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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Design and Synthesis of New Sulfonamides-Based Flt3 Inhibitors

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

Volume 16, Issue 3, 2020

Page: [403 - 412] Pages: 10

DOI: 10.2174/1573406415666190401144053

Price: $65

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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