Abstract
A series of phenylaminopyrimidines has been identified as inhibitors of Janus kinases (JAKs). Development of this initial series led to the potent JAK2/JAK1 inhibitor CYT387 (N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-benzamide). Details of synthesis and SAR studies of these compounds are reported.
MeSH terms
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Animals
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Benzamides / chemical synthesis
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Benzamides / chemistry*
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Benzamides / pharmacology
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Binding Sites
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Caco-2 Cells
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Cell Line, Tumor
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Computer Simulation
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Humans
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Janus Kinase 2 / antagonists & inhibitors*
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Janus Kinase 2 / metabolism
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Male
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / metabolism
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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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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / pharmacokinetics
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Pyrimidines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
Substances
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Benzamides
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Protein Isoforms
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Protein Kinase Inhibitors
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Pyrimidines
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N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
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Janus Kinase 2