SAR studies: designing potent and selective LXR agonists.
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.
Szewczyk
Jason W
JW
Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. jason_szewczyk@merck.com
Huang
Shaei
S
Chin
Jayne
J
Tian
Jenny
J
Mitnaul
Lyndon
L
Rosa
Raymond L
RL
Peterson
Larry
L
Sparrow
Carl P
CP
Adams
Alan D
AD
D000143:Acids / Q000737:chemistry; D000586:Amination; D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood; D003500:Cyclization; D004268:DNA-Binding Proteins / Q000819:agonists*; D015195:Drug Design; D007211:Indoles / Q000737:chemistry; D000071518:Liver X Receptors; D051379:Mice; D015394:Molecular Structure; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013329:Structure-Activity Relationship
D000143:Acids; D000814:Aniline Compounds; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D007211:Indoles; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C023650:aniline