4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable stearoyl-CoA desaturase-1 (SCD1) inhibitors: Part 2. Pyridazine-based analogs

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• 作者：Shyh-Ming Yang ; ^{shyhyang99@yahoo.com" class="auth_mail} ; Yuting Tang ; Thomas Rano ; Huajun Lu ; Gee-Hong Kuo ; Michael D. Gaul ; Yaxin Li ; George Ho ; Wensheng Lang ; James G. Conway ; Yin Liang ; James M. Lenhard ; Keith T. Demarest ; William V. Murray
• 关键词：Stearoyl-CoA desaturase ; SCD1 inhibitors ; Desaturation index ; obesity
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：1 March, 2014
• 年：2014
• 卷：24
• 期：5
• 页码：1437-1441
• 全文大小：2863 K

文摘

Design, synthesis, and biological evaluation of pyridazine-based, 4-bicyclic heteroaryl-piperidine derivatives as potent stearoyl-CoA desaturase-1 (SCD1) inhibitors are described. In a chronic study of selected analog (3e) in Zucker fa/fa (ZF) rat, dose-dependent decrease of body weight gain and plasma fatty acid desaturation index (DI) in both C16 and C18 are also demonstrated. The results indicate that the plasma fatty acid DI may serve as an indicator for direct target engagement and biomarker for SCD1 inhibition.