Design and synthesis of novel imidazo[1,2-a]quinoxalines as PDE4 inhibitors.
New imidazo[1,2-a]quinoxaline derivatives have been synthesised by condensation of an appropriate alpha-aminoalcohol with a quinoxaline followed by intramolecular cyclisation and nucleophilic substitutions. Their phosphodiesterase inhibitory activities have been assessed on a preparation of the PDE4 isoform purified from a human alveolar epithelial cell line (A549). These studies showed potent inhibitory properties that emphasize the importance of a methyl amino group at position 4 and a weakly hindered group at position 1.
Deleuze-Masquéfa
Carine
C
Pharmacochimie et Biomolécules, Laboratoire de Chimie Organique Pharmaceutique, Faculté de Pharmacie, 15, Av. Ch. Flahault, BP 14 491, 34093 Montpellier Cedex 5, France.
Gerebtzoff
Grégori
G
Subra
Guy
G
Fabreguettes
Jean-Roch
JR
Ovens
Annabel
A
Carraz
Maëlle
M
Strub
Marie-Paule
MP
Bompart
Jacques
J
George
Pascal
P
Bonnet
Pierre-Antoine
PA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D002460:Cell Line; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015195:Drug Design; D004847:Epithelial Cells / Q000201:enzymology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D020128:Inhibitory Concentration 50; D008168:Lung / Q000166:cytology; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011810:Quinoxalines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4