A novel class of apical sodium-dependent bile acid transporter inhibitors: the amphiphilic 4-oxo-1-phenyl-1,4-dihydroquinoline derivatives.
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.
Research Laboratories, Sankyo Co. Ltd, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. hitosi@shina.sankyo.co.jp
Hitoshi
H
Kurata
Sayaka
S
Suzuki
Yasuo
Y
Ohhata
Takuya
T
Ikeda
Toru
T
Hasegawa
Ken
K
Kitayama
Toshimori
T
Inaba
Keita
K
Kono
Takafumi
T
Kohama
D000818:Animals; D000924:Anticholesteremic Agents / Q000737:chemistry / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D029363:Organic Anion Transporters, Sodium-Dependent / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000924:Anticholesteremic Agents; D029363:Organic Anion Transporters, Sodium-Dependent; D011804:Quinolines; D027981:Symporters; C071908:sodium-bile acid cotransporter; D002784:Cholesterol