. No. 11. P. 923–935.
Dopamine receptor D3 (D3R) has gained attention as a promising therapeutic target for neurological disorders. In this study, an innovative in silico click reaction strategy was employed to identify potential D3R binders. The ligand template, 1-phenyl-4-[4-(1H-1,2,3-triazol-5-yl)butyl]piperazine, with substitution at the 1,2,3-triazole ring, served as the starting point. Generated compounds underwent filtration based on their brain-to-blood concentration ratio (logBB), leading to the identification of 1-{4-[1-(decahydronaphthalen-1-yl)-1H-1,2,3-triazol-5-yl]butyl}-4-phenylpiperazine as the most promising candidate, displaying superior D3R affinity and blood-brain barrier (BBB) permeability compared to the reference ligand, eticlopride. Molecular dynamics simulations further supported these findings. This study presents a novel hit for designing D3R ligands and establishes a workflow utilizing in silico click chemistry to screen compounds with BBB permeability. The proposed click reaction-based algorithm holds significant potential as a valuable tool in the development of effective antipsychotic compounds.
Publication based on the results of:
Nazarov Alexey A., Dudarova N., Zhidkova O. et al., Journal of Photochemistry and Photobiology A: Chemistry 2026 Vol. 483 Article 117654
Сyclocondensation of phenyl, ortho-bromophenyl, para-phenylphenyl, para-methoxycarbonylphenyl, para-tolyl and para-methoxyphenyl boronic acid with curcumin in the presence of K3PO4 upon refluxing in 1,4-dioxane for 24 h leads to the formation of curcumin-based 2,2-diaryl-1,3,2-dioxaborines in good yields. The absorption-emission spectra of the synthesized fluorescent conjugates and 1,3,2-dioxaborine with para-biphenyl boronic substituent demonstrated the highest quantum yield. Among the compounds studied, conjugate curcumin with para-methoxycarbonylphenyl boronic substituent ...
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Chemical Papers 2026
Benzenoid hydrocarbons are structurally regular aromatic compounds, which makes them well suited for quantitative structure–property relationship (QSPR) studies. This study presents a QSPR analysis of nineteen benzenoid hydrocarbon species using degree-based topological co-indices. We developed a Python program to compute eleven degree-based topological co-indices from molecular graphs and evaluated their ability to explain variations in ...
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Gurina D., Fashchevsky K. A., Oparin R. D. et al., Surfaces and Interfaces 2026 Vol. 98 Article 110545
In this work, we combine experimental characterization and molecular dynamics (MD) simulations to elucidate the molecular mechanisms governing the impregnation of mefenamic acid (MFA) into nanocrystalline cellulose (NCC) aerogels. NCC aerogels were impregnated with MFA in scCO2, and low-temperature nitrogen adsorption revealed a concentration-dependent decrease in surface area, pore volume, and pore size, with an ...
Added: September 8, 2026
Proskurnina E., Liaukovich K., Bychkovskaya L. et al., Metabolites 2023 Vol. 13 No. 1 P. 73
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Budkov Y., Journal of Chemical Physics 2026 Vol. 165 No. 9 Article 094902
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Added: September 2, 2026
Novikov A., Polyhedron 2026 Vol. 299 Article 118358
Two new supramolecular halometalate hybrid complexes, (H2bpen){[MCl5](I2)} (M = Sb(III) (1) and Bi(III) (2); bpen – 1,2-Bis(4-pyridyl)ethylene, have been prepared. Despite very close similarity of the nature of cations, they reveal significant structural difference from the (H2bpe){[MCl5](I2)} (bpe – 1,2-bis(4-pyridil)ethane) reported earlier. We discuss these features, along with thermal stability, optical properties as well as Raman spectra ...
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Belousov Y., Кискин М. А., Sidoruk A. et al., Australian Journal of Chemistry 2022 Vol. 75 No. 9 P. 572–580
Four new complexes [Ln(pfaa)3(H2O)2]n (Ln = Eu (1), Tb (2)) and [Ln2Cd2(pfaa)10 (phen)2(EtOH)2]·2MeCN (Ln = Eu (3), Tb (4), phen = 1,10-phenanthroline) based on pentaphorphenylacetic acid (Hpfaa) have been prepared and completely investigated. The structures of compounds 1 and 3 were studied by single crystal X-ray diffraction analysis: the isostructural complexes 1 and 2 represent ...
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Mazur D., Petr E. Brandyshev, Doronin S. et al., Electrochimica Acta 2026 Vol. 577 Article 149729
The electric double layer (EDL) at a single-crystal metal surface is controlled not only by the electrolyte composition and the electrode potential, but also by the atomic structure of the surface itself. This makes the Ag(hkl)/NaF interface a stringent test for continuum theories of the EDL. In the third part of our series, we examine ...
Added: August 20, 2026
Budkov Y., Kalikin N., Journal of Chemical Physics 2026 Vol. 165 Article 064506
A self-consistent statistical-mechanical theory of the Hall effect in electrolyte solutions is developed by extending the self-consistent Debye–Hückel–Onsager (SCDHO) framework to crossed electric and magnetic fields. The theory incorporates non-local ionic charge distributions via Slater-type form factors, regularizing the Coulomb interaction at short range, and accounts for dielectric friction through ion-specific coefficients, employing experimental values ...
Added: August 12, 2026
Obijiofor O., Alexander S. Novikov, New Journal of Chemistry 2026 Vol. 50 No. 33 P. 13931–13957
The rational design of coinage metal nanocarriers requires a mechanistic understanding of metal-drug binding and predictive descriptors that translate molecular interactions into design rules. Using DFT (B3LYP-D3BJ/def2-TZVP, SMD water), we systematically investigated the binding of 5-fluorouracil (5-FU) and levodopa (l-DOPA) to neutral and cationic homo- and heteronuclear dimers of Au, Ag, and Cu (Au2, Ag2, ...
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Elena A. Andresyuk, Natalya O. Porozova, Londaridze G. et al., Frontiers in Oncology 2026 Vol. 16 Article 1875861
Inhibition of the PD-1/PD-L1 axis has become a clinical standard across multiple malignancies, yet durable benefit remains restricted to selected settings, and many biologically rational combinations fail to maintain clinical benefit in late-phase evaluation. This structured, registry-derived narrative review, supported by expert-guided interpretation, was designed to identify the most clinically meaningful development directions among strategies ...
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Voropaeva D., S. Novikova, I. Stenina et al., Solid State Ionics 2026 Vol. 445 Article 117288
Composite gel polymer electrolytes based on a perfluorinated sulfonic acid cation-exchange MF-4SC membrane
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sCeO2, and sTiO2, respectively) were prepared by casting from a dispersion in N,N-dimethylformamide and
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Korogod D., Shapeev A., Ivan S. Novikov, Physical Review B: Condensed Matter and Materials Physics 2026 Vol. 114 No. 2 Article 024104
We present two models with explicit long-range electrostatics in the form of Coulomb interactions. Both models include point charges depending on their local atomic environments, and the second model also conserves a total charge of an atomic system. We combine the proposed long-range models with the local moment tensor potential (MTP) and demonstrate that they ...
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Sun Z., Khvostikov A., Krylov A. et al., Machine Learning and Knowledge Extraction 2026 Vol. 8 No. 1 Article 8
Whole-slide histology images (WSIs) can exceed 100 k × 100 k pixels, making direct pixel-level segmentation infeasible and requiring patch-level classification as a practical alternative for downstream WSI segmentation. However, most approaches either treat patches independently, ignoring spatial and biological context, or rely on deep graph models prone to oversmoothing and loss of local tissue ...
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Vamotinib (PF-114) is a 3rd -generation, ATP-competitive oral tyrosine kinase inhibitor (TKI) active against wild-type and mutated BCR::ABL1 isoforms including BCR::ABL1T315I. We present final results of a phase-1 vamotinib dose-escalation study to identify maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) followed by expansion cohorts. 51 subjects with chronic myeloid leukaemia (CML) failing ≥ 1 2nd generation TKI or with BCR::ABL1T315I were ...
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Petrovskaya A., Tverskoi A., Medvedeva A. et al., Communications Biology 2023 No. 6 Article 416
Alzheimer’s disease (AD) is a complex neurodegenerative disease with no existing treatment leading to full recovery. The blood-brain barrier (BBB) breakdown usually precedes the advent of first symptoms in AD and accompanies the progression of the disease. At the same time deliberate BBB opening may be beneficial for drug delivery in AD. Non-invasive brain stimulation ...
Added: December 1, 2023
Grin I., Mechetin G., Kasymov R. et al., Molecules 2021 Vol. 26 No. 21 Article 6668
Uracil–DNA glycosylases are enzymes that excise uracil bases appearing in DNA as a result of cytosine deamination or accidental dUMP incorporation from the dUTP pool. The activity of Family 1 uracil–DNA glycosylase (UNG) activity limits the efficiency of antimetabolite drugs and is essential for virulence in some bacterial and viral infections. Thus, UNG is regarded ...
Added: November 24, 2021
Stroganov O., Novikov, FN, Medvedev, MG et al., Journal of Computer-Aided Molecular Design 2020 Vol. 34 No. 2 P. 121–130
The rapid development of new machine learning techniques led to significant progress in the area of computer-aided drug design. However, despite the enormous predictive power of new methods, they lack explainability and are often used as black boxes. The most important decisions in drug discovery are still made by human experts who rely on intuitions ...
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Vladimir A. Korshun, Bioconjugate Chemistry 2017 Vol. 28 No. 10 P. 2599–2607
We developed a novel technique for the efficient conjugation of oligonucleotides with various alkyl azides such as
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Иваненков Я., Жаворонков А., Ямиданов Р. et al., Frontiers in Pharmacology 2019 Vol. 10 No. 913 P. 1–15
Many pharmaceutical companies are avoiding the development of novel antibacterials due to a range of rational reasons and the high risk of failure. However, there is an urgent need for novel antibiotics especially against resistant bacterial strains. Available in silico models suffer from many drawbacks and, therefore, are not applicable for scoring novel molecules with high structural ...
Added: October 1, 2019
Nikishina Y. O., Murtazina A. R., Sapronova A. Y. et al., Russian Journal of Developmental Biology 2016 Vol. 47 No. 5 P. 260–268
The goal of the present study was to verify our hypothesis of humoral interaction between the norepinephrine secreting organs in the perinatal period of ontogenesis that is aimed at the sustaining of physiologically active concentration of norepinephrine in blood. The objects of the study were the transitory organs, such as brain, organ of Zuckerkandl, and ...
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