A novel class of apical sodium co-dependent bile acid transporter inhibitors: the 1,2-benzothiazepines

Michael B Tollefson; Stephen A Kolodziej; Theresa R Fletcher; William F Vernier; Judith A Beaudry; Bradley T Keller; David B Reitz

doi:10.1016/j.bmcl.2003.08.004

A novel class of apical sodium co-dependent bile acid transporter inhibitors: the 1,2-benzothiazepines

Bioorg Med Chem Lett. 2003 Nov 3;13(21):3727-30. doi: 10.1016/j.bmcl.2003.08.004.

Authors

Michael B Tollefson¹, Stephen A Kolodziej, Theresa R Fletcher, William F Vernier, Judith A Beaudry, Bradley T Keller, David B Reitz

Affiliation

¹ Pfizer Global Research and Development, 700 Chesterfield Parkway N, Chesterfield, MO 63017, USA. michael.b.tollefson@pfizer.com

PMID: 14552767
DOI: 10.1016/j.bmcl.2003.08.004

Abstract

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.

MeSH terms

Animals
Cell Line
Cricetinae
Electrons
Humans
Hypolipidemic Agents / chemical synthesis*
Hypolipidemic Agents / pharmacology*
Indicators and Reagents
Organic Anion Transporters, Sodium-Dependent / antagonists & inhibitors*
Oxidation-Reduction
Polyethylene Glycols
Symporters / antagonists & inhibitors*
Thiazepines / chemical synthesis*
Thiazepines / pharmacology*

Substances

Hypolipidemic Agents
Indicators and Reagents
Organic Anion Transporters, Sodium-Dependent
Symporters
Thiazepines
sodium-bile acid cotransporter
Polyethylene Glycols