Synthesis and biological activities of optically active 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinone (OPC-18790).
The enantiomers of 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinon e (OPC-18790), a novel cardiotonic agent, were synthesized and evaluated for positive inotropic activity. The key intermediates, 2,3-epoxypropoxy derivatives, were obtained by the alkylation of 6-hydroxy-2(1H)-quinolinone with optically active epichlorohydrin and subsequent ring closure. In an in vitro study, the (R)-(+)-isomer was about 10-fold more potent than the (S)-(-)-isomer.
Fujioka
T
T
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Japan.
Teramoto
S
S
Tsujimi
S
S
Takemoto
K
K
Mori
T
T
Hosokawa
T
T
Sumida
T
T
Tominaga
M
M
Yabuuchi
Y
Y
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004285:Dogs; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism
D002316:Cardiotonic Agents; D015363:Quinolones; C077543:toborinone