{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:24:39Z","timestamp":1792441479714,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2022R86"],"award-info":[{"award-number":["PNURSP2022R86"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Some new pyrimidine derivatives comprising arylsulfonylhydrazino, ethoxycarbonylhydrazino, thiocarbamoylhydrazino and substituted hydrazone and thiosemicarbazide functionalities were prepared from Biginelli-derived pyrimidine precursors. Heterocyclic ring systems such as pyrazole, pyrazolidinedione, thiazoline and thiazolidinone ring systems were also incorporated into the designed pyrimidine core. Furthermore, fused triazolopyrimidine and pyrimidotriazine ring systems were prepared. The synthesized compounds were evaluated for their calcium channel blocking activity as potential hypotensive agents. Compounds 2, 3a, 3b, 4, 11 and 13 showed the highest ex vivo calcium channel blocking activities compared with the reference drug nifedipine. Compounds 2 and 11 were selected for further biological evaluation. They revealed good hypotensive activities following intravenous administration in dogs. Furthermore, 2 and 11 displayed drug-like in silico ADME parameters. A ligand-based pharmacophore model was developed to provide adequate information about the binding mode of the newly synthesized active compounds 2, 3a, 3b, 4, 11 and 13. This may also serve as a reliable basis for designing new active pyrimidine-based calcium channel blockers.<\/jats:p>","DOI":"10.3390\/molecules27072240","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:28:39Z","timestamp":1648675719000},"page":"2240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Design, Synthesis, Pharmacodynamic and In Silico Pharmacokinetic Evaluation of Some Novel Biginelli-Derived Pyrimidines and Fused Pyrimidines as Calcium Channel Blockers"],"prefix":"10.3390","volume":"27","author":[{"given":"Ahmed M.","family":"Farghaly","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0278-0376","authenticated-orcid":false,"given":"Ola H.","family":"Rizk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inas","family":"Darwish","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria 21521, Egypt"},{"name":"Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"Hamza","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7038-8018","authenticated-orcid":false,"given":"Mezna Saleh","family":"Altowyan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-3201","authenticated-orcid":false,"given":"Assem","family":"Barakat","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"},{"name":"Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Teleb","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","first-page":"e29","article-title":"Heart disease and stroke statistics\u20142015 update: A report from the American Heart Association","volume":"131","author":"Mozaffarian","year":"2015","journal-title":"Circulation"},{"key":"ref_2","unstructured":"World Health Organization (2011). 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