Quaternary substituted PDE4 inhibitors I: the synthesis and in vitro evaluation of a novel series of oxindoles.
The following letter presents the synthesis and in vitro evaluation of a novel quaternary substituted series of phosphodiesterase type (IV) (PDE4) inhibitors. The compounds represent conformationally constrained analogues of the Celltech PDE IV inhibitor, CDP 840. Examples with sub-micromolar IC50's for PDE4 inhibition are reported.
Hulme
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C
Rhône-Poulenc Rorer Central Research, Collegeville, PA 19426, USA.
Poli
G B
GB
Huang
F C
FC
Souness
J E
JE
Djuric
S W
SW
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; C102660:CDP 840; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4