A novel class of cardiotonics. Synthesis and pharmacological properties of [4-(substituted-amino)phenyl]pyridazinones and related derivatives

Abstract

A series of [4-(substituted-amino)phenyl]pyridazinones and [4-(substituted-methyl)amino]phenyl]pyridazinones was synthesized and evaluated for inotropic activity in vitro and for cardiohemodynamic effects in vivo. Above all, 6-[4-(4-pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride (4, MCI-154) and 6-[4-(4-pyridylamino)phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone hydrochloride (5) showed extremely potent positive inotropic activity along with vasodilating activity. Regarding dP/dtmax (an indicator for cardiac contractility), ED30's (doses that increased dP/dtmax by 30%) of compounds 4 and 5 were 8.5 +/- 1.9 and 4.4 +/- 0.6 micrograms/kg, respectively, where that of amrinone was 471.9 +/- 94.1 micrograms/kg. Structure-activity relationships of these series are presented, and a plausible model of receptor binding is discussed.

Ultrasound and Ionic Liquid: An Ideal Combination for Organic Transformations

“…Pyridazinones and related compounds showed significant biological efficacies that include antiasthmatic, antidepressant, antibacterial, antifongic, analgesic, anti‐inflammatory, antianemic, nephrotropic, anticancer, platelet aggregation inhibition etc activities. Zare et al .…”

Synthesis and Antitubercular Activity of Pyridazinone Derivatives

“…The compounds, 1 and 2, were synthesized according to the reported method [14]. (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Compounds (3-18) were synthesized from 3-(4-chloro/methyl benozyl) propionic acid (1,2) following literature method [14].…”

“…Differently substituted pyridazinones have been found to have potential antibacterial, antifungal and antiviral including anti-HIV activities [1][2][3][4]. Various 3-(2H)-pyridazinone derivatives have shown anticancer [4], analgesic & anti-inflammatory [4][5][6], anticonvulsant [7], cardiotonic & hypotensive [8,9] and antiulcer activities [10].…”

Synthesis of new 4,5-3(2H)pyridazinone derivatives and their cardiotonic, hypotensive, and platelet aggregation inhibition activities

“…Two Pharmacophore models were constructed, one for the cardiotonic activity and the other for the hypotensive one. Construction of the models was based on the reported active compounds (Thyes et al, 1983;Okushiima et al, 1987). The aim of this approach is to gain useful insights into ligand receptor interactions, to identify pharmacophoric structural features of the active ligands, and to use this model for searching molecular databases in order to find new structural categories, a process known as virtual screening.…”