Design, synthesis and Structure-activity relationship studies of new thiazole-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes
详细信息 查看全文
- 作者：Zheng Lia ; Qianqian Qiua ; Xue Xub ; Xuekun Wanga ; Lei Jiaoa ; Xin Sua ; Miaobo Pana ; Wenlong Huanga ; c ; ydhuangwenlong@126.com" class="auth_mail" title="E-mail the corresponding author ; Hai Qiana ; c ; qianhai24@163.com" class="auth_mail" title="E-mail the corresponding author
- 关键词：FFA1 agonist ; GPR40 ; Liver toxicity ; Type 2 diabetes ; Heteroaromatics ; Dihedral angle
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：4 May 2016
- 年：2016
- 卷：113
- 期：Complete
- 页码：246-257
- 全文大小：2872 K
文摘
- class="listitem" id="list_ulist0010">
- class="label">•
11 heterocycles were synthesized to improve the lipophilicity of TAK-875.
- class="label">•
The methyl group in our thiazole core occupied a crucial hydrophobic subpocket.
- class="label">•
The agonistic activity revealed a good correlation with the dihedral angle.
- class="label">•
class="boldFont">44 revealed lower risk of liver toxicity compared with TAK-875.
- class="label">•
class="boldFont">44 showed lower risk of hypoglycemia compared to first-line drug glibenclamide.