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J Med Chem ; 59(5): 1727-46, 2016 Mar 10.
Article in English | MEDLINE | ID: mdl-26800309

ABSTRACT

The discovery of a novel series of therapeutic agents that has been designed and optimized for treating chronic obstructive pulmonary disease is reported. The pharmacological strategy was based on the identification of compounds that inhibit a defined subset of kinase enzymes modulating inflammatory processes that would be effective against steroid refractory disease and exhibit a sustained duration of action after inhaled delivery.


Subject(s)
Asthma/drug therapy , Drug Discovery , Protein Kinase Inhibitors/pharmacology , Protein Kinases/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Animals , Asthma/metabolism , Dose-Response Relationship, Drug , Drug Resistance/drug effects , Humans , Male , Mice , Mice, Inbred Strains , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Pulmonary Disease, Chronic Obstructive/metabolism , Steroids/pharmacology , Structure-Activity Relationship , U937 Cells
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