Discovery of novel pyrazolo[1,5-a]pyridine-based EP1 receptor antagonists by scaffold hopping: Design, synthesis, and structure-activity relationships

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