Design and Synthesis of New Sulfonamides-Based Flt3 Inhibitors

Author(s): Reem F. Abutayeh, Jehad Almaliti, Mutasem O. Taha*

Journal Name: Medicinal Chemistry

Volume 16 , Issue 3 , 2020


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Graphical Abstract:


Abstract:

Background: Flt3 is an oncogenic kinase involved in different leukemias. It is most prominently associated with acute myeloid leukemia (AML). Flt3-specific inhibitors have shown promising results in interfering with AML.

Methods: The crystallographic structures of two inhibitors complexed within Flt3, namely, quizartinib and F6M, were used to guide the synthesis of new sulfonamide-based Flt3 inhibitors.

Results: One of the prepared compounds showed low micromolar anti-Flt3 bioactivity, and interestingly, low micromolar bioactivity against the related oncogenic kinase VEGFR2.

Conclusion: Sulfonamides were successfully used as privileged scaffolds for the synthesis of novel Flt3 inhibitors of micromolar potencies.

Keywords: Flt3, Quizatrinib, F6M, Sulfonamides, VEGFR2, Acute Myeloid Leukemia.

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Article Details

VOLUME: 16
ISSUE: 3
Year: 2020
Published on: 17 April, 2020
Page: [403 - 412]
Pages: 10
DOI: 10.2174/1573406415666190401144053
Price: $65

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