Synthesis and characterization of nonsteroidal glucocorticoid receptor modulators for multiple myeloma

  • J Med Chem. 2007 Sep 20;50(19):4699-709. doi: 10.1021/jm070370z.
Andrew R Hudson  1 ,  Steven L Roach ,  Robert I Higuchi ,  Dean P Phillips ,  Reid P Bissonnette ,  William W Lamph ,  Jean Yen ,  Yongkai Li ,  Mark E Adams ,  Lino J Valdez ,  Angie Vassar ,  Catalina Cuervo ,  E Adam Kallel ,  Catherine J Gharbaoui ,  Dale E Mais ,  Jeffrey N Miner ,  Keith B Marschke ,  Deepa Rungta ,  Andrés Negro-Vilar ,  Lin Zhi
Affiliations
  • 1. Discovery Research, Ligand Pharmaceuticals, Inc., 10275 Science Center Drive, San Diego, California 92121, USA. [email protected]
PMID: 17705362 DOI: 10.1021/jm070370z
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.