A novel class of apical sodium-dependent bile acid transporter inhibitors: the amphiphilic 4-oxo-1-phenyl-1,4-dihydroquinoline derivatives

Hitoshi Kurata; Sayaka Suzuki; Yasuo Ohhata; Takuya Ikeda; Toru Hasegawa; Ken Kitayama; Toshimori Inaba; Keita Kono; Takafumi Kohama

doi:10.1016/j.bmcl.2003.12.063

A novel class of apical sodium-dependent bile acid transporter inhibitors: the amphiphilic 4-oxo-1-phenyl-1,4-dihydroquinoline derivatives

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1183-6. doi: 10.1016/j.bmcl.2003.12.063.

Authors

Hitoshi Kurata¹, Sayaka Suzuki, Yasuo Ohhata, Takuya Ikeda, Toru Hasegawa, Ken Kitayama, Toshimori Inaba, Keita Kono, Takafumi Kohama

Affiliation

¹ Research Laboratories, Sankyo Co. Ltd, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. hitosi@shina.sankyo.co.jp

PMID: 14980661
DOI: 10.1016/j.bmcl.2003.12.063

Abstract

A series of 4-oxo-1-phenyl-1,4-dihydroquinolines possessing a linker and an ammonio moiety were synthesized and found to inhibit the apical sodium-dependent bile acid transporter (ASBT). The potency of ASBT inhibition varied with the position and length of the linking tether. Compound 21e effectively lowered the total serum cholesterol levels in hamsters.

MeSH terms

Animals
Anticholesteremic Agents / chemistry
Anticholesteremic Agents / pharmacology
Cholesterol / blood
Cricetinae
Male
Mesocricetus
Organic Anion Transporters, Sodium-Dependent / antagonists & inhibitors*
Organic Anion Transporters, Sodium-Dependent / metabolism
Quinolines / chemistry*
Quinolines / pharmacology*
Symporters / antagonists & inhibitors*
Symporters / metabolism

Substances

Anticholesteremic Agents
Organic Anion Transporters, Sodium-Dependent
Quinolines
Symporters
sodium-bile acid cotransporter
Cholesterol