Cell permeability as a parameter for lead generation in the protein Tyrosine kinase inhibition field.
Based on the inverse relationship between polar surface area and cell permeability and capitalizing on the properties of pyrrolopyrimidines 1 as protein tyrosine kinase inhibitors, pyrrolopyridones 2 were designed and synthesized as potential leads for the development of novel inhibitors with improved cell permeability properties.
Papageorgiou
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C
Novartis Pharma AG, WSJ350.3.14, CH-4002 Basel, Switzerland. christos.papageorgiou@pharma.novartis.com
Camenisch
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G
Borer
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D000818:Animals; D001692:Biological Transport; D002463:Cell Membrane Permeability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011728:Pyridones / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D055672:Static Electricity; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011728:Pyridones; D011505:Protein-Tyrosine Kinases