Novel pyrazolo[1,5-a]pyridines as orally active EP1 receptor antagonists: Synthesis, structure-activity relationship studies, and biological evaluation

Abstract Novel pyrazolo[1,5- a ]pyridine derivatives were designed, synthesized and evaluated as orally active EP 1 antagonists for the treatment of overactive bladder. Matched molecular pair analysis (MMPA) allowed the design of a new series of pyrazolo[1,5- a ]pyridine derivatives 4 – 6 . Structure-activity relationships (SAR) studies of 4 – 6 were performed, leading to identification of the nanomolar-level EP 1 antagonist 4c , which exhibited good pharmacological effect through intraduodenal (id) administration in a 17-phenyltrinor prostaglandin E2-induced bladder contraction model in rats.