A novel class of apical sodium co-dependent bile acid transporter inhibitors: the 1,2-benzothiazepines.
A series of 5-aryl-3,3-dibutyl-7-(dimethylamino)-1,2-benzothiazepin-4-ol 1,1-dioxides were prepared and were found to inhibit the apical sodium co-dependent bile acid transporter (ASBT) for the potential treatment for hyperlipidemia. Several 1,2-benzothiazepines exhibited low nanomolar in vitro activity. The synthesis and initial in vitro potency data is presented for this novel class of compounds.
Tollefson
Michael B
MB
Pfizer Global Research and Development, 700 Chesterfield Parkway N, Chesterfield, MO 63017, USA. michael.b.tollefson@pfizer.com
Kolodziej
Stephen A
SA
Fletcher
Theresa R
TR
Vernier
William F
WF
Beaudry
Judith A
JA
Keller
Bradley T
BT
Reitz
David B
DB
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004583:Electrons; D006801:Humans; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D029363:Organic Anion Transporters, Sodium-Dependent / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols; D027981:Symporters / Q000037:antagonists & inhibitors*; D013841:Thiazepines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000960:Hypolipidemic Agents; D007202:Indicators and Reagents; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; D013841:Thiazepines; C071908:sodium-bile acid cotransporter; D011092:Polyethylene Glycols