Design and Synthesis of New Sulfonamides-Based Flt3 Inhibitors-Reference-Cited by-同舟云学术

Design and Synthesis of New Sulfonamides-Based Flt3 Inhibitors

Published:2020-04-17 Issue:3 Volume:16 Page:403-412
ISSN:1573-4064
Container-title:Medicinal Chemistry
language:en
Short-container-title:MC

Author:

Abutayeh Reem F.¹,Almaliti Jehad²,Taha Mutasem O.²

Affiliation:

1. Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan

2. Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Amman, Jordan

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.

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery

Reference41 articles.

1. Döhner H.; Weisdorf D.; Bloomfield C.; Acute myeloid leukemia. New Engl J Med 2015,373,1136-1152

2. Davies R.; Pierce A.; Forster C.; Grey R.; Xu J.; Arnost M.; Choquette D.; Galullo V.; Tian S.; Henkel G.; Chen G.; Heidary D.; Ma J.; Stuver-Moody C.; Namchuk M.; Design, synthesis, and evaluation of a novel dual fms-like tyrosine kinase 3/stem cell factor receptor (FLT3/c-KIT) inhibitor for the treatment of acute myelogenous leukemia. J Med Chem 2011,54,7184-7192

3. Trujillo A.; McGee C.; Cogle C.; Angiogenesis in acute myeloid leukemia and opportunities for novel therapies. J Oncol 2012,2012,1-9

4. Li Y.; Suppression of leukemia expressing wild-type or ITD-mutant FLT3 receptor by a fully human anti-FLT3 neutralizing antibody. Blood 2004,104,1137-1144

5. Gaul M.D.; Xu G.; Kirkpatrick J.; Ott H.; Baumann C.A.; 4-Amino-6-piperazin-1-yl-pyrimidine-5-carbaldehyde oximes as potent FLT-3 inhibitors. Bioorganic Med Chem Lett 2007,17,4861-4865

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