Discovery and optimization of novel, non-steroidal glucocorticoid receptor modulators.
A virtual screening approach comprising a 3-D similarity search based on known GR modulators was used to identify a novel series of non-steroidal glucocorticoid receptor (GR) antagonists. Optimization of the initial hit to provide potent compounds which exhibit good selectivity against other steroidal nuclear hormone receptors is described.
Ray
Nicholas C
NC
Argenta Discovery Ltd, 8/9 Spire Green Centre, Flex Meadow, Harlow, Essex, UK. nick.ray@argentadiscovery.com
Clark
Robin D
RD
Clark
David E
DE
Williams
Karen
K
Hickin
H G
HG
Crackett
Peter H
PH
Dyke
Hazel J
HJ
Lockey
Peter M
PM
Wong
Melanie
M
Devos
René
R
White
Anne
A
Belanoff
Joseph K
JK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005938:Glucocorticoids / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid