title: Synthesis and Biological Evaluation of Cyclopentaquinoline Derivatives as Nonsteroidal Glucocorticoid Receptor Antagonists.
abstract: The steroidal glucocorticoid antagonist mifepristone has been reported to improve the symptoms of depression. We report the discovery of 6-(3,5-dimethylisoxazol-4-yl)-2,2,4,4-tetramethyl-2,3,4,7,8,9-hexahydro-1H-cyclopenta[h]quinolin-3-one 3d (QCA-1093) as a novel nonsteroidal glucocorticoid receptor antagonist. The compound displayed potent in vitro activity, high selectivity over other steroid hormone receptors, and significant antidepressant-like activity in vivo.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Eda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kuroda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Aoki
authors.forename: Masami
authors.initials: M
authors.lastname: Yamashita
authors.forename: Chieko
authors.initials: C
authors.lastname: Okumura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohbora
authors.forename: Masaki
authors.initials: M
authors.lastname: Sakaue
authors.forename: Natsumi
authors.initials: N
authors.lastname: Koyama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Aritomo
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D003863:Depression / Q000188:drug therapy*; D006801:Humans; D008297:Male; D062105:Molecular Docking Simulation; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D011804:Quinolines; D011965:Receptors, Glucocorticoid