Novel compounds possessing potent cAMP and cGMP phosphodiesterase inhibitory activity. Synthesis and cardiovascular effects of a series of imidazo[1,2-a]quinoxalinones and imidazo[1,5-a]quinoxalinones and their aza analogues.
A series of novel imidazoquinoxalinones and their aza analogues were prepared by the cyclization of o-amino(1H-imidazol-1-yl)aryls and heteroaryls with carbonyldiimidazole. The compounds were screened for inhibition of Type I and Type IV phosphodiesterases (PDE's) and evaluated for their vasorelaxant and positive inotropic activities in vitro. In general, compounds having potent PDE inhibitory activity also possessed good inotropic and vasodilator activity, although linear correlations between these activities could not be established.
Davey
D D
DD
Department of Medicinal Chemistry, Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.
Erhardt
P W
PW
Cantor
E H
EH
Greenberg
S S
SS
Ingebretsen
W R
WR
Wiggins
J
J
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology*; D002316:Cardiotonic Agents; D004285:Dogs; D006321:Heart / Q000187:drug effects; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D015394:Molecular Structure; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology*
D001372:Aza Compounds; D002316:Cardiotonic Agents; D007093:Imidazoles; D011810:Quinoxalines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases