3-(3-Aryloxyaryl)imidazo[1,2-a]pyridine sulfones as liver X receptor agonists

Robert R Singhaus; Ronald C Bernotas; Robert Steffan; Edward Matelan; Elaine Quinet; Ponnal Nambi; Irene Feingold; Christine Huselton; Anna Wilhelmsson; Annika Goos-Nilsson; Jay Wrobel

doi:10.1016/j.bmcl.2009.11.098

3-(3-Aryloxyaryl)imidazo[1,2-a]pyridine sulfones as liver X receptor agonists

Bioorg Med Chem Lett. 2010 Jan 15;20(2):521-5. doi: 10.1016/j.bmcl.2009.11.098. Epub 2009 Nov 23.

Authors

Robert R Singhaus¹, Ronald C Bernotas, Robert Steffan, Edward Matelan, Elaine Quinet, Ponnal Nambi, Irene Feingold, Christine Huselton, Anna Wilhelmsson, Annika Goos-Nilsson, Jay Wrobel

Affiliation

¹ Chemical Sciences, Wyeth Pharmaceuticals, 500 Arcola Rd., Collegeville, PA 19426, USA. Singhar@wyeth.com

PMID: 20005711
DOI: 10.1016/j.bmcl.2009.11.098

Abstract

Replacement of a quinoline with an imidazo[1,2-a]pyridine in a series of liver X receptor (LXR) agonists incorporating a [3-(sulfonyl)aryloxyphenyl] side chain provided high affinity LXR ligands 7. In functional assays of LXR activity, good agonist potency and efficacy were found for several analogs.

MeSH terms

ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / metabolism
Animals
Hep G2 Cells
Humans
Liver X Receptors
Mice
Microsomes, Liver / metabolism
Orphan Nuclear Receptors / agonists*
Orphan Nuclear Receptors / metabolism
Protein Binding
Pyridines / chemical synthesis*
Pyridines / chemistry
Pyridines / pharmacology
Quinolines / chemical synthesis*
Quinolines / chemistry
Quinolines / pharmacology
RNA, Messenger / metabolism
Structure-Activity Relationship
Sulfones / chemical synthesis*
Sulfones / chemistry
Sulfones / pharmacology

Substances

ATP-Binding Cassette Transporters
Liver X Receptors
Orphan Nuclear Receptors
Pyridines
Quinolines
RNA, Messenger
Sulfones
pyridine