Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole derivatives: novel series of PDE4 inhibitors.
This communication describes the synthesis and in vitro PDE4 inhibitory activity of a novel series of imidazol-2-one and 2-cyanoiminoimidazole derivatives. The compounds described were also tested in in vivo models to evaluate their anti-inflammatory activity after topical administration as well as their gastro-intestinal side effects. Several compounds proved to be potent PDE4 inhibitors and some 2-cyanoiminoimidazoles showed less pronounced gastro-intestinal side effects than reference compounds but maintained anti-inflammatory activity after topical administration.
Andrés
J Ignacio
JI
Janssen-Cilag, Basic Research Centre, Jarama s/n, 45007, Toledo, Spain. iandres@prodes.jnj.com
Alonso
José M
JM
Díaz
Adolfo
A
Fernández
Javier
J
Iturrino
Laura
L
Martínez
Pedro
P
Matesanz
Encarna
E
Freyne
Eddy J
EJ
Deroose
Frederik
F
Boeckx
Gustaaf
G
Petit
Davy
D
Diels
Gaston
G
Megens
Anton
A
Somers
Marijke
M
Van Wauwe
Jean
J
Stoppie
Paul
P
Cools
Marina
M
De Clerck
Fred
F
Peeters
Danielle
D
de Chaffoy
Didier
D
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004427:Ear Diseases / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D051381:Rats; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; C117197:imidazolone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4