{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:57:23Z","timestamp":1785488243890,"version":"3.56.0"},"reference-count":73,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A highly efficient aza\u2010Michael addition reaction of 5\u2010amino pyrimidinones with \u03b1, \u03b2\u2010unsaturated olefins under optimized reaction conditions is reported. The resulting functionalized amino\u2010pyrimidinone\u2010based aza\u2010Michael mono\u2010adducts were obtained in good to excellent yields. These synthesized compounds were screened for their anti\u2010inflammatory potential in RAW264.7 macrophages. Among the synthesized compounds, we identified two derivatives,\n                    <jats:bold>3d<\/jats:bold>\n                    and\n                    <jats:bold>3f<\/jats:bold>\n                    , as potent anti\u2010inflammatory compounds. Our findings demonstrated that\n                    <jats:bold>3d<\/jats:bold>\n                    and\n                    <jats:bold>3f<\/jats:bold>\n                    maintained normal cell viability at the bioactive concentrations (1, 5, and 10\u00a0\u00b5M), effectively reduced the production of proinflammatory mediators such as nitric oxide and proinflammatory cytokines including interleukin\u20106 and tumor necrosis factor\u2010\u03b1. In addition, immunoblotting results revealed that\n                    <jats:bold>3d<\/jats:bold>\n                    and\n                    <jats:bold>3f<\/jats:bold>\n                    downregulate the protein expression of i\u2010NOS and COX\u20102 in LPS\u2010activated RAW264.7 macrophages. Furthermore, molecular docking was performed to elucidate the binding mechanism of these compounds and to establish a correlation between the in vitro results and the in silico data. Collectively, our results suggest that\n                    <jats:bold>3d<\/jats:bold>\n                    and\n                    <jats:bold>3f<\/jats:bold>\n                    attenuated the LPS\u2010induced inflammatory response in macrophages and can be a structural lead for the development of novel anti\u2010inflammatory agents.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202502861","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:26:20Z","timestamp":1767867980000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Anti\u2010Inflammatory Activity of Functionalized 1,2,4,5\u2010Tetrasubstituted\u2010Pyrimidinone"],"prefix":"10.1002","volume":"23","author":[{"given":"Rayees Ahmad","family":"Naikoo","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences I.K. Gujral Punjab Technical University  Kapurthala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diljeet","family":"Kumar","sequence":"additional","affiliation":[{"name":"Pharmacology Division CSIR\u2010Indian Institute of Integrative Medicine  Jammu India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nusrit Iqbal","family":"Andrabi","sequence":"additional","affiliation":[{"name":"Pharmacology Division CSIR\u2010Indian Institute of Integrative Medicine  Jammu India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassir","family":"Arfath","sequence":"additional","affiliation":[{"name":"Pharmacology Division CSIR\u2010Indian Institute of Integrative Medicine  Jammu India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemender","family":"Singh","sequence":"additional","affiliation":[{"name":"Schoolof Biotechnology Shri Mata Vashino Devi University  Katra India"},{"name":"Scientist B\u2010ezy Diagnostics Private Limited  Jammu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences I.K. 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