Abstract
Anaplastic lymphoma kinase (ALK) is a highly attractive therapeutic target for the treatment of some non-small cell lung cancer patients. This Letter describes the further SAR exploration on the novel 3-sulfonylpyrazol-4-amino pyrimidine scaffold. This work identified a compound 53 with very good in vitro/in vivo efficacies, good DMPK properties together with better hERG tolerability and it is currently being profiled for the evaluation as a potential pre-clinical candidate.
Keywords:
ALK; Anti-tumor; Kinase; NSCLC; Pyrimidine.
Copyright © 2016 Elsevier Ltd. All rights reserved.
MeSH terms
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Anaplastic Lymphoma Kinase
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Animals
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Antineoplastic Agents / chemical synthesis
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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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Cell Proliferation / drug effects
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Dogs
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Dose-Response Relationship, Drug
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Drug Design*
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Drug Screening Assays, Antitumor
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Humans
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Mice
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Models, Molecular
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Molecular Structure
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Neoplasms, Experimental / drug therapy
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Neoplasms, Experimental / pathology
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Pyrazoles / chemical synthesis*
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Pyrazoles / chemistry
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Pyrazoles / pharmacology*
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Rats
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
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Receptor Protein-Tyrosine Kinases / metabolism
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Structure-Activity Relationship
Substances
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3-sulfonylpyrazol-4-amino pyrimidine
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Pyrazoles
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Pyrimidines
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ALK protein, human
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Alk protein, mouse
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Alk protein, rat
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Anaplastic Lymphoma Kinase
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Receptor Protein-Tyrosine Kinases