Cardiotonic agents. 2. Synthesis and structure-activity relationships of 4,5-dihydro-6-[4-(H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones: a new class of positive inotropic agents

Journal of Medicinal Chemistry
1985.0

Abstract

A series of 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and related compounds were synthesized and evaluated for positive inotropic activity. Most members of this series produced dose-related increases in myocardial contractility that were associated with relatively minor increases in heart rate and decreases in systemic arterial blood pressure. Introduction of a methyl substituent at the 5-position of 1 (CI-914) produced the most potent compound in this series (11, CI-930). Compound 1 is more potent than amrinone whereas compound 11 is more potent than milrinone. The inotropic effects of 1 and 11 are not mediated via stimulation of beta-adrenergic receptors. Selective inhibition of cardiac phosphodiesterase fraction III represents the principal component of the positive inotropic action of 1 and 11.

Knowledge Graph

Similar Paper

Cardiotonic agents. 2. Synthesis and structure-activity relationships of 4,5-dihydro-6-[4-(H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones: a new class of positive inotropic agents
Journal of Medicinal Chemistry 1985.0
Cardiotonic agents. 1. 4,5-Dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones: novel positive inotropic agents for the treatment of congestive heart failure
Journal of Medicinal Chemistry 1984.0
Cardiotonic agents. 7. Inhibition of separated forms of cyclic nucleotide phosphodiesterase from guinea pig cardiac muscle by 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and related compounds. Structure-activity relationships and correlation with in vivo positive inotropic activity
Journal of Medicinal Chemistry 1987.0
A novel class of cardiotonics. Synthesis and pharmacological properties of [4-(substituted-amino)phenyl]pyridazinones and related derivatives
Journal of Medicinal Chemistry 1987.0
Cardiotonic agents. 9. Synthesis and biological evaluation of a series of (E)-4,5-dihydro-6-[2-[4-(1H-imidazol-1-yl)phenyl]ethenyl]-3(2H)-pyridazinones: a novel class of compounds with positive inotropic, antithrombotic, and vasodilatory activities for the treatment of congestive heart failure
Journal of Medicinal Chemistry 1989.0
Cardiotonic agents. 2. Synthesis and structure-activity relationships in a new class of 6-, 7-, and 8-pyridyl-2(1H)-quinolone derivatives
Journal of Medicinal Chemistry 1986.0
Cardiotonic agents. 1. Synthesis and structure-activity relationships in a new class of 3-, 4- and 5-pyridyl-2(1H)-quinolone derivatives
Journal of Medicinal Chemistry 1986.0
4-Aroyl-1,3-dihydro-2H-imidazol-2-ones, a new class of cardiotonic agents
Journal of Medicinal Chemistry 1982.0
Dihydropyridazinone cardiotonics: synthesis and inotropic activity of 5'-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-spiro[cycloalkane-1,3'-[3H]indol]-2'(1'H)-ones
Journal of Medicinal Chemistry 1987.0
Synthesis and cardiotonic activity of novel biimidazoles
Journal of Medicinal Chemistry 1990.0