Discovery of thiadiazoles as a novel structural class of potent and selective PDE7 inhibitors. Part 1: design, synthesis and structure-activity relationship studies.
The synthesis and SAR studies of a series of structurally novel small molecule inhibitors of PDE7 are discussed. The best compounds from the series displayed low nanomolar inhibitory activity and are selective versus PDE4.
Pfizer Global Research and Development, 3-9 Rue de la loge 94265 Fresnes, France. fabrice.vergne@aventis.com
Fabrice
F
Vergne
Patrick
P
Bernardelli
Edwige
E
Lorthiois
Nga
N
Pham
Emmanuelle
E
Proust
Chrystelle
C
Oliveira
Abdel-Kader
AK
Mafroud
Frederique
F
Royer
Roger
R
Wrigglesworth
Jennifer
J
Schellhaas
Mark
M
Barvian
François
F
Moreau
Moulay
M
Idrissi
Anita
A
Tertre
Bernadette
B
Bertin
Magali
M
Coupe
Patrick
P
Berna
Patricia
P
Soulard
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D013830:Thiadiazoles; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7