Uto, Yoshikazu and Ogata, Tsuneaki and Kiyotsuka, Yohei and Miyazawa, Yuriko and Ueno, Yuko and Kurata, Hitoshi and Deguchi, Tsuneo and Yamada, Makiko and Watanabe, Nobuaki and Takagi, Toshiyuki and Wakimoto, Satoko and Okuyama, Ryo and Konishi, Masahiro and Kurikawa, Nobuya and Kono, Keita and Osumi, Jun (2009) Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part II: Identification of 4-ethylamino-3-(2-hydroxyethoxy)-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide and its biological evaluation. Bioorganic & Medicinal Chemistry Letters, 19 (15). pp. 4459-4466.
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Official URL: http://www.sciencedirect.com/science/article/B6TF9...
The continuing investigation of SAR studies of 3-(2-hydroxyethoxy)-N-(5-benzylthiazol-2-yl)-benzamides as stearoyl-CoA desaturase-1 (SCD-1) inhibitors is reported. Our prior hit-to-lead effort resulted in the identification of 1a as a potent and orally efficacious SCD-1 inhibitor. Further optimization of the structural motif resulted in the identification of 4-ethylamino-3-(2-hydroxyethoxy)-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (37c) with sub nano molar IC50 in both murine and human SCD-1 inhibitory assays. This compound demonstrated a dose-dependent decrease in the plasma desaturation index in C57BL/6J mice on a non-fat diet after 7 days of oral administration.
|Uncontrolled Keywords:||SCD-1 inhibitors; Thiazole; Desaturation index|
|Subjects:||Biomedical Science > Nanomedicine|
|Deposited On:||05 Aug 2009 09:36|
|Last Modified:||05 Aug 2009 09:36|
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