Pyridazinone derivatives: design, synthesis, and in vitro vasorelaxant activity
Abouzid, Khaled; Abdel Hakeem, Maha; Khalil, Omnya; Maklad, Yosria;
Abstract
In an attempt to identify potential vasodilator-cardiotonic lead compounds, three series of pyridazinones were designed using three-dimensional pharmacophore developed with CATALYST software from a set of potent cyclic nucleotide phosphodiesterase III, cAMP PDEIII inhibitors. The features of the target compounds were based on the structures of many biologically active lead compounds with cAMP phosphodiesterase III inhibiting activity such as Milrinone and others. Compounds with higher fit scores to the developed pharmacophore were synthesized namely; 6-(3-ethoxycarbonyl-4-oxo-1,4-dihydroquinolin-6-yl)-4,5-dihydro-3(2H)-pyridazinones (3a and 3b), 6-[4-(2,6-disubstituted-quinolin-4-ylamino)phenyl]-4,5-dihydropyridazin-3(2H)-ones (5a-f), and 6-[3-(5-cyano-6-oxo-4-aryl-1,6-dihydro-2-pyridyl)phenylamino]-3(2H)pyridazinone (8a and 8b). The vasodilator activity of the newly synthesized compounds was examined on the isolated main pulmonary artery of the rabbit. Some of the tested compounds showed moderate vasorelaxant activity compared with standard drug, Milrinone.
Other data
Title | Pyridazinone derivatives: design, synthesis, and in vitro vasorelaxant activity | Authors | Abouzid, Khaled ; Abdel Hakeem, Maha; Khalil, Omnya; Maklad, Yosria | Keywords | pyridazinone;quinolone;quinoline;pyridone;vasodilator activity;pharmacophore model;CARDIOTONIC AGENTS;HEART-FAILURE;DIGITALIS;VASODILATOR;SEARCH;POTENT | Issue Date | 1-Jan-2008 | Publisher | PERGAMON-ELSEVIER SCIENCE LTD | Journal | Bioorganic & medicinal chemistry | Volume | 16 | Issue | 1 | Start page | 382 | End page | 389 | ISSN | 0968-0896 | DOI | 10.1016/j.bmc.2007.09.031 | PubMed ID | 17905589 | Scopus ID | 2-s2.0-38049000814 | Web of science ID | WOS:000253345400039 |
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