title: Synthesis and characterization of nonsteroidal glucocorticoid receptor modulators for multiple myeloma.
abstract: Structure-activity relationship studies centered around 3'-substituted (Z)-5-(2'-(thienylmethylidene))1,2-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5H-chromeno[3,4-f]quinolines are described. A series of highly potent and efficacious selective glucocorticoid receptor modulators were identified with in vitro activity comparable to dexamethasone. In vivo evaluation of these compounds utilizing a 28 day mouse tumor xenograft model demonstrated efficacy equal to dexamethasone in the reduction of tumor volume.
authors: Discovery Research, Ligand Pharmaceuticals, Inc., 10275 Science Center Drive, San Diego, California 92121, USA. ahudson@ligand.com
authors: Andrew R
authors: AR
authors: Hudson
authors: Steven L
authors: SL
authors: Roach
authors: Robert I
authors: RI
authors: Higuchi
authors: Dean P
authors: DP
authors: Phillips
authors: Reid P
authors: RP
authors: Bissonnette
authors: William W
authors: WW
authors: Lamph
authors: Jean
authors: J
authors: Yen
authors: Yongkai
authors: Y
authors: Li
authors: Mark E
authors: ME
authors: Adams
authors: Lino J
authors: LJ
authors: Valdez
authors: Angie
authors: A
authors: Vassar
authors: Catalina
authors: C
authors: Cuervo
authors: E Adam
authors: EA
authors: Kallel
authors: Catherine J
authors: CJ
authors: Gharbaoui
authors: Dale E
authors: DE
authors: Mais
authors: Jeffrey N
authors: JN
authors: Miner
authors: Keith B
authors: KB
authors: Marschke
authors: Deepa
authors: D
authors: Rungta
authors: Andrés
authors: A
authors: Negro-Vilar
authors: Lin
authors: L
authors: Zhi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D051379:Mice; D000451:Mineralocorticoid Receptor Antagonists; D008958:Models, Molecular; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D018161:Receptors, Mineralocorticoid / Q000819:agonists; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D000451:Mineralocorticoid Receptor Antagonists; D011804:Quinolines; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003907:Dexamethasone