title: 3-Acetyl-5-acylpyridin-2(1H)-ones and 3-acetyl-7,8-dihydro-2,5(1H,6H)-quinolinediones: synthesis, cardiotonic activity and computational studies.
abstract: A series of milrinone analogues, namely 6-substituted 3-acetyl-5-acylpyridin-2(1H)-ones 4a-c, e, f and 7-substituted or unsubstituted 3-acetyl-7,8-dihydro-2,5(1H,6H)-quinolinediones 4g-j, in which the cyano group was replaced by the acetyl function, was prepared. In a preliminary pharmacological investigation on spontaneously beating atria from reserpine-treated guinea-pigs, all new compounds did not induce any inotropic effect equivalent or higher than that of the milrinone chosen as the reference compound. In order to rationalise how the structure modifications influence the activity and the selectivity of the title compounds, a computational study has been performed. The important role of the substituents in positions-3 and -6 on the pyridone nucleus has been highlighted.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Genova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Lo Presti
authors.forename: R
authors.initials: R
authors.lastname: Boggia
authors.forename: A
authors.initials: A
authors.lastname: Feltrin
authors.forename: G
authors.initials: G
authors.lastname: Menozzi
authors.forename: P
authors.initials: P
authors.lastname: Dorigo
authors.forename: L
authors.initials: L
authors.lastname: Mosti
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D020105:Milrinone / Q000494:pharmacology; D008968:Molecular Conformation; D009200:Myocardial Contraction / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D018759:Adrenergic Uptake Inhibitors; D002316:Cardiotonic Agents; D011804:Quinolines; D012110:Reserpine; D020105:Milrinone