Phosphodiesterase inhibitors. Part 6: design, synthesis, and structure-activity relationships of PDE4-inhibitory pyrazolo[1,5-a]pyridines with anti-inflammatory activity.

Abstract We previously identified KCA-1490 [(−)-6-(7-methoxy-2-trifluoromethyl-pyrazolo[1,5- a ]pyridin-4-yl)-5-methyl-4,5-dihydro-3-(2 H )-pyridazinone], a dual PDE3/4 inhibitor. In the present study, we found highly potent selective PDE4 inhibitors derived from the structure of KCA-1490. Among them, N -(3,5-dichloropyridin-4-yl)-7-methoxy-2-(trifluoromethyl)pyrazolo[1,5- a ]pyridine-4-carboxamide ( 2a ) had good anti-inflammatory effects in an animal model.