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This study describes the design, synthesis, and evaluation of a series of novel\n                    <jats:italic>N<\/jats:italic>\n                    \u2010Cinnamamide\/benzamide\u2010(4\u2010(substituted phenyl)\u20106\u2010(4\u2010cyclohexylphenyl)pyrimidin\u20102\u2010yl) derivatives (\n                    <jats:bold>Ri\u2013Rxii<\/jats:bold>\n                    ) as EGFR inhibitors. Among these, compound\n                    <jats:bold>Riv<\/jats:bold>\n                    exhibited superior antiproliferative activity against wild\u2010type and mutant EGFR\u2010driven NSCLC cell lines, including EGFR\n                    <jats:sup>L858R\/T790M<\/jats:sup>\n                    and the drug\u2010resistant EGFR\n                    <jats:sup>L858R\/T790M\/C797S<\/jats:sup>\n                    variant, with low IC\n                    <jats:sub>50<\/jats:sub>\n                    values and minimal cytotoxicity towards normal cell lines. Compound\n                    <jats:bold>Riv<\/jats:bold>\n                    effectively induced cell cycle arrest at the S and G2\/M phases and triggered apoptosis, with 54.38% of cells undergoing apoptotic or necrotic death. Additionally,\n                    <jats:bold>Riv<\/jats:bold>\n                    exhibited strong antioxidant activity, outperforming the standard ascorbic acid in DPPH and ABTS assays, indicating its ability to reduce oxidative stress. Molecular docking and dynamic simulation studies confirmed stable binding interactions with key EGFR residues, and DFT analysis revealed favorable electronic properties. Furthermore, in silico ADMET predictions highlighted\n                    <jats:bold>Riv<\/jats:bold>\n                    's promising pharmacokinetic and toxicity profiles, supporting its potential as a safe and effective anticancer agent. This comprehensive evaluation positions\n                    <jats:bold>Riv<\/jats:bold>\n                    as a strong candidate for overcoming drug resistance in NSCLC treatment.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70390","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:10:20Z","timestamp":1788930620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rational Design, Synthesis, Biological Evaluation, and In Silico Study of\n                    <i>N<\/i>\n                    \u2010Cinnamamide\/Benzamide\u2010(4\u2010(Substituted Phenyl)\u20106\u2010(4\u2010Cyclohexylphenyl)pyrimidin\u20102\u2010yl) Derivatives as\n                    <scp>EGFR<\/scp>\n                    Inhibitors Targeting\n                    <scp>\n                      EGFR\n                      <sup>WT<\/sup>\n                    <\/scp>\n                    ,\n                    <scp>\n                      EGFR\n                      <sup>T790M<\/sup>\n                    <\/scp>\n                    , and\n                    <scp>\n                      EGFR\n                      <sup>L858R<\/sup>\n                    <\/scp>\n                    <sup>\n                      \/\n                      <scp>T790M<\/scp>\n                      \/\n                      <scp>C797S<\/scp>\n                    <\/sup>\n                    in\n                    <scp>NSCLC<\/scp>"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2763-5757","authenticated-orcid":false,"given":"Rohit","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Integrated Drug Discovery Centre Acharya &amp; BM Reddy College of Pharmacy  Bengaluru Karnataka 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