Cardiotonic agents. 2. Synthesis and structure-activity relationships in a new class of 6-, 7-, and 8-pyridyl-2(1H)-quinolone derivatives.
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.
D000818:Animals; D016275:Atrial Function; D002316:Cardiotonic Agents / Q000138:chemical synthesis*; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D007202:Indicators and Reagents; D011725:Pyridines; D011804:Quinolines