Abstract
A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells.
Copyright © 2012. Published by Elsevier Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amines / chemistry*
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Amines / pharmacology
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Humans
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Mice
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Molecular Structure
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology
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Pyrazoles / chemistry*
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Structure-Activity Relationship
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Xenograft Model Antitumor Assays
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fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*
Substances
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Amines
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Pyrazoles
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pyrazole
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fms-Like Tyrosine Kinase 3