Pyridazinone derivatives: design, synthesis, and in vitro vasorelaxant activity.
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.
Abouzid
Khaled
K
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt. abouzid@yahoo.com
Abdel Hakeem
Maha
M
Khalil
Omnya
O
Maklad
Yosria
Y
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D058987:Phosphodiesterase 3 Inhibitors; D011651:Pulmonary Artery / Q000187:drug effects; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D058987:Phosphodiesterase 3 Inhibitors; D011724:Pyridazines; D014665:Vasodilator Agents