title: Discovery and optimization of novel, non-steroidal glucocorticoid receptor modulators.
abstract: 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.
authors.affiliation: Argenta Discovery Ltd, 8/9 Spire Green Centre, Flex Meadow, Harlow, Essex, UK. nick.ray@argentadiscovery.com
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Ray
authors.forename: Robin D
authors.initials: RD
authors.lastname: Clark
authors.forename: David E
authors.initials: DE
authors.lastname: Clark
authors.forename: Karen
authors.initials: K
authors.lastname: Williams
authors.forename: H G
authors.initials: HG
authors.lastname: Hickin
authors.forename: Peter H
authors.initials: PH
authors.lastname: Crackett
authors.forename: Hazel J
authors.initials: HJ
authors.lastname: Dyke
authors.forename: Peter M
authors.initials: PM
authors.lastname: Lockey
authors.forename: Melanie
authors.initials: M
authors.lastname: Wong
authors.forename: René
authors.initials: R
authors.lastname: Devos
authors.forename: Anne
authors.initials: A
authors.lastname: White
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Belanoff
mesh_terms: 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
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid