Spiroquinazolinones as novel, potent, and selective PDE7 inhibitors. Part 2: Optimization of 5,8-disubstituted derivatives.
The optimization of 5,8-disubstituted spirocyclohexane-quinazolinones into potent, selective, soluble PDE7 inhibitors with acceptable in vivo pharmacokinetic parameters is presented.
Bernardelli
Patrick
P
Pfizer Global Research and Development, 3-9 rue de la Loge 94265 Fresnes, France. patrick.bernardelli@aventis.com
Lorthiois
Edwige
E
Vergne
Fabrice
F
Oliveira
Chrystelle
C
Mafroud
Abdel-Kader
AK
Proust
Emmanuelle
E
Pham
Nga
N
Ducrot
Pierre
P
Moreau
François
F
Idrissi
Moulay
M
Tertre
Anita
A
Bertin
Bernadette
B
Coupe
Magali
M
Chevalier
Eric
E
Descours
Arnaud
A
Berlioz-Seux
Françoise
F
Berna
Patrick
P
Li
Mei
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D011799:Quinazolines; D013141:Spiro Compounds; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7