l-454-560 and Vomiting

l-454-560 has been researched along with Vomiting* in 1 studies

Other Studies

1 other study(ies) available for l-454-560 and Vomiting

Article	Year
Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: structure-activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor. Bioorganic & medicinal chemistry letters, 2005, Dec-01, Volume: 15, Issue:23 The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC(50)<1nM) and also of LPS-induced TNF-alpha release in human whole blood (IC(50)<0.5microM). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC(50)<0.1mg/kg ip) but require a dose of about 10mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound. Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Bronchoconstriction; Cyclic Nucleotide Phosphodiesterases, Type 4; Guinea Pigs; Humans; Inhibitory Concentration 50; Phosphodiesterase Inhibitors; Quinolines; Rats; Saimiri; Sheep; Structure-Activity Relationship; Vomiting	2005

Article

Year

Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: structure-activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor.

Bioorganic & medicinal chemistry letters, 2005, Dec-01, Volume: 15, Issue:23

The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC(50)<1nM) and also of LPS-induced TNF-alpha release in human whole blood (IC(50)<0.5microM). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC(50)<0.1mg/kg ip) but require a dose of about 10mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Bronchoconstriction; Cyclic Nucleotide Phosphodiesterases, Type 4; Guinea Pigs; Humans; Inhibitory Concentration 50; Phosphodiesterase Inhibitors; Quinolines; Rats; Saimiri; Sheep; Structure-Activity Relationship; Vomiting

2005