Expanding the structural diversity of diarylureas as multi-target tyrosine kinase inhibitors |
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| Institution: | 1. Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, PR China;2. School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi Province, PR China;1. UCIBIO-REQUIMTE, Chemistry Department, Faculty of Sciences and Technology, Universidade NOVA de Lisboa, 2829?516 Caparica, Portugal;2. ProteoMass Scientific Society, MadanPark, Rua dos Inventores s/n, Monte de Caparica, 2829-516 Caparica, Portugal;3. Department of Nephrology, Hospital Garcia da Orta, Almada, Portugal;4. SING Group, Informatics Department, Higher Technical School of Computer Engineering, University of Vigo, Ourense, Spain;1. Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland;2. Department of Physicochemical Drug Analysis, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland;1. Pharmazeutisches Institut, Abteilung Pharmazeutische Biologie, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, 24118, Kiel, Germany;2. Botanisches Institut, Abteilung Biochemische Ökologie und Molekulare Evolution, Christian-Albrechts-Universität zu Kiel, Am Botanischen Garten 1-9, 24118, Kiel, Germany |
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| Abstract: | Recently approved multi-target inhibitors of receptor tyrosine kinases (RTKs) have significantly improved the clinical treatment of cancers. A series of N,N′-diarylureas incorporated with aromatic heterocycle have been designed, synthesized and evaluated as novel multi-target RTK inhibitors. The preliminary biological evaluation indicated that several compounds exhibited comparable potency with Sorafenib. Among them, compound 6f was identified as the most potent multikinase inhibitor of EGFR, KDR and FGFR1 with IC50 values of 14.83 nM, 21.57 nM, and 28.23 nM, respectively. These compounds expanded the structural diversity of diarylureas as RTK inhibitors. The results demonstrated that compound 6f could be served as novel lead compound for further development of multi-target RTK inhibitors. |
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| Keywords: | Diarylurea Multi-target Receptor tyrosine kinase Inhibitor Structural diversity |
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