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 analogs

• Published in: Journal of medicinal chemistry 1991-09, Vol.34 (9), p.2671-2677
• Main Authors: Davey, David D, Erhardt, P. W, Cantor, E. H, Greenberg, S. S, Ingebretsen, W. R, Wiggins, J
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors; Animals; Aza Compounds - chemistry; Aza Compounds - pharmacology; Cardiotonic Agents; Chemistry; Dogs; Exact sciences and technology; Heart - drug effects; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Imidazoles - chemistry; Imidazoles - pharmacology; In Vitro Techniques; Molecular Structure; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Organic chemistry; Preparations and properties; Quinoxalines - chemistry; Quinoxalines - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00113a002

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.