Abstract
Starting from pyrazole HTS hit (1), a series of 1-aryl-1H-indazoles have been synthesized as JNK3 inhibitors with moderate selectivity against JNK1. SAR studies led to the synthesis of 5r as double digital nanomolar JNK3 inhibitor with good in vivo exposure.
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MeSH terms
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Aniline Compounds / chemical synthesis
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Aniline Compounds / chemistry*
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Aniline Compounds / pharmacokinetics
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Animals
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Brain / metabolism
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Drug Design*
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Half-Life
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Indazoles / chemical synthesis
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Indazoles / chemistry*
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Indazoles / pharmacokinetics
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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JNK Mitogen-Activated Protein Kinases / metabolism
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Mitogen-Activated Protein Kinase 10 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 10 / metabolism
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Mitogen-Activated Protein Kinase 8 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 8 / metabolism
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Protein Binding
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacokinetics
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Rats
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Structure-Activity Relationship
Substances
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Aniline Compounds
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Indazoles
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Protein Kinase Inhibitors
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Mitogen-Activated Protein Kinase 10
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 8