摘要
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-bifluorophenyl)-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 at10μmol/L.
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-bifluorophenyl)-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 at10μmol/L.
基金
supported by the National Natural Science Foundation of China(Nos.81473098 and 81473099)
Hebei Provincial Key Research Project of Medical Science(Nos.ZD20140027 and 20150588)
