A novel class of apical sodium-dependent bile salt transporter inhibitors: 1-(2,4-bifluoropheny1)-7-dialkylamino-1,8-naphthyridine-3-carboxamides

作者：Liu, Hongtao; Pang, Guoxun; Ren, Jinfeng; Zhao, Yue; Wang, Juxian^*

来源：Acta Pharmaceutica Sinica B, 2017, 7(2): 223-229.

DOI：10.1016/j.apsb.2016.11.005

• ASBT inhibitors
• Bile acids
• 1-(2,4-Bifluompheny1)-7-dialkylamino-1,8-naphthyridine-3-carboxa mides
• Cholesterol-lowering drug
• NC-1

The apical sodium dependent bile acid transporter (ASBT) is the main transporter to promote re-absorption of bile acids from the intestinal tract into the enterohepatic circulation. Inhibition of ASBT could increase the excretion of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption. Therefore, ASBT is an attractive target for developing new cholesterol-lowering drugs. In this report, a series of 1-(2,4-bifluoropheny1)-7-dialkylamino-1,8-naphthyridine-3-carboxamides were designed as inhibitors of ASBT. Most of them demonstrated potency against ASBT transport of bile acids. In particular, compound 4a(1) was found to have the best activity, resulting in 80.1% inhibition of ASBT at 10 mu mol/L.

• 出版日期2017-3
• 单位北京协和医学院; 中国医学科学院北京协和医院; 河北省人民医院; 河北医科大学