SAR studies: designing potent and selective LXR agonists

Jason W Szewczyk; Shaei Huang; Jayne Chin; Jenny Tian; Lyndon Mitnaul; Raymond L Rosa; Larry Peterson; Carl P Sparrow; Alan D Adams

doi:10.1016/j.bmcl.2006.02.050

SAR studies: designing potent and selective LXR agonists

Bioorg Med Chem Lett. 2006 Jun 1;16(11):3055-60. doi: 10.1016/j.bmcl.2006.02.050. Epub 2006 Mar 10.

Authors

Jason W Szewczyk¹, Shaei Huang, Jayne Chin, Jenny Tian, Lyndon Mitnaul, Raymond L Rosa, Larry Peterson, Carl P Sparrow, Alan D Adams

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. jason_szewczyk@merck.com

PMID: 16529931
DOI: 10.1016/j.bmcl.2006.02.050

Abstract

Counterscreening compounds from a Merck PPAR program discovered lead 1, as a nanomolar LXR/PPAR dual agonist. SAR optimization developed a series of heterocyclic LXR agonists having excellent selectivity over all PPAR isoforms and possessing high LXR affinity and strong in vivo potency.

MeSH terms

Acids / chemistry
Amination
Aniline Compounds / chemistry
Animals
Cholesterol, HDL / blood
Cyclization
DNA-Binding Proteins / agonists*
Drug Design*
Indoles / chemistry
Liver X Receptors
Mice
Molecular Structure
Orphan Nuclear Receptors
Receptors, Cytoplasmic and Nuclear / agonists*
Structure-Activity Relationship

Substances

Acids
Aniline Compounds
Cholesterol, HDL
DNA-Binding Proteins
Indoles
Liver X Receptors
Orphan Nuclear Receptors
Receptors, Cytoplasmic and Nuclear
aniline