{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T19:59:23Z","timestamp":1792958363884,"version":"4.5.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2025CXPT129"],"award-info":[{"award-number":["2025CXPT129"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404457"],"award-info":[{"award-number":["82404457"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023MH190"],"award-info":[{"award-number":["ZR2023MH190"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2024QH177"],"award-info":[{"award-number":["ZR2024QH177"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.bioorg.2026.110360","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:07:01Z","timestamp":1786633621000},"page":"110360","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["1,4,5,6-Tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidine derivatives as anti-neuroinflammatory agents: Design, synthesis, and preliminary biological evaluation"],"prefix":"10.1016","volume":"181","author":[{"given":"De-Li","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Sen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Ge","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.bioorg.2026.110360_bb0005","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12974-022-02565-0","article-title":"Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer\u2019s disease","volume":"19","author":"Singh","year":"2022","journal-title":"J. Neuroinflammation"},{"issue":"3","key":"10.1016\/j.bioorg.2026.110360_bb0010","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?","volume":"17","author":"Leng","year":"2020","journal-title":"Nat. Rev. Neurol."},{"issue":"11","key":"10.1016\/j.bioorg.2026.110360_bb0015","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/s41577-025-01188-9","article-title":"A role for microglia in mediating the microbiota\u2013gut\u2013brain axis","volume":"25","author":"Keane","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.bioorg.2026.110360_bb0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108656","article-title":"Discovery of a novel polyketide-derived ferroptosis inhibitor from endophytic fungus Ophiobolus cirsii LZU-1509 with therapeutic potential in ischemic stroke","volume":"163","author":"Xi","year":"2025","journal-title":"Bioorg. Chem."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110360_bb0025","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12974-025-03428-0","article-title":"Microglia efferocytosis: an emerging mechanism for the resolution of neuroinflammation in Alzheimer's disease","volume":"22","author":"Chen","year":"2025","journal-title":"J. Neuroinflammation"},{"issue":"1","key":"10.1016\/j.bioorg.2026.110360_bb0030","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.bioorg.2026.110360_bb0035","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"issue":"6753","key":"10.1016\/j.bioorg.2026.110360_bb0040","doi-asserted-by":"crossref","DOI":"10.1126\/science.adx0043","article-title":"Neuroinflammation across neurological diseases","volume":"388","author":"Shi","year":"2025","journal-title":"Science"},{"issue":"5","key":"10.1016\/j.bioorg.2026.110360_bb0045","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.stem.2023.03.017","article-title":"Advancing cell therapy for neurodegenerative diseases","volume":"30","author":"Temple","year":"2023","journal-title":"Cell Stem Cell"},{"issue":"4","key":"10.1016\/j.bioorg.2026.110360_bb0050","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.cmet.2013.09.010","article-title":"Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging","volume":"18","author":"Youm","year":"2013","journal-title":"Cell Metab."},{"issue":"12","key":"10.1016\/j.bioorg.2026.110360_bb0055","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.tibs.2016.09.002","article-title":"Mechanism and regulation of NLRP3 inflammasome activation","volume":"41","author":"He","year":"2016","journal-title":"Trends Biochem. Sci."},{"issue":"40","key":"10.1016\/j.bioorg.2026.110360_bb0060","doi-asserted-by":"crossref","first-page":"eadi8343","DOI":"10.1126\/sciadv.adi8343","article-title":"Deficient chaperone-mediated autophagy facilitates LPS-induced microglial activation via regulation of the p300\/NF-\u03baB\/NLRP3 pathway","volume":"9","author":"Wu","year":"2023","journal-title":"Sci. Adv."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110360_bb0065","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12974-025-03506-3","article-title":"Modulation of neuronal \u03b11-adrenergic receptor reduces tauopathy and neuroinflammation by inhibiting the STING\/NF-\u03baB\/NLRP3 signaling pathway in Alzheimer\u2019s disease mice","volume":"22","author":"Li","year":"2025","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.bioorg.2026.110360_bb0070","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.bbi.2016.12.014","article-title":"Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-\u03b2 and cognitive function in APP\/PS1 mice","volume":"61","author":"Dempsey","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.bioorg.2026.110360_bb0075","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2021.111405","article-title":"A nuclear factor-kappa B inhibiting peptide suppresses innate immune receptors and gliosis in a transgenic mouse model of Alzheimer\u2019s disease","volume":"138","author":"Lindsay","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.bioorg.2026.110360_bb0080","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108934","article-title":"Discovery of natural compounds and their derivatives against neuroinflammation: pharmacological mechanisms and structure-activity relationship","volume":"165","author":"Xin","year":"2025","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2026.110360_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2024.107819","article-title":"Recent advances in the natural product analogues for the treatment of neurodegenerative diseases","volume":"153","author":"Zhang","year":"2024","journal-title":"Bioorg. Chem."},{"issue":"5","key":"10.1016\/j.bioorg.2026.110360_bb0090","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.tetlet.2003.11.098","article-title":"Synthesis of heliannuol D, an allelochemical from Helianthus annus","volume":"45","author":"Sabui","year":"2004","journal-title":"Tetrahedron Lett."},{"issue":"8","key":"10.1016\/j.bioorg.2026.110360_bb0095","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1021\/ol400781b","article-title":"Benzophenones from an endophytic fungus, Graphiopsis chlorocephala, from Paeonia lactiflora cultivated in the presence of an NAD+-dependent HDAC inhibitor","volume":"15","author":"Teigo","year":"2013","journal-title":"Org. Lett."},{"issue":"5","key":"10.1016\/j.bioorg.2026.110360_bb0100","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1021\/acs.jnatprod.5b01119","article-title":"(\u00b1)-Japonicols A\u2013D, acylphloroglucinol-based meroterpenoid enantiomers with anti-KSHV activities from Hypericum japonicum","volume":"79","author":"Hu","year":"2016","journal-title":"J. Nat. Prod."},{"issue":"6","key":"10.1016\/j.bioorg.2026.110360_bb0105","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1002\/anie.201912489","article-title":"Synthesis and target identification of benzoxepane derivatives as potential anti-neuroinflammatory agents for ischemic stroke","volume":"59","author":"Gao","year":"2019","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.bioorg.2026.110360_bb0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115688","article-title":"Discovery of anti-neuroinflammatory agents from 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidin-2-amine derivatives by regulating microglia polarization","volume":"259","author":"Yang","year":"2023","journal-title":"Eur. J. Med. Chem."},{"issue":"2","key":"10.1016\/j.bioorg.2026.110360_bb0115","doi-asserted-by":"crossref","DOI":"10.1002\/asia.202300937","article-title":"Molecular reconstruction with stereochemical relay: an investigation into the rearrangement of spiro[4.5]decadienone to benzoxepane","volume":"19","author":"Sittihan","year":"2023","journal-title":"Chem. Asian J."},{"issue":"3","key":"10.1016\/j.bioorg.2026.110360_bb0120","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/j.2042-7158.1984.tb06935.x","article-title":"AD-1590, a potent antagonist of lipopolysaccharide-induced fever in rabbits","volume":"36","author":"Hideo","year":"1984","journal-title":"J. Pharm. Pharmacol."},{"issue":"31","key":"10.1016\/j.bioorg.2026.110360_bb0125","doi-asserted-by":"crossref","first-page":"8024","DOI":"10.1002\/chem.200600540","article-title":"Diversity-oriented approach to biologically relevant molecular frameworks starting with \u03b2-naphthol and using the Claisen rearrangement and olefin metathesis as key steps","volume":"12","author":"Kotha","year":"2006","journal-title":"Chem. A Eur. J."},{"issue":"19","key":"10.1016\/j.bioorg.2026.110360_bb0130","doi-asserted-by":"crossref","first-page":"9046","DOI":"10.1021\/acs.joc.6b01691","article-title":"The synthesis of 5-amino-dihydrobenzo[b]oxepines and 5-amino-dihydrobenzo[b]azepines via Ichikawa rearrangement and ring-closing metathesis","volume":"81","author":"Chwastek","year":"2016","journal-title":"J. Org. Chem."},{"issue":"24","key":"10.1016\/j.bioorg.2026.110360_bb0135","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.1021\/acs.orglett.2c01760","article-title":"Total synthesis of pentaketide ansamycin microansamycin H","volume":"24","author":"Sittihan","year":"2022","journal-title":"Org. Lett."},{"issue":"24","key":"10.1016\/j.bioorg.2026.110360_bb0140","doi-asserted-by":"crossref","first-page":"10257","DOI":"10.1021\/jm501100b","article-title":"Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA Approved Pharmaceuticals","volume":"57","author":"Vitaku","year":"2014","journal-title":"J. Med. Chem."},{"issue":"14","key":"10.1016\/j.bioorg.2026.110360_bb0145","doi-asserted-by":"crossref","first-page":"11622","DOI":"10.1021\/acs.jmedchem.4c01122","article-title":"An update on the nitrogen heterocycle compositions and properties of U.S. FDA-Approved Pharmaceuticals (2013\u22122023)","volume":"67","author":"Marshall","year":"2024","journal-title":"J. Med. Chem."},{"issue":"10","key":"10.1016\/j.bioorg.2026.110360_bb0150","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1002\/cmdc.201600132","article-title":"Fluorine scan of inhibitors of the cysteine protease human cathepsin L: dipolar and quadrupolar effects in the \u03c0-stacking of fluorinated phenyl rings on peptide amide bonds","volume":"11","author":"Giroud","year":"2016","journal-title":"ChemMedChem"},{"issue":"3","key":"10.1016\/j.bioorg.2026.110360_bb0155","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1074\/jbc.M109.024844","article-title":"The novel calcineurin inhibitor CN585 has potent immunosuppressive properties in stimulated human T cells","volume":"285","author":"Erdmann","year":"2010","journal-title":"J. Biol. Chem."},{"issue":"19","key":"10.1016\/j.bioorg.2026.110360_bb0160","doi-asserted-by":"crossref","first-page":"4620","DOI":"10.1016\/j.bmc.2016.07.068","article-title":"2-(4-Fluorophenyl)-quinazolin-4(3H)-one as a novel tyrosinase inhibitor: synthesis, inhibitory activity, and mechanism","volume":"24","author":"Wang","year":"2016","journal-title":"Bioorg. Med. Chem."},{"issue":"3","key":"10.1016\/j.bioorg.2026.110360_bb0165","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1021\/acs.jmedchem.5c02359","article-title":"Metabolic stability of fluorinated small molecules: a physical organic chemistry perspective","volume":"69","author":"Bhattarai","year":"2026","journal-title":"J. Med. Chem."},{"issue":"10","key":"10.1016\/j.bioorg.2026.110360_bb0170","doi-asserted-by":"crossref","DOI":"10.1016\/j.cclet.2023.108236","article-title":"A novel vanadium complex VO(p-dmada) inhibits neuroinflammation induced by lipopolysaccharide","volume":"34","author":"He","year":"2023","journal-title":"Chin. Chem. Lett."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110360_bb0175","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1186\/s12951-024-02681-4","article-title":"Exosomes as therapeutic and drug delivery vehicle for neurodegenerative diseases","volume":"22","author":"Nouri","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"10.1016\/j.bioorg.2026.110360_bb0180","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108490","article-title":"Diterpenes as nitric oxide secretion inhibitors from Kaempferia koratensis rhizomes","volume":"160","author":"Kongwaen","year":"2025","journal-title":"Bioorg. Chem."},{"issue":"4","key":"10.1016\/j.bioorg.2026.110360_bb0185","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/j.apsb.2022.11.016","article-title":"Recent advances in diverse nanosystems for nitric oxide delivery in cancer therapy","volume":"13","author":"Gao","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"issue":"8","key":"10.1016\/j.bioorg.2026.110360_bb0190","doi-asserted-by":"crossref","first-page":"743","DOI":"10.3390\/antiox9080743","article-title":"ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease","volume":"9","author":"Simpson","year":"2020","journal-title":"Antioxidants (Basel)"},{"issue":"3","key":"10.1016\/j.bioorg.2026.110360_bb0195","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.apsb.2022.09.023","article-title":"Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia: suppression of neuroinflammation by blocking NF-\u03baB transcription regulation and activating cAMP\/CREB axis","volume":"13","author":"Zhou","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"issue":"1","key":"10.1016\/j.bioorg.2026.110360_bb0200","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41392-020-00312-6","article-title":"Targeting NF-\u03baB pathway for the therapy of diseases: mechanism and clinical study","volume":"5","author":"Yu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"issue":"4","key":"10.1016\/j.bioorg.2026.110360_bb0205","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41423-025-01275-w","article-title":"NLRP3 inflammasome in neuroinflammation and central nervous system diseases","volume":"22","author":"Xu","year":"2025","journal-title":"Cell. Mol. Immunol."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206826008965?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206826008965?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:10:35Z","timestamp":1791407435000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206826008965"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":41,"alternative-id":["S0045206826008965"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2026.110360","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"1,4,5,6-Tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidine derivatives as anti-neuroinflammatory agents: Design, synthesis, and preliminary biological evaluation","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2026.110360","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"110360"}}