Tetrahydroquinoline glucocorticoid receptor agonists: discovery of a 3-hydroxyl for improving receptor selectivity.
We have previously disclosed a series of glucocorticoid receptor (GR) ligands derived from 6-indole-1,2,3,4-tetrahydroquinolines through structure-activity relationship (SAR) of the pendent C6-indole ring. In parallel with this effort, we now report SAR of the tetrahydroquinoline A-ring that identified the importance of a C3 hydroxyl in improving GR selectivity within a series of non-steroidal GR agonists.
Discovery Research, Ligand Pharmaceuticals, 11085 North Torrey Pines Road, Suite 300, La Jolla, CA 92037, USA. sroach@ligand.com
Steven L
SL
Roach
Robert I
RI
Higuchi
Andrew R
AR
Hudson
Mark E
ME
Adams
Peter M
PM
Syka
Dale E
DE
Mais
Jeffrey N
JN
Miner
Keith B
KB
Marschke
Lin
L
Zhi
D004353:Drug Evaluation, Preclinical; D011485:Protein Binding; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D011804:Quinolines; D011965:Receptors, Glucocorticoid; C542964:1,2,3,4-tetrahydroquinoline