Structure-activity relationship of quinazolinedione inhibitors of calcium-independent phosphodiesterase.
A series of quinazolinediones and azaquinazolinediones is described which possess potent inhibitory activity toward the calcium-independent phosphodiesterase enzyme (CaIPDE). In vivo testing showed that this in vitro activity translates to animal models predictive of chronic diseases such as depression and inflammation. These results support the hypothesis that inhibition of CaIPDE may lead to useful activity in such chronic diseases.
Lowe
J A
JA
Central Research Division Pfizer, Inc. Groton, Connecticut 06340.
Archer
R L
RL
Chapin
D S
DS
Chen
J B
JB
Helweg
D
D
Johnson
J L
JL
Koe
B K
BK
Lebel
L A
LA
Moore
P F
PF
Nielsen
J A
JA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D008297:Male; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011760:Pyrrolidinones / Q000378:metabolism / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D020889:Rolipram; D013329:Structure-Activity Relationship
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D011799:Quinazolines; D020889:Rolipram