Abstract
The optimization of 5,8-disubstituted spirocyclohexane-quinazolinones into potent, selective, soluble PDE7 inhibitors with acceptable in vivo pharmacokinetic parameters is presented.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
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3',5'-Cyclic-AMP Phosphodiesterases / classification
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3',5'-Cyclic-AMP Phosphodiesterases / metabolism
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Animals
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Biological Availability
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Cell Line
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Cyclic Nucleotide Phosphodiesterases, Type 7
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Half-Life
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Humans
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In Vitro Techniques
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Isoenzymes / antagonists & inhibitors*
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Isoenzymes / classification
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Isoenzymes / metabolism
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Microsomes / drug effects
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Microsomes / metabolism
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Phosphodiesterase Inhibitors / chemistry*
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Phosphodiesterase Inhibitors / pharmacokinetics*
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Quinazolines / chemical synthesis*
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Quinazolines / chemistry
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Quinazolines / pharmacology
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Rats
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology
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Structure-Activity Relationship
Substances
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Isoenzymes
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Phosphodiesterase Inhibitors
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Quinazolines
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Spiro Compounds
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 7