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

Publication date: Available online 14 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Kentaro Umei, Yosuke Nishigaya, Atsushi Kondo, Kazuya Tatani, Nobuyuki Tanaka, Yasushi Kohno, Shigeki Seto
Novel pyrazolo[1,5-a]pyridine derivatives were designed, synthesized and evaluated as orally active EP1 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 EP1 antagonist 4c, which exhibited good pharmacological effect through intraduodenal (id) administration in a 17-phenyltrinor prostaglandin E2-induced bladder contraction model in rats.

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