Effects of 1-benzylxanthines on cyclic AMP phosphodiesterase 4 isoenzyme.
Based on our results regarding the structure-activity relationships of alkylxanthines and imidazo[2,1-i]purines as phosphodiesterase 4 (PDE4) inhibitors, we designed new 1-benzylxanthines and investigated their PDE4 inhibitory activities. 3,7-Dihydro-7-acetonyl-1-(2,4-dichlorobenzyl)-3-propyl-1H-purine-2,4-dione (2h) exhibited both more selective and more potent PDE4 inhibitory activity than rolipram and XT-611.
Suzuki
Hirokazu
H
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan. h-suzuki@hokuriku-u.ac.jp
Sawanishi
Hiroyuki
H
Nomura
Masaaki
M
Shimada
Tsutomu
T
Miyamoto
Ken-Ichi
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015195:Drug Design; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000201:enzymology; D043264:Phosphodiesterase I / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D007202:Indicators and Reagents; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D014970:Xanthines; D043264:Phosphodiesterase I; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4