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Novel positive inotropic agents: synthesis and biological activities of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone derivatives. 1992

T Fujioka, and S Teramoto, and T Mori, and T Hosokawa, and T Sumida, and M Tominaga, and Y Yabuuchi
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Company, Ltd., Japan.

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.

UI MeSH Term Description Entries
D008297 Male Males
D002316 Cardiotonic Agents Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE). Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015363 Quinolones A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID. Ketoquinoline,Ketoquinolines,Oxoquinoline,Oxoquinolines,Quinolinone,Quinolinones,Quinolone

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