title: A novel class of apical sodium--dependent bile salt transporter inhibitors: 1-(2,4-bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides.
abstract: 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, compound4a1was found to have the best activity, resulting in 80.1% inhibition of ASBT at 10 μmol/L.
authors.affiliation: Department of Pharmacy, Hebei General Hospital, Shijiazhuang 050051, China; Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Hebei General Hospital, Shijiazhuang 050051, China.
authors.forename: Guoxun
authors.initials: G
authors.lastname: Pang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Ren
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Juxian
authors.initials: J
authors.lastname: Wang
keywords: 1-(2,4-Bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides; ASBT inhibitors; Bile acids; Cholesterol-lowering drug; NC-1