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Synthesis, Molecular Docking Study, and Molecular Dynamics Simulation of New 1,3-Dimethyl-5-methylidenebarbituric Acid Derivatives Prepared by Cyclobutane Cleavage

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Abstract

Various organic derivatives of 1,3-dimethylbarbituric acid attract widespread interest as biologically active compounds, medicinal agents, and precursors in organic synthesis. The chemical reactivity of the cyclobutane moiety in 1,3-dimethyl-5-methylidenebarbituric acid dimer (2) was examined at room temperature toward various primary aliphatic amines (benzylamine, 4-methoxybenzylamine, and 3-fluorobenzylamine) and hydroxide ion, as well as in acidic medium. New compounds were prepared by ring-opening of the cyclobutane moiety via nucleophile attack on the exocyclic methylene group. The structures of the synthesized compounds were elucidated by employing 1H and 13C NMR (including DEPT) and mass spectrometric techniques. Molecular docking revealed a high binding affinity (–9.0 kcal/mol) of one of the obtained compounds (6). In addition, the molecular dynamics simulation and binding free energy calculation data confirmed that compound 6 is the most stable among the others.

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Funding

The authors gratefully acknowledge the financial support from the Deanship of Scientific Research, University of Jordan.

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Authors and Affiliations

  1. Department of Chemistry, Ulla Science and Arts College, Taibah University, 41477, Madinah Manorah, Saudi Arabia

    M. Al-Ghorbani

  2. Department of Chemistry, College of Education, University of Thamar, 87246, Dhamar, Yemen

    M. Al-Ghorbani

  3. Department of Chemistry, The University of Jordan, 11972, Amman, Jordan

    K. Sweidan, H. A. Krefeh & M. AlDamen

  4. Department of Chemical Science and Engineering, School of Engineering, Kathmandu University, 45200, Dhulikhel, Nepal

    R. Joshi

  5. Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education & Research, 570015, Mysore, Karnataka, India

    R. Ramu

Authors
  1. M. Al-Ghorbani
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  2. K. Sweidan
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  3. H. A. Krefeh
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  4. R. Joshi
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  5. R. Ramu
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  6. M. AlDamen
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Correspondence to M. Al-Ghorbani or K. Sweidan.

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Al-Ghorbani, M., Sweidan, K., Krefeh, H.A. et al. Synthesis, Molecular Docking Study, and Molecular Dynamics Simulation of New 1,3-Dimethyl-5-methylidenebarbituric Acid Derivatives Prepared by Cyclobutane Cleavage. Russ J Org Chem 59, 445–454 (2023). https://doi.org/10.1134/S1070428023030120

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