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ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 13 - 2025 | doi: 10.3389/fchem.2025.1581037
Development of Nifedipine Isosteres: An Integrated Approach 2 to Design, Synthesis, and Biological Assessment of Calcium 3 Channel Blockers 4
Provisionally accepted- 1Shaqra University, Shaqraa, Saudi Arabia
- 2Faculty of Pharmacy, Helwan University, Helwan, Cairo, Egypt
- 3College of Pharmacy, Al Jouf University, Sakaka, Saudi Arabia
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This study reports the synthesis of a series of calcium channel blockers via Biginelli's reaction. The 20 core dihydropyridine (DHP) scaffold, an isostere of Nifedipine, was synthesized using three alde-21 hydes substituted with -CF₃ at the ortho, meta, and para positions. The resulting series (4a-c to 9a-22 c) was evaluated for antihypertensive and calcium channel-blocking activity in male and female 23 rats, administered intraperitoneally. Among the synthesized compounds, the ortho-substituted de-24 rivatives (4a, 7a, 8a, and 9a) demonstrated the highest antihypertensive activity, exhibiting approx-25 imately 30% efficacy relative to Nifedipine. These compounds also displayed IC₅₀ values compara-26 ble to Nifedipine and were further assessed for binding affinity with 6M7H and 4MS2 through 27 molecular docking studies. The final DHP derivatives were amides, synthesized through reactions 28 with aniline, 4-methylaniline, and 4-nitroaniline. Notably, compound 9a exhibited the highest dock-29 ing score against both tested receptor proteins, highlighting its potential for further investigation.
Keywords: Nifedipine isosteres, Antihypertensive, Calcium channel blocking, SAR studies, docking 31 32
Received: 21 Feb 2025; Accepted: 14 Apr 2025.
Copyright: © 2025 Zohny, Awad, Alsaidam and Rabie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yasser Zohny, Shaqra University, Shaqraa, Saudi Arabia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.