{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:22:49Z","timestamp":1784557369831,"version":"3.55.0"},"reference-count":23,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The synthesis of a molecularly diverse library of tetrasubstituted alkenes containing a barbiturate motif is described. Base-induced condensation of N1-substituted pyrimidine-2,4,6(1H,3H,5H)-triones with 5-(bis(methylthio)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione gave 3-substituted 5-(methylthio)-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones (\u2018pyranopyrimidinones\u2019), regioselectively. A sequence of reactions involving ring-opening of the pyran moiety, displacement of the methylthio group with an amine, re-formation of the pyran ring, and after its final cleavage with an amine, gave tetrasubstituted alkenes (3-amino-3-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)propanamides) with a diversity of substituents. Cleavage of the pyranopyrimidinones with an aniline was facilitated in 2,2,2-trifluoroethanol under microwave irradiation. Compounds were tested against Escherichia coli, Staphylococcus aureus, the yeast Schizosaccharomyces pombe, and the pathogenic fungus Candida albicans. No compounds exhibited activity against E. coli, whilst one compound was weakly active against S. aureus. Three compounds were strongly active against S. pombe, but none was active against C. albicans.<\/jats:p>","DOI":"10.3390\/molecules25245868","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:45:36Z","timestamp":1607906736000},"page":"5868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Diversity via Tetrasubstituted Alkenes Containing a Barbiturate Motif: Synthesis and Biological Activity"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5310-7923","authenticated-orcid":false,"given":"Ahmed","family":"Al-Sheikh","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Petra, P.O. Box 961343, Amman 11196, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masuma","family":"Begum","sequence":"additional","affiliation":[{"name":"BiBerChem Research Ltd., The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bian","family":"Zhang","sequence":"additional","affiliation":[{"name":"BiBerChem Research Ltd., The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Demuris Ltd., The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas E. E.","family":"Allenby","sequence":"additional","affiliation":[{"name":"Demuris Ltd., The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Waddell","sequence":"additional","affiliation":[{"name":"Chemical Crystallography Unit, School of Natural &amp; Environmental Sciences, Bedson Building, Newcastle University, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard T.","family":"Golding","sequence":"additional","affiliation":[{"name":"BiBerChem Research Ltd., The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, UK"},{"name":"School of Natural &amp; Environmental Sciences, Bedson Building, Newcastle University, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165rv13","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden Killers: Human Fungal Infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci. 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