Synthesis and SAR of potent LXR agonists containing an indole pharmacophore

David G Washburn; Tram H Hoang; Nino Campobasso; Angela Smallwood; Derek J Parks; Christine L Webb; Kelly A Frank; Melanie Nord; Chaya Duraiswami; Christopher Evans; Michael Jaye; Scott K Thompson

doi:10.1016/j.bmcl.2009.01.004

Synthesis and SAR of potent LXR agonists containing an indole pharmacophore

Bioorg Med Chem Lett. 2009 Feb 15;19(4):1097-100. doi: 10.1016/j.bmcl.2009.01.004. Epub 2009 Jan 9.

Authors

David G Washburn¹, Tram H Hoang, Nino Campobasso, Angela Smallwood, Derek J Parks, Christine L Webb, Kelly A Frank, Melanie Nord, Chaya Duraiswami, Christopher Evans, Michael Jaye, Scott K Thompson

Affiliation

¹ Department of Chemistry, Molecular Discovery Research, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA. dave.g.washburn@gsk.com

PMID: 19167885
DOI: 10.1016/j.bmcl.2009.01.004

Abstract

A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed. Compounds from this series were potent agonists with good rat pharmacokinetic parameters. In addition, the crystal structure of an LXR agonist bound to LXRalpha will be disclosed.

MeSH terms

Administration, Oral
Animals
Cholesterol / analysis
Combinatorial Chemistry Techniques
Crystallography, X-Ray
DNA-Binding Proteins / agonists*
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology*
Liver X Receptors
Macrophages / drug effects
Mice
Molecular Conformation
Molecular Structure
Orphan Nuclear Receptors
Rats
Receptors, Cytoplasmic and Nuclear / agonists*
Structure-Activity Relationship

Substances

DNA-Binding Proteins
Indoles
Liver X Receptors
Nr1h3 protein, mouse
Nr1h3 protein, rat
Orphan Nuclear Receptors
Receptors, Cytoplasmic and Nuclear
Cholesterol