{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:24:13Z","timestamp":1788272653256,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ischemic stroke gravely endangers human health. To develop novel drugs with antiplatelet and neuroprotective functions for ischemic stroke, edaravone derivatives\n                    <jats:bold>CT01\u2013CT20<\/jats:bold>\n                    , containing 6\u2010(4\u2010aminophenyl)\u20104,5\u2010dihydropyridazin\u20103(2\n                    <jats:italic>H<\/jats:italic>\n                    )\u2010one, were synthesized from materials like dimethyl butynedioate, ethyl acetoacetate, and diethyl 1,3\u2010acetonedicarboxylate,\n                    <jats:italic>via<\/jats:italic>\n                    cyclization, hydrolysis, and condensation. Among them,\n                    <jats:bold>CT16<\/jats:bold>\n                    exhibited outstanding antiplatelet activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 6.72 \u00b5M), absent in edaravone. It also surpassed edaravone in 1,1\u2010diphenyl\u20102\u2010picrylhydrazyl radical scavenging (EC\n                    <jats:sub>50<\/jats:sub>\n                    = 30.80 \u00b5M) and protecting PC12 cells from H\u2082O\u2082 damage. In vivo,\n                    <jats:bold>CT16<\/jats:bold>\n                    effectively reduced carotid artery thrombosis in rats and enhanced blood flow. In the middle cerebral artery occlusion reperfusion injury model, it shrank infarct size, improved neurological scores, increased cerebral blood flow, and lessened brain edema. Preliminary safety tests indicated\n                    <jats:bold>CT16<\/jats:bold>\n                    didn't alter rat blood biochemistry or organ pathology, with a low bleeding risk as an antiplatelet agent. Molecular docking suggested it may inhibit phosphodiesterase 3A to achieve an antiplatelet effect. In conclusion,\n                    <jats:bold>CT16<\/jats:bold>\n                    has both antiplatelet aggregation and neuroprotective effects and is a potential candidate compound for the treatment of ischemic stroke.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202500516","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T22:44:07Z","timestamp":1745534647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design and Synthesis of Edaravone Derivatives Containing 6\u2010(4\u2010aminophenyl)\u20104,5\u2010dihydropyridazin\u20103(2\n                    <i>H<\/i>\n                    )\u2010one as Bifunctional Anti\u2010ischemic Stroke Agents"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0643-4322","authenticated-orcid":false,"given":"Yi","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine &amp; School of Pharmaceutical Sciences Guizhou Medical University Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine &amp; School of Pharmaceutical Sciences Guizhou Medical University Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine &amp; School of Pharmaceutical Sciences Guizhou Medical University Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine &amp; School of Pharmaceutical Sciences Guizhou Medical University Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine &amp; 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