Quinazolines: combined type 3 and 4 phosphodiesterase inhibitors.
A series of quinazolines has been prepared and evaluated for its ability to inhibit cyclic AMP phosphodiesterase type 3, type 4A, 4B and 4D. The most potent inhibitors showed IC50 values in the nanomolar range for type 3 and type 4 isoforms and bind with high affinity to the [3H]rolipram binding site. These quinazolines represent a new family of potent mixed PDE 3/4 inhibitors and are expected to have a therapeutic potential.
Charpiot
B
B
Research, Novartis Pharma AG, Basle, Switzerland. brigitte.charpiot@pharma.novartis.com
Brun
J
J
Donze
I
I
Naef
R
R
Stefani
M
M
Mueller
T
T
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006801:Humans; D020128:Inhibitory Concentration 50; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D010726:Phosphodiesterase Inhibitors; D011799:Quinazolines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4