Pharmacological evaluation of novel (6-aminopyridin-3-yl)(4-(pyridin-2-yl)piperazin-1-yl) methanone derivatives as TRPV4 antagonists for the treatment of pain

Autor: Narumi Horita, Daiki Nagamatsu, Yasuhide Morioka, Miki Tanimura, Gaku Sakaguchi, Azusa Nozu, Yasuyoshi Iso, Toshiyuki Kanemasa, Natsue Yamanada, Mikie Hinata, Toshiyuki Asaki, Masayuki Imai, Hidetoshi Matsuda, Kenji Takaya, Osamu Yoshida, Hiromi Nakai, Akira Yukimasa, Shinji Suzuki, Masahiko Soga, Naoki Tsuno, Tomoyuki Ogawa, Hiroki Yamaguchi, Miyuki Yamamoto, Satoko Funaki, Motohiro Fujiu
Rok vydání: 2017
Předmět:
Zdroj: Bioorganic & Medicinal Chemistry. 25:2177-2190
ISSN: 0968-0896
DOI: 10.1016/j.bmc.2017.02.047
Popis: A novel series of (6-aminopyridin-3-yl)(4-(pyridin-2-yl)piperazin-1-yl) methanone derivatives were identified as selective transient receptor potential vanilloid 4 (TRPV4) channel antagonist and showed analgesic effect in Freund's Complete Adjuvant (FCA) induced mechanical hyperalgesia model in guinea pig and rat. Modification of right part based on the compound 16d which was disclosed in our previous communication led to the identification of compound 26i as a flagship compound. In this paper, we described the details about design, synthesis and structure-activity relationship (SAR) analysis at right and left part of these derivatives (Fig. 1).
Databáze: OpenAIRE
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