Cardiotonic agents. 2. Synthesis and structure-activity relationships in a new class of 6-, 7-, and 8-pyridyl-2(1H)-quinolone derivatives

• Published in: Journal of medicinal chemistry Vol. 29; no. 12; pp. 2433 - 2438
• Main Authors: Leclerc, Gerard, Marciniak, Gilbert, Decker, Nicole, Schwartz, Jean
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-12-1986
• Subjects: Animals; Atrial Function; Cardiotonic Agents - chemical synthesis; Female; Guinea Pigs; Heart Atria - drug effects; In Vitro Techniques; Indicators and Reagents; Male; Myocardial Contraction - drug effects; Pyridines - chemical synthesis; Pyridines - pharmacology; Quinolines - chemical synthesis; Quinolines - pharmacology; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00162a003

A series of 6-, 7-, and 8-pyridyl-2(1H)-quinolone derivatives with various quinolone substitutents (CH3, Cl, OH, OCH3) was prepared by arylation of pyridine with quinolone via a diazotized aminoquinolone for positive inotropic activity. Several derivatives, especially those with a pyridyl ring in the 6-position, were from 28 to 50 times more potent on left guinea pig atria than ARL-115 and milrinone used as references. Intrinsic activities of the derivatives were almost equivalent to that of ARL-115. These results indicate that pyridyl-2(1H)-quinolone derivatives are a potent new class of positive inotropic agents.