Choi, Min Jung Roh, Eun Joo Hur, Wooyoung Lee, So Ha Sim, Taebo Oh, Chang-Hyun Lee, Sun-Hwa Kim, Jong Seung Yoo, Kyung Ho 2024-01-19T21:04:02Z 2024-01-19T21:04:02Z 2021-09-05 2018-12-15 0960-894X https://pubs.kist.re.kr/handle/201004/120570 A novel series of aminopyrimidinylisoindoline derivatives 1a-w having an aminopyrimidine scaffold as a hinge region binding motif were designed and synthesized. Among them, six compounds showed potent inhibitory activities against AXL kinase with IC50 values of submicromolar range. Especially, compound 1u possessing (4-acetylpiperazin-1-yl)phenyl moiety exhibited extremely excellent efficacy (IC50 = < 0.00050 mu M). Their in vitro antiproliferative activities were tested over five cancer cell lines. Most compounds showed good antiproliferative activities against HeLa cell line. The kinase panel profiling of 50 different kinases and the selected inhibitory activities for the representative compound 1u were carried out. The compound 1u exhibited excellent inhibitory activities (IC50 = < 0.00050, 0.025, and 0.050 mu M for AXL, MER, and TYRO3, respectively) against TAM family, together with potent antiproliferative activity against MV4-11 cell line (GI(50) = 0.10 mu M) related to acute myeloid leukemia (AML). English Pergamon Press Ltd. RECEPTOR TYROSINE KINASES TAM FAMILY CANCER TARGETS CELLS Design, synthesis, and biological evaluation of novel aminopyrimidinylisoindolines as AXL kinase inhibitors Article 10.1016/j.bmcl.2018.10.013 1 Bioorganic & Medicinal Chemistry Letters, v.28, no.23-24, pp.3761 - 3765 Bioorganic & Medicinal Chemistry Letters 28 23-24 3761 3765 scie scopus 000453232500033 2-s2.0-85054875418 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article RECEPTOR TYROSINE KINASES TAM FAMILY CANCER TARGETS CELLS Aminopyrimidinylisoindolines Inhibitors AXL kinase TAM family Enzyme inhibitory activity Antiproliferative activity