title: Synthesis and cardiotonic activity of 2-substituted 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids and their methyl or ethyl esters.
abstract: The synthesis of ethyl or methyl esters of 5-cyano-1,6-dihydro-6-oxo-3- pyridinecarboxylic acids carrying as 2-substituent a polar group such as CO2C2H5, (CH2)2CO2CH3, (CH2)3CO2C2H5, CH2OCH3, or CF3 group is described. Also 2-[5-cyano-1,6-dihydro-2-(1,1-dimethylethyl)-6-oxo-3-pyridyl]-2- oxoacetic acid and 2,5,6,8-tetrahydro-2,5-dioxo-1H-thiopyrano[3,4-b]pyridine-3-carbon itrile were prepared. Nearly all the above esters gave routinely the corresponding carboxylic acids by alkaline hydrolysis followed by acidification. As milrinone analogues, the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria from reserpine-treated guinea-pigs. 5-Cyano-2-trifluoromethyl-1,6- dihydro-6-oxo-3-pyridinecarboxylic acid and, in a lesser degree, the relative ethyl ester showed an appreciable positive inotropic activity, although inferior to that of milrinone.
authors.affiliation: Istituto di Scienze Farmaceutiche dell'Università, Genova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Mosti
authors.forename: G
authors.initials: G
authors.lastname: Menozzi
authors.forename: P
authors.initials: P
authors.lastname: Schenone
authors.forename: P
authors.initials: P
authors.lastname: Dorigo
authors.forename: R M
authors.initials: RM
authors.lastname: Gaion
authors.forename: P
authors.initials: P
authors.lastname: Belluco
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects; D009539:Nicotinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D009539:Nicotinic Acids; D011728:Pyridones; D012110:Reserpine; D020105:Milrinone