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At present, three FLT3 inhibitors have been approved, but these drugs are prone to cause resistance after a period of medication. Developing new FLT3 inhibitors with novel structures is an effective strategy to enhance drug treatment efficacy. This study presents an extension of our effort to design and synthesize a series of novel pyrimidine\u20102,4\u2010diamine derivatives as inhibitors of FLT3. The most active compound, <jats:bold>7r<\/jats:bold>, showed significant inhibition against FLT3 with IC<jats:sub>50<\/jats:sub> value of 7.82\u2009nM. In addition, <jats:bold>7r<\/jats:bold> exhibited prominent anticancer activities against AML cell lines, such as MV4\u201011 (IC<jats:sub>50<\/jats:sub>\u2009=\u200946.07\u2009nM) and MOLM\u201013 (IC<jats:sub>50<\/jats:sub>\u2009=\u200951.6\u2009nM). Compound <jats:bold>7r<\/jats:bold> inhibited phosphorylation of FLT3 pathways in a dose\u2010dependent manner in MV4\u201011 cell lines.<\/jats:p>","DOI":"10.1002\/ddr.70119","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T02:51:16Z","timestamp":1750301476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design, Synthesis, and Biological Evaluation of Potent FLT3 Inhibitor for Acute Myeloid Leukemia (AML) Treatment"],"prefix":"10.1002","volume":"86","author":[{"given":"Kun","family":"Du","sequence":"first","affiliation":[{"name":"Henan University of Chinese Medicine Zhengzhou PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"he","sequence":"additional","affiliation":[{"name":"Henan University of Chinese Medicine Zhengzhou PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyang","family":"Fu","sequence":"additional","affiliation":[{"name":"Henan University of Chinese Medicine Zhengzhou PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guimin","family":"Xue","sequence":"additional","affiliation":[{"name":"Henan University of Chinese Medicine Zhengzhou PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-1104","authenticated-orcid":false,"given":"Zhiqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henan University of Chinese Medicine Zhengzhou PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-7867","authenticated-orcid":false,"given":"Xiaokun","family":"Li","sequence":"additional","affiliation":[{"name":"Henan University of Chinese Medicine Zhengzhou PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6066-2231","authenticated-orcid":false,"given":"Yanle","family":"Zhi","sequence":"additional","affiliation":[{"name":"Henan University of Chinese Medicine Zhengzhou PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.5045\/br.2022.2022017"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.103248"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-733196"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-733196"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406184"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199502023320514"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.6.1947.1947_1947_1958"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.063"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00425-3"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2016.50"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-199502030-00004"},{"issue":"1","key":"e_1_2_9_13_1","first-page":"327","article-title":"In Vivo Antitumor Activity of SU11248, a Novel Tyrosine Kinase Inhibitor Targeting Vascular Endothelial Growth Factor and Platelet\u2010Derived Growth Factor Receptors: Determination of a Pharmacokinetic\/Pharmacodynamic Relationship","volume":"9","author":"Mendel D. 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