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

Autor: Nishigaya Y; Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan., Umei K; Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan., Saito Y; Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan., Watanabe H; Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan., Kondo T; Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Azumino, Nagano 399-8304, Japan., Kondo A; Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Azumino, Nagano 399-8304, Japan., Kawamura N; 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., Kohno Y; Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan., Tanaka N; Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Azumino, Nagano 399-8304, 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 letters [Bioorg Med Chem Lett] 2017 Sep 01; Vol. 27 (17), pp. 4044-4050. Date of Electronic Publication: 2017 Jul 25.
DOI: 10.1016/j.bmcl.2017.07.055
Abstrakt: 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 1mg/kg iv.
(Copyright © 2017. Published by Elsevier Ltd.)
Databáze: MEDLINE
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