Abstract
The optimization of compounds from the 3-amido-4-anilinoquinolines series of CSF-1R kinase inhibitors is described. The series has excellent activity and kinase selectivity. Excellent physical properties and rodent PK profiles were achieved through the introduction of cyclic amines at the quinoline 6-position. Compounds with good activity in a mouse PD model measuring inhibition of pCSF-1R were identified.
MeSH terms
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Amines / chemistry
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Chemistry, Pharmaceutical / methods*
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels / metabolism
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Humans
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Inhibitory Concentration 50
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Kinetics
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Mice
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Models, Chemical
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Neoplasms / drug therapy*
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Quinolines / chemistry*
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Quinolines / pharmacokinetics*
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Rats
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Receptor, Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
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Receptor, Macrophage Colony-Stimulating Factor / chemistry*
Substances
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Amines
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Antineoplastic Agents
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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Protein Kinase Inhibitors
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Quinolines
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Receptor, Macrophage Colony-Stimulating Factor