Published June 30, 2024 | Version Version 00

Dataset for Computer-aided rational design and synthesis of new potential antihypertensive agents among 1,2,3-triazole-containing nifedipine analogs

  • 1. ROR icon V. N. Karazin Kharkiv National University
  • 1. ROR icon V. N. Karazin Kharkiv National University
  • 2. National University of Pharmacy
  • 3. ROR icon University of Chemistry and Technology, Prague
  • 4. National University of Pharmacy: Kharkov, UA
  • 5. Life Chemicals Inc.

Description

1,2,3-Triazole-containing Nifedipine analogues offer the opportunity to increase biostability, bioavailability, efficacy and binding selectivity to target receptors. Here, we applied a computer-aided rational design for identifying new Nifedipine analogues containing a 1,2,3-triazole moiety. First, a new chemical library of 796 derivatives combining the DHP fragment and 1,2,3-triazole moiety was generated. Second, to reduce the library size, the library was pre-filtered using two 3D-pharmacophore models with different complexity, which allowed us to gradually reduce the chemical space, ending up with 26 hit candidates. Molecular docking calculations against the rCav1.1 receptor allowed the identification of eight derivatives 5a-h, characterized by the binding affinity towards the rCav1.1 receptor of the same level as approved Nifedipine-like drugs. Next, our molecular docking results were used to guide and optimize the retrosynthetic approaches for new analogues of Nifedipine as promising antihypertensive agents. So, a retrosynthetic approach for Nifedipine analogues with a 1,2,3-triazole ring in position 4 was proposed. Finally, eight analogues 5a-h determined by molecular docking calculations were synthesized using the suggested retrosynthetic approach.

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Additional details

Related works

Is supplement to
Journal article: 10.15587/2519-4852.2024.291626 (DOI)

Funding

European Union
MSCA4Ukraine project 1232655
The State Institution «Public Health Center of the Ministry of Health of Ukraine»
Hybrid pharmacophore approach to innovative pharmacologically active compounds of hypotensive action - molecular design, synthesis and screening of the hybrid molecules containing 1,4-dihydropyridine and 1,2,3-triazole frameworks 0123U101752

Dates

Accepted
2024-06-30

References

  • Kyrychenko, A., Bylov, I., Geleverya, A., Kovalenko, S., Zhuravel, I., Fetyukhin, V., & Langer, T. (2024). Computer-aided rational design and synthesis of new potential antihypertensive agents among 1,2,3-triazole-containing nifedipine analogs. ScienceRise: Pharmaceutical Science, (3 (49), 4–12. https://doi.org/10.15587/2519-4852.2024.291626