Document Report Card

ID: ALA1124478

Journal: J Med Chem

Title: Cardiotonic agents. 5. Fragments from the heterocycle-phenyl-imidazole pharmacophore.

Authors: Erhardt PW, Hagedorn AA, Davey D, Pease CA, Venepalli BR, Griffin CW, Gomez RP, Wiggins JR, Ingebretsen WR, Pang D.

Abstract: To examine the role of each component in the heterocycle-phenyl-imidazole inotropic pharmacophore, several imidazolone derivatives, an arylimidazole, a substituted 3,4-dihydro-4-oxopyrimidine, and a quinolin-2(1H)-one derivative were prepared as structural fragments or representatives from this relationship. Tests for cardiac inotropic activity in ferret papillary muscle strips (FPM) and for inhibition of crude cAMP phosphodiesterase obtained from canine cardiac tissue suggest that, while all three components contribute significantly toward potent activity (active at less than 1 microM concentrations in FPM), any combination of two components, in approximately a preferred geometry, represents the minimal requirements for weak activity (active at less than 25 microM concentrations). No single component appears to be requisite in an absolute sense.

CiteXplore: 2542552

DOI: 10.1021/jm00126a005