Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1′-{6-[5-(pyridin-3-ylmethyl)-1, 3, 4-oxadiazol-2-yl] pyridazin-3-yl}-5-( …

…, T Deguchi, M Yamada, N Watanabe, M Konishi…

Index: Uto, Yoshikazu; Kiyotsuka, Yohei; Ueno, Yuko; Miyazawa, Yuriko; Kurata, Hitoshi; Ogata, Tsuneaki; Deguchi, Tsuneo; Yamada, Makiko; Watanabe, Nobuaki; Konishi, Masahiro; Kurikawa, Nobuya; Takagi, Toshiyuki; Wakimoto, Satoko; Kono, Keita; Ohsumi, Jun Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 2 p. 746 - 754

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Citation Number: 19

Abstract

Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1′-{6-[5-(pyridin-3-ylmethyl)-1, 3, 4-oxadiazol-2-yl] pyridazin-3-yl}-5-(trifluoromethyl)- 3, 4-dihydrospiro [chromene-2, 4′-piperidine](19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6J mice). With ...