title: Phthalazine PDE4 inhibitors. Part 3: the synthesis and in vitro evaluation of derivatives with a hydrogen bond acceptor.
abstract: 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.
authors.affiliation: Inpharzam Ricerche, Zambon Group, Via Ai Soi, 6807, Taverne, Switzerland. mauro.napoletano@zambongroup.com
authors.forename: Mauro
authors.initials: M
authors.lastname: Napoletano
authors.forename: Gabriele
authors.initials: G
authors.lastname: Norcini
authors.forename: Franco
authors.initials: F
authors.lastname: Pellacini
authors.forename: Francesco
authors.initials: F
authors.lastname: Marchini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Morazzoni
authors.forename: Raimondo
authors.initials: R
authors.lastname: Fattori
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Ferlenga
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pradella
mesh_terms: 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
chemical_list: D010726:Phosphodiesterase Inhibitors; D010793:Phthalazines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram