Document Report Card

ID: ALA1123800

Journal: J Med Chem

Title: Cardiotonic agents. 2. (Imidazolyl)aroylimidazolones, highly potent and selective positive inotropic agents.

Authors: Hagedorn AA, Erhardt PW, Lumma WC, Wohl RA, Cantor E, Chou YL, Ingebretsen WR, Lampe JW, Pang D, Pease CA.

Abstract: A series of 4-alkyl-1,3-dihydro-5-[(1H-imidazolyl)benzoyl]-2H-imidazol-2-ones 9 was synthesized and evaluated in vitro for positive inotropic and cyclic AMP phosphodiesterase inhibitory activity. A wide range of inotropic and enzyme-inhibitory potencies was observed, substitution on the imidazolyl moiety being the major determinant of activity. The 4-ethyl-5-[4-(1H-imidazol-1-yl)benzoyl] congener 9g exhibited the highest potency in vitro. Incorporation of a methyl group at the imidazolyl 2-position gave 9h, which was less potent but remarkably selective in vivo for positive inotropic effects over heart rate and hypotensive effects.

CiteXplore: 3039132

DOI: 10.1021/jm00391a013