{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T13:45:19Z","timestamp":1777211119585,"version":"3.51.4"},"reference-count":27,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["18-CE18-0009-01"],"award-info":[{"award-number":["18-CE18-0009-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["DMC20181039565"],"award-info":[{"award-number":["DMC20181039565"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation pour la Recherche M\u00e9dicale","award":["18-CE18-0009-01"],"award-info":[{"award-number":["18-CE18-0009-01"]}]},{"name":"Fondation pour la Recherche M\u00e9dicale","award":["DMC20181039565"],"award-info":[{"award-number":["DMC20181039565"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Malaria remains one of the major health problems worldwide. The increasing resistance of Plasmodium to approved antimalarial drugs requires the development of novel antiplasmodial agents that can effectively prevent and\/or treat this disease. Based on the structure of Gamhepathiopine, a 2-tert-butylaminothieno[3,2-d]pyrimidin-4(3H)-one hit, active on the sexual and asexual stages of the parasite and thanked for the introduction of various substituents at position 4 of the thienopyrimidine core by nucleophilic aromatic substitution and pallado-catalyzed coupling reactions, a series of 4-substituted thieno[3,2-d]pyrimidines were identified as displaying in vitro activities against both the erythrocytic stage of P. falciparum and the hepatic stage of P. berghei. Among the 28 compounds evaluated, the chloro analogue of Gamhepathiopine showed good activity against the erythrocytic stage of P. falciparum, moderate toxicity on HepG2, and better activity against hepatic P. berghei parasites, compared to Gamhepathiopine.<\/jats:p>","DOI":"10.3390\/ph15070820","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T20:59:18Z","timestamp":1656968358000},"page":"820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["4-Substituted Thieno[3,2-d]pyrimidines as Dual-Stage Antiplasmodial Derivatives"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-898X","authenticated-orcid":false,"given":"Prisca","family":"Lagard\u00e8re","sequence":"first","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron, UMR 5247, CNRS, Universit\u00e9 de Montpellier, ENSCM, UFR des Sciences Pharmaceutiques et Biologiques, 34293 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1277-7728","authenticated-orcid":false,"given":"Romain","family":"Musti\u00e8re","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Facult\u00e9 de Pharmacie, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-5803","authenticated-orcid":false,"given":"Nadia","family":"Amanzougaghene","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie et des Maladies Infectieuses (CIMI), INSERM, CNRS, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-4039","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Hutter","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, 13005 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Fran\u00e7ois","family":"Franetich","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie et des Maladies Infectieuses (CIMI), INSERM, CNRS, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9075-8303","authenticated-orcid":false,"given":"Nadine","family":"Azas","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, 13005 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9946-829X","authenticated-orcid":false,"given":"Patrice","family":"Vanelle","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Facult\u00e9 de Pharmacie, 13385 Marseille, France"},{"name":"Service Central de la Qualit\u00e9 et de l\u2019Information Pharmaceutiques, AP-HM, H\u00f4pital Conception, 13005 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0238-2447","authenticated-orcid":false,"given":"Pierre","family":"Verhaeghe","sequence":"additional","affiliation":[{"name":"CHU de N\u00eemes, Service de Pharmacie, 30029 N\u00eemes, France"},{"name":"LCC-CNRS, Universit\u00e9 de Toulouse, CNRS UPR 8241, UPS, 31400 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-6039","authenticated-orcid":false,"given":"Nicolas","family":"Primas","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Facult\u00e9 de Pharmacie, 13385 Marseille, France"},{"name":"Service Central de la Qualit\u00e9 et de l\u2019Information Pharmaceutiques, AP-HM, H\u00f4pital Conception, 13005 Marseille, 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