| Autor: |
Duplantier, A. J., Andresen, C. J., Cheng, J. B., Cohan, V. L., Decker, C., DiCapua, F. M., Kraus, K. G., Johnson, K. L., Turner, C. R., UmLand, J. P., Watson, J. W., Wester, R. T., Williams, A. S., Williams, J. A. |
| Zdroj: |
Journal of Medicinal Chemistry; June 18, 1998, Vol. 41 Issue: 13 p2268-2277, 10p |
| Abstrakt: |
High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent than 11 with IC50 values of 0.03−1.6 μM. One such compound, CP-220,629 (22) (IC50 = 0.44 μM), was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 2.0 mg/kg, po) and demonstrated a significant reduction in eosinophil (55%), neutrophil (65%), and IL-1β (82%) responses to antigen challenge in atopic monkeys (10 mg/kg, po). |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
