42075-28-5Relevant articles and documents
Synthesis and structure-activity relationships of cis-tetrahydrophthalazinone/pyridazinone hybrids: A novel series of potent dual PDE3/PDE4 inhibitory agents
Van der Mey, Margaretha,Bommelé, Kirsten M.,Boss, Hildegard,Hatzelmann, Armin,Van Slingerland, Mike,Sterk, Geert J.,Timmerman, Hendrik
, p. 2008 - 2016 (2003)
In this study, the synthesis and in vitro and in vivo pharmacological investigations of a new series of phthalazinone/pyridazinone hybrids with both PDE3 and PDE4 inhibitory activities are described. These compounds combine the pharmacophores of recently discovered 4a,5,8,-8a-tetrahydro-2H-phthalazin-1-one-type inhibitors of PDE4 and the well-known 2H-pyridazin-3-one-type PDE3 inhibitors such as the tetrahydrobenzimidazoles. Most of the synthesized compounds are pharmacologically spoken PDE3/PDE4 hybrids. All hybrids show potent PDE4 inhibitory activity (pIC50 = 7.0-8.7), whereas the pIC50 values for inhibition of PDE3 vary from 5.4 to 7.5. In general, analogues with a 5-methyl-4,5-dihydropyridazinone moiety exhibit the highest PDE3 inhibitory activities. The highest in vivo antiinflammatory activity is displayed by phthalazinones 43 and 44 showing, at a dose of 30μmol/kg po, 46% inhibition of arachidonic acid (AA) induced mouse ear edema. No correlation was found between the in vitro PDE3 and/or PDE4 inhibitory activity and the in vivo antiinflammatory capacity after oral dosing.
6-Phenyl-1,2,4-triazolo[4,3-b]pyridazine hypotensive agents
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, (2008/06/13)
This disclosure describes novel substituted 6-phenyl-1,2,4-triazolo[4,3-b]pyridazines useful as hypotensive agents.
