- 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-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine]
-
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/6 J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6 J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3 mg/kg) in our preliminary analysis.
- 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
-
scheme or table
p. 746 - 754
(2010/06/11)
-
- Potent 3-spiropiperidine growth hormone secretagogues
-
Systematic SAR studies of the different regioisomers and homologues of the spiro(indane-1,4'-piperidine) moiety in the growth hormone secretagogue L-162,752 are presented. Among them, spiro(3H-1-benzopyran-2,3'-piperidine) was found to afford secretagogue
- Yang, Lihu,Morriello, Greg,Prendergast, Kristine,Cheng, Kang,Jacks, Tom,Chan, Wanda W.-S.,Schleim, Klaus D.,Smith, Roy G.,Patchett, Arthur A.
-
p. 107 - 112
(2007/10/03)
-