| 摘要 |
PROBLEM TO BE SOLVED: To provide more selective compounds, e.g., endowed with a higher affinity toward the LPDE4 with respect to the affinity to HPDE4, in order to attenuate or avoid the side effects associated with inhibition of HPDE4, based on the fact that phosphodiesterase 4 (PDE4) exists in two distinct forms representing different conformations, that were designated as high affinity rolipram binding site or HPDE4, especially present in the central nervous system and in parietal cells, and low affinity rolipram binding site or LPDE4 which is found in the immune and inflammatory cells, and that they differ with respect to their sensitivity to inhibitors and side-effects.SOLUTION: Provided are PDE4 inhibitors comprising derivatives of 1-phenyl-2-pyridinyl alkyl alcohols of formula (2) or an N-oxide of the pyridine ring thereof, which are useful for the prevention and/or treatment of any disease characterized by PDE4 overactivity and/or wherein an inhibition of PDE4 activity is desirable. The PDE4 inhibitors of the present invention efficaciously act upon inhalation administration and could be characterized by a good persistency in the lung and a short systemic duration. |
