Benzyloxybenzaldehyde analogues as novel adenylyl cyclase activators.
Several benzyloxybenzaldehyde analogues were prepared and found to have significant inhibitory activity toward neutrophil superoxide formation. Consequently, these compounds were evaluated for cAMP-elevating capability. Among them, benzyloxybenzaldehyde (7), exhibiting activity equivalent to forskolin, was determined as an adenylyl cyclase activator since it elevates cAMP levels by activation of adenylyl cyclase but not by inhibition of phosphodiesterase. Having a chemical structure very different from known adenylyl cyclase activators, compound 7 is recommended by us for use as a new lead compound in the future development of adenylyl cyclase activators.
Chang
C
C
Graduate Institute of Pharmaceutical Chemistry, China Medical College, 404, Taichung, Taiwan, ROC.
Kuo
S
S
Lin
Y
Y
Wang
J
J
Huang
L
L
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000819:agonists*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020128:Inhibitory Concentration 50; D009504:Neutrophils / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000037:antagonists & inhibitors*
D001547:Benzaldehydes; D013481:Superoxides; D005576:Colforsin; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; C032175:benzaldehyde