Phthalazine PDE4 inhibitors. Part 3: the synthesis and in vitro evaluation of derivatives with a hydrogen bond acceptor.
This communication describes the synthesis and in vitro evaluation of a novel and potent series of phthalazine phosphodiesterase type (IV) (PDE4) inhibitors. The interaction with two distinct polar binding sites allowed us to eliminate the cyclopentyloxy substitution from rolipram-like analogues.
Napoletano
Mauro
M
Inpharzam Ricerche, Zambon Group, Via Ai Soi, 6807, Taverne, Switzerland. mauro.napoletano@zambongroup.com
Norcini
Gabriele
G
Pellacini
Franco
F
Marchini
Francesco
F
Morazzoni
Gabriele
G
Fattori
Raimondo
R
Ferlenga
Pierpaolo
P
Pradella
Lorenzo
L
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006860:Hydrogen Bonding; D009504:Neutrophils / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020889:Rolipram / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship
D010726:Phosphodiesterase Inhibitors; D010793:Phthalazines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram