Abstract
Expanding on HTS hit 4 afforded a series of [1,3,5]triazine derivatives as novel PDE4 inhibitors. The SAR development and optimization process with the emphasis on ligand efficiency and physicochemical properties led to the discovery of compound 44 as a potent, selective and orally active PDE4 inhibitor.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Binding Sites
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Cyclic Nucleotide Phosphodiesterases, Type 4 / chemistry
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Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
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Cyclic Nucleotide Phosphodiesterases, Type 7 / antagonists & inhibitors
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Cyclic Nucleotide Phosphodiesterases, Type 7 / metabolism
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Drug Evaluation, Preclinical
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Half-Life
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Microsomes, Liver / metabolism
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Molecular Docking Simulation
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Phosphodiesterase 4 Inhibitors / chemical synthesis
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Phosphodiesterase 4 Inhibitors / chemistry*
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Phosphodiesterase 4 Inhibitors / pharmacokinetics
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Protein Structure, Tertiary
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Rats
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Structure-Activity Relationship
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Triazines / chemical synthesis
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Triazines / chemistry*
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Triazines / pharmacokinetics
Substances
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Phosphodiesterase 4 Inhibitors
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Triazines
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Cyclic Nucleotide Phosphodiesterases, Type 7
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PDE7A protein, human