{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:26:57Z","timestamp":1790202417508,"version":"4.1.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p>This study reports the synthesis of a series of calcium channel blockers via Biginelli\u2019s reaction. The core dihydropyridine (DHP) scaffold, an isostere of nifedipine, was synthesized using three aldehydes incorporated with trifluoromethyl (\u2013CF<jats:sub>3<\/jats:sub>) substitutions at the ortho, meta, and para positions. The resulting series <jats:bold>(4a\u2013c<\/jats:bold> to <jats:bold>9a\u2013c)<\/jats:bold> was evaluated for antihypertensive and calcium channel-blocking activities in male and female rats, administered intraperitoneally. Among the synthesized compounds, the ortho-substituted derivatives (<jats:bold>4a<\/jats:bold>, <jats:bold>7a<\/jats:bold>, <jats:bold>8a<\/jats:bold>, and <jats:bold>9a<\/jats:bold>) demonstrated the highest antihypertensive activity, exhibiting approximately 30% efficacy relative to nifedipine. These compounds also displayed IC<jats:sub>50<\/jats:sub> values comparable to nifedipine and were further assessed for binding affinity with 6M7H and 4MS2 through molecular docking studies. The final DHP derivatives were amides, synthesized through reactions with aniline, 4-methylaniline, and 4-nitroaniline. Notably, compound <jats:bold>9a<\/jats:bold> exhibited the highest docking score against both tested receptor proteins, highlighting its potential for further investigation.<\/jats:p>","DOI":"10.3389\/fchem.2025.1581037","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T05:40:21Z","timestamp":1747028421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of nifedipine isosteres: an integrated approach to the design, synthesis, and biological assessment of calcium channel blockers"],"prefix":"10.3389","volume":"13","author":[{"given":"Yasser M.","family":"Zohny","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir M.","family":"Awad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Alsaidan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha A.","family":"Rabie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.9734\/jpri\/2022\/v34i54a7235","article-title":"Role and complication of existing and newer calcium channel blockers in hypertension treatment","volume":"34","author":"Aljehani","year":"2022","journal-title":"J. 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