Journal of Medicinal Chemistry p. 3607 - 3612 (1992)
Update date:2022-08-05
Topics:
Fujioka
Teramoto
Mori
Hosokawa
Sumida
Tominaga
Yabuuchi
A series of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinones has been synthesized and evaluated for positive inotropic activity on the canine heart. Some of these derivatives have a potent activity with none or negative chronotropic effect in isolated, blood-perfused dog heart preparations. They also display a high selectivity for positive inotropic effect over chronotropic and vasodilatory effects in anesthetized dogs. (±)-6-[2- Hydroxy-3-[(3-methoxybenzyl)amino]propoxy]-2(1H)-quinolinone (39) and (±)-6- [3-(3,4-dimethoxybenzyl)amino]-2-hydroxypropoxy]-2(1H)-quinolinone (40) were further investigated in conscious dogs. After iv administration, they did not affect heart rate or mean blood pressure at the dose producing a 50% increase in the peak of the first derivative of the left ventricular pressure. The compounds (39, OPC-18750, and 40, OPC-18790) are the most promising agents with desirable biological activities, and now are currently undergoing clinical evaluation.
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