Discovery of nonsteroidal glucocorticoid receptor ligands based on 6-indole-1,2,3,4-tetrahydroquinolines.
A series of nonsteroidal glucocorticoid receptor (GR) ligands based on a 6-indole-1,2,3,4-tetrahydroquinoline scaffold are reported. Structure-activity relationship (SAR) of the pendent indole group identified compound 20 exhibiting good GR binding affinity (K(i)=1.5nM) and 100- to 1000-fold selectivity over MR, PR, and AR while showing activity in an E-selectin repression assay.
Roach
Steven L
SL
Discovery Research, Ligand Pharmaceuticals, 10275 Science Center Drive, San Diego, CA 92121, USA. sroach@ligand.com
Higuchi
Robert I
RI
Adams
Mark E
ME
Liu
Yan
Y
Karanewsky
Donald S
DS
Marschke
Keith B
KB
Mais
Dale E
DE
Miner
Jeffrey N
JN
Zhi
Lin
L
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D008024:Ligands; D011804:Quinolines; D011965:Receptors, Glucocorticoid