l-791943 and Vomiting

l-791943 has been researched along with Vomiting* in 1 studies

Other Studies

1 other study(ies) available for l-791943 and Vomiting

Article	Year
Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors. Bioorganic & medicinal chemistry letters, 2003, Feb-24, Volume: 13, Issue:4 The synthesis and the biological evaluation of new potent phosphodiesterase type 4 (PDE4) inhibitors are presented. This new series was elaborated by replacement of the metabolically resistant phenyl hexafluorocarbinol of L-791,943 (1) by a substituted aminopyridine residue. The structure-activity relationship of N-substitution on 3 led to the identification of (-)-3n which exhibited a good PDE4 inhibitor activity (HWB-TNFalpha=0.12 microM) and an improved pharmacokinetic profile over L-791,943 (rat t(1/2)=2 h). (-)-3n was well tolerated in ferret with an emetic threshold of 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig (54%, 0.1 mg/kg, ip) as well as the ascaris-induced bronchoconstriction model in sheep (64%/97%, early/late, 0.5 mg/kg, iv). Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Aminopyridines; Animals; Bronchoconstriction; Cyclic Nucleotide Phosphodiesterases, Type 4; Drug Evaluation, Preclinical; Enzyme Inhibitors; Ferrets; Guinea Pigs; Half-Life; Humans; Inhibitory Concentration 50; Rats; Sheep; Structure-Activity Relationship; Therapeutic Equivalency; Tumor Necrosis Factor-alpha; Vomiting	2003

Article

Year

Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.

Bioorganic & medicinal chemistry letters, 2003, Feb-24, Volume: 13, Issue:4

The synthesis and the biological evaluation of new potent phosphodiesterase type 4 (PDE4) inhibitors are presented. This new series was elaborated by replacement of the metabolically resistant phenyl hexafluorocarbinol of L-791,943 (1) by a substituted aminopyridine residue. The structure-activity relationship of N-substitution on 3 led to the identification of (-)-3n which exhibited a good PDE4 inhibitor activity (HWB-TNFalpha=0.12 microM) and an improved pharmacokinetic profile over L-791,943 (rat t(1/2)=2 h). (-)-3n was well tolerated in ferret with an emetic threshold of 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig (54%, 0.1 mg/kg, ip) as well as the ascaris-induced bronchoconstriction model in sheep (64%/97%, early/late, 0.5 mg/kg, iv).

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Aminopyridines; Animals; Bronchoconstriction; Cyclic Nucleotide Phosphodiesterases, Type 4; Drug Evaluation, Preclinical; Enzyme Inhibitors; Ferrets; Guinea Pigs; Half-Life; Humans; Inhibitory Concentration 50; Rats; Sheep; Structure-Activity Relationship; Therapeutic Equivalency; Tumor Necrosis Factor-alpha; Vomiting

2003