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.
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
Royer
Frederique
F
Wrigglesworth
Roger
R
Schellhaas
Jennifer
J
Barvian
Mark
M
Moreau
François
F
Idrissi
Moulay
M
Tertre
Anita
A
Bertin
Bernadette
B
Coupe
Magali
M
Berna
Patrick
P
Soulard
Patricia
P
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