Discovery of novel pyrazolo[1,5-a]pyridine-based EP receptor antagonists by scaffold hopping: Design, synthesis, and structure-activity relationships.

A scaffold-hopping strategy towards a new pyrazolo[1,5-a]pyridine based core using molecular hybridization of two structurally distinct EP antagonists, followed by structure-activity relationship-guided optimization, resulted in the identification of potent EP antagonists exemplified by 4c, 4f, and 4j, which were shown to reduce pathological intravesical pressure in rats when administered at 1mg/kg iv.