3-Acetyl-5-acylpyridin-2(1 H)-ones and 3-acetyl-7,8-dihydro-2,5(1H,6H)-quinolinediones: Synthesis, cardiotonic activity and computational studies

Farmaco

Volumn 54, Issue 7, 1999, Pages 465-474

  Lo Presti, Eleonora ^a   Boggia, Raffaella ^a   Feltrin, Antonio ^b   Menozzi, Giulia ^a   Dorigo, Paola ^c   Mosti, Luisa ^a  

^a UNIVERSITY OF GENOA   (Italy)

^b Tecnofarmaci SCpA   (Italy)

^c UNIVERSITY OF PADOVA   (Italy)

Author keywords

Chronotropic activity; Inotropic activity; Molecular electrostatic potentials (MEPS); Pyridone derivatives; Quinolinediones derivatives

Indexed keywords

CARDIOTONIC AGENT; MILRINONE; PYRIDONE DERIVATIVE; QUINOLINE DERIVATIVE;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; GUINEA PIG; HEART ATRIUM; INOTROPISM; MALE; NONHUMAN;

ADRENERGIC UPTAKE INHIBITORS; ANIMALS; CARDIOTONIC AGENTS; CHEMISTRY, PHYSICAL; CRYSTALLOGRAPHY, X-RAY; GUINEA PIGS; MALE; MILRINONE; MOLECULAR CONFORMATION; MYOCARDIAL CONTRACTION; QUINOLINES; RESERPINE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033618568     PISSN: 0014827X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0014-827X(99)00053-1     Document Type: Article

References (22)

1. Alousi A.A., Canter J.M., Montenaro M.J., Fort D.J., Ferrari R.A. Cardiotonic activity of milrinone, a new and potent cardiac bipyridine, on the normal and failing heart of experimental animals. J. Cardiovasc. Pharmacol. 5:1983;792-803.
2. Alousi A.A., Heltosky A. Amrinone: a positive inotropic agent with a direct vasodilatatory activity in the canine isolated perfused hind limb preparation. Fed. Proc. 39:1980;855-861.
3. Mosti L., Schenone P., Menozzi G. Reaction of 2-dimethylamino-methylene-1,3-diones with dinucleophiles. V. Synthesis of 5-acyl-1,2-dihydro-2-oxo-3-pyridinecarbonitriles and 1,2,5,6,7,8-hexahydro-2,5-dioxo-3-quinolinecarboxamides. J. Heterocycl. Chem. 22:1985;1503-1509.
4. Dorigo P., Gaion R.M., Belluco P., Fraccarollo D., Maragno I., Bombieri G., Benetollo F., Mosti L., Orsini F. A pharmacological, crystallographic and quantum chemical study of new inotropic agents. J. Med. Chem. 36:1993;2475-2484.
5. Mosti L., Boggia R., Fossa P. 2-Pyridone derivatives as inotropic agents: synthesis, pharmacology and molecular modeling study. Farmaco. 52:1997;331-337.
6. Fossa P., Boggia R., Lo Presti E., Mosti L., Dorigo P., Floreani M. Inotropic agents. Synthesis and structure-activity relationships of new milrinone related cAMP PDE III inhibitors. Farmaco. 52:1997;523-530.
7. Dorigo P., Gaion R.M., Belluco P., Borea P.A., Guerra L., Mosti L., Floreani M., Carpenedo F. Antagonism towards endogenous adenosine and inhibition of cGI-PDE in the cardiac effects of amrinone, milrinone and related analogues. Gen. Pharmacol. 23:1992;535-541.
8. Moos H.W., Humblet C.C., Sircar I., Rithner C., Weishaar R.E., Bristol J.A., McPhail A.T. Cardiotonic agents. 8. Selective inhibitors of adenosine 3′,5′-cyclic phosphate phosphodiesterase III. Elaboration of a five-point model for positive inotropic activity. J. Med. Chem. 30:1987;1963-1972.
9. Erhardt P.W., Hagedorn A.A. III M. Sabio, Cardiotonic agents. 3. A topographical model of the cardiac cAMP phosphodiesterase receptor. Mol. Pharmacol. 33:1988;1-13.
10. Fossa P., Boggia R., Mosti L. Toward the identification of the cardiac cGMP inhibited-phosphodiesterase catalytic site. J. Comput. Aided Mol. Des. 12:1998;1-12.
11. Mosti L., Schenone P., Iester M., Dorigo P., Gaion R.M., Fraccarollo D. Synthesis and cardiotonic activity of esters of 2-substituted 5-acetyl-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids. Eur. J. Med. Chem. 28:1993;853-858.
12. Dorigo P., Fraccarollo D., Santostasi G., Gaion R.M., Maragno I., Floreani M., Carpenedo F., Iester M., Mosti L., Schenone P. Pharmacological characterization of a new milrinone analogue. Farmaco. 49:1994;19-23.
13. Schenone P., Mosti L., Menozzi G. Reaction of 2-dimethylamino-methylene-1,3-diones with dinucleophiles. I. Synthesis of 1,5-disubstituted 4-acylpyrazoles. J. Heterocycl. Chem. 19:1982;1355-1361.
14. Tetsuzo K., Masaki N. Studies on ketene and its derivatives. LXXVI. Reactions of aceto-acetamide and β-aminocrotonamide with β-diketene, β-ketoaldehyde and related compounds. Chem. Pharm. Bull. 24:1976;303-309.
15. R.E. Buckles, A. Langsjoen, L. Mueller, I. Svendsen, The synthesis and proof of structure of 2,4-dimethyl-6-hydroxynicotinamide, Proc. Minn. Acad. Sci. 26 (1958) 257-258; Chem. Abstr. 54 (1960) 24724b.
16. R.E. Buckles, A. Langsjoen, L. Mueller, I. Svendsen, The synthesis and proof of structure of 2,4-dimethyl-6-hydroxynicotinamide, Proc. Minn. Acad. Sci. 26 (1958) 257-258; Chem. Abstr. 54 (1960) 24724b.
17. Apaya R.A., Lucchese B., Price S.L., Vinter J.G. The matching of electrostatic extrema: a useful method in drug design? A study of phosphodiesterase III inhibitors. J. Comput. Aided Mol. Des. 9:1995;33-43.
18. MacroModel, Version 5.5, Columbia University, New York, 1996.
19. HyperChem, Release 5.0, Hypercube Inc., Gainesville, FL, 1996.
20. Gaussian-94 (Revision A.1), M.J. Frisch, G.W. Trucks, H.B. Schlegel, P.M.W. Gill, B.G. Johnson, M.A. Robb, J.R. Cheeseman, T.A. Keith, G.A. Petersson, J.A. Montgomery, K. Raghavachari, M.A. Al-laham, V.G. Zakrzewski, J.V. Ortiz, J.B. Foresman, J. Cioslowski, B.B. Stefanov, A. Nanayakkara, M. Challacombe, C.Y. Peng, P.Y. Ayala, W. Chen, M.W. Wong, J.L. Andres, E.S. Replogle, R. Gomperts, R.L. Martin, D.J. Fox, J.S. Binkley, D.J. Defrees, J. Baker, J.P. Stewart, M. Head-Gordon, C. Gonzalez, J.A. Pople, Gaussian Inc., Pittsburgh, PA, 1995.
21. Cody V. Structures of two active inotropic cardiac agents: milrinone [5-cyano-2-methyl-(3,4′-bipyridin)-6(1H)-one] (I) and amrinone [5-amino-(3,4′-bipyridin)-6(1H)-one] (II). Acta Crystallogr., Sect. C. 43:1987;1325.
22. SYBYL, Version 6.3, Tripos Inc., St. Louis, MO 62117, 1996.