New imidazo(1,2-a)pyrazine derivatives with bronchodilatory and cyclic nucleotide phosphodiesterase inhibitory activities.
New imidazo[1,2-a]pyrazine derivatives have been synthesized either by direct cyclization from pyrazines or by electrophilic substitutions. The presence of electron donating groups on position 8 greatly enhances the reactivity of the heterocycle towards such reactions on position 3 of the heterocycle. The activities of these derivatives in trachealis muscle relaxation and in inhibiting cyclic nucleotide phosphodiesterase (PDE) isoenzyme types III and IV have been assessed. All compounds demonstrated significantly higher relaxant potency than theophylline. All the derivatives were moderately potent in inhibiting the type IV isoenzyme of PDE but only those with a cyano group on position 2 were potent in inhibiting the type III isoenzyme.
Vitse
O
O
Pharmacochimie & Biomolécules, Laboratoire de Chimie Organique Pharmaceutique, Faculté de Pharmacie, Montpellier, France.
Laurent
F
F
Pocock
T M
TM
Bénézech
V
V
Zanik
L
L
Elliott
K R
KR
Subra
G
G
Portet
K
K
Bompart
J
J
Chapat
J P
JP
Small
R C
RC
Michel
A
A
Bonnet
P A
PA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001993:Bronchodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D001993:Bronchodilator Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011719:Pyrazines; D011725:Pyridines; C080660:6-bromo-8-methylaminoimidazo(1,2-a)pyrazine-2-carbonitrile; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C001439:imidazo(1,2-a)pyridine