Pyridazinone derivatives: design, synthesis, and in vitro vasorelaxant activity
| Autor: | Maha Abdel Hakeem, Yosria Maklad, Omnya Khalil, Khaled A.M. Abouzid |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cardiotonic Agents
Molecular model Stereochemistry Vasodilator Agents Clinical Biochemistry Pharmaceutical Science Pulmonary Artery Phosphodiesterase 3 Inhibitors Biochemistry Chemical synthesis chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Animals Enzyme Inhibitors Molecular Biology Cyclic nucleotide phosphodiesterase Chemistry Organic Chemistry Quinoline Phosphodiesterase Biological activity Pyridazines Vasodilation Molecular Medicine Milrinone Rabbits Pharmacophore medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry. 16(1) |
| ISSN: | 1464-3391 |
| Popis: | 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(2 H )-pyridazinones ( 3a and 3b ), 6-[4-(2,6-disubstituted-quinolin-4-ylamino)phenyl]-4,5-dihydropyridazin-3(2 H )-ones ( 5a – f ), and 6-[3-(5-cyano-6-oxo-4-aryl-1,6-dihydro-2-pyridyl)phenylamino]-3(2 H )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. |
| Databáze: | OpenAIRE |
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