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

Autor: Umei K; Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan., Nishigaya Y; Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan., Kondo A; Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Azumino, Nagano 399-8304, Japan., Tatani K; Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Azumino, Nagano 399-8304, Japan., Tanaka N; Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Azumino, Nagano 399-8304, Japan., Kohno Y; Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan., Seto S; Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan. Electronic address: shigeki.seto@mb.kyorin-pharm.co.jp.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2017 May 01; Vol. 25 (9), pp. 2635-2642. Date of Electronic Publication: 2017 Mar 14.
DOI: 10.1016/j.bmc.2017.03.003
Abstrakt: 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.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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