Abstract
A novel series of benzodiazepine derivatives have been discovered as inhibitors of PDE4 enzymes. We have found that our compounds are selective versus other PDE enzymes, and that the activity can be modulated by specific structural modifications. One compound exhibited a strong eosinophilic infiltration inhibiting action on sensitized Brown-Norway rats (compound 9, 5.1 mg/kg p.o.), moreover this compound is not emetic at 3 mg/kg i.v.
MeSH terms
-
3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
-
Animals
-
Benzodiazepines / chemical synthesis*
-
Benzodiazepines / pharmacology*
-
Binding Sites
-
Cyclic Nucleotide Phosphodiesterases, Type 4
-
Dogs
-
Guinea Pigs
-
Humans
-
Indoles / chemical synthesis
-
Indoles / pharmacology
-
Inhibitory Concentration 50
-
Phosphodiesterase Inhibitors / chemical synthesis*
-
Phosphodiesterase Inhibitors / pharmacology*
-
Rats
-
Rats, Inbred BN
-
Rats, Wistar
-
Rolipram / metabolism
-
Rolipram / pharmacology
-
Stereoisomerism
-
Structure-Activity Relationship
-
Substrate Specificity
-
U937 Cells
Substances
-
Indoles
-
Phosphodiesterase Inhibitors
-
Benzodiazepines
-
3',5'-Cyclic-AMP Phosphodiesterases
-
Cyclic Nucleotide Phosphodiesterases, Type 4
-
Rolipram