{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:12:56Z","timestamp":1790957576117,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research &amp; lnnovation, Ministry of Education in Saudi Arabia","award":["IFP2021-105"],"award-info":[{"award-number":["IFP2021-105"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pyrimidines play an important role in modern medical fields. They have a wide spectrum of biological activities such as antimicrobial, anticancer, anti-allergic, anti-leishmanial, antioxidant agents and others. Moreover, in recent years, 3,4-dihydropyrimidin-2(1H)ones have attracted researchers to synthesize them via Biginelli reaction and evaluate their antihypertensive activities as bioisosters of Nifedipine, which is a famous calcium channel blocker. Our new target compounds were prepared through one-pot reaction of thiourea 1, ethyl acetoacetate 2 and\/or 1H-indole-2-carbaldehyde, 2-chloroquinoline-3-carbaldehyde, 1,3-diphenyl-1H-pyrazole-4-carbaldehyde, 3a\u2013c in acid medium (HCl) yielding pyrimidines 4a\u2013c, which in turn were hydrolyzed to carboxylic acid derivatives 5a\u2013c which were chlorinated by SOCl2 to give acyl chlorides 6a\u2013c. Finally, the latter were reacted with some selected aromatic amines, namely, aniline, p-toluidine and p-nitroaniline, producing amides 7a\u2013c, 8a\u2013c, and 9a\u2013c. The purity of the prepared compounds was examined via TLC monitoring, and structures were confirmed by different spectroscopic techniques such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The in vivo evaluation of the antihypertensive activity revealed that compounds 4c, 7a, 7c, 8c, 9b and 9c had comparable antihypertensive properties with Nifedipine. On the other hand, the in vitro calcium channel blocking activity was evaluated by IC50 measurement and results revealed that compounds 4c, 7a, 7b, 7c, 8c, 9a, 9b, and 9c had comparable calcium channel blocking activity with the reference Nifedipine. Based on the aforementioned biological results, we selected compounds 8c and 9c to be docked onto Ryanodine and dihydropyridine receptors. Furthermore, we developed a structure\u2013activity relationship. The designed compounds in this study show promising activity profiles in reducing blood pressure and as calcium channel blockers, and could be considered as new potential antihypertensive and\/or antianginal agents.<\/jats:p>","DOI":"10.3390\/molecules28124869","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T02:01:33Z","timestamp":1687312893000},"page":"4869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Pyrimidine Derivatives as Potential Calcium Channel Blockers"],"prefix":"10.3390","volume":"28","author":[{"given":"Yasser M.","family":"Zohny","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Department, College of Pharmacy, Shaqra University, Dawadmi 11911, Saudi Arabia"},{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir M.","family":"Awad","sequence":"additional","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha A.","family":"Rabie","sequence":"additional","affiliation":[{"name":"Pharmacy Practice Department, College of Pharmacy, Shaqra University, Dawadmi 11911, Saudi Arabia"},{"name":"Pharmacology and Toxicology Department, School of Pharmacy, Cairo University, Cairo 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2848-2932","authenticated-orcid":false,"given":"Omar Awad","family":"Alsaidan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.hfc.2019.09.001","article-title":"Hypertension and heart failure: Prevention, targets, and treatment","volume":"16","author":"Barone","year":"2020","journal-title":"Heart Fail. 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