Discovery of thiadiazoles as a novel structural class of potent and selective PDE7 inhibitors. Part 2: metabolism-directed optimization studies towards orally bioavailable derivatives.
The synthesis and optimization of pharmacokinetic parameters of structurally novel small PDE7 inhibitors is discussed.
Vergne
Fabrice
F
Pfizer Global Research and Development, 3-9 Rue de la loge 94265 Fresnes, France. fabrice.vergne@aventis.com
Bernardelli
Patrick
P
Lorthiois
Edwige
E
Pham
Nga
N
Proust
Emmanuelle
E
Oliveira
Chrystelle
C
Mafroud
Abdel-Kader
AK
Ducrot
Pierre
P
Wrigglesworth
Roger
R
Berlioz-Seux
Françoise
F
Coleon
Francis
F
Chevalier
Eric
E
Moreau
François
F
Idrissi
Moulay
M
Tertre
Anita
A
Descours
Arnaud
A
Berna
Patrick
P
Li
Mei
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*
D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D013830:Thiadiazoles; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7