Here's a publication on one of LGND's lead androgen series:
J Med Chem 1998 Feb 12;41(4):623-639
Synthesis and biological activity of a novel series of nonsteroidal,
peripherally selective androgen receptor antagonists derived from
1,2-dihydropyridono[5,6-g]quinolines.
Hamann LG, Higuchi RI, Zhi L, Edwards JP, Wang XN, Marschke KB, Kong JW, Farmer LJ, Jones TK
Department of Medicinal Chemistry, Ligand Pharmaceuticals, Inc., San Diego, California 92121, USA. lhamann@ligand.com
A new nonsteroidal antiandrogenic pharmacophore has been discovered using cell-based cotransfection assays with human
androgen receptor (hAR). This series of AR antagonists is structurally characterized by a linear tricyclic
1,2-dihydropyridono[5,6-g]quinoline core. Analogues inhibit AR-mediated reporter gene expression and bind to AR as
potently as or better than any known AR antagonists. Several analogues also showed excellent in vivo activity in classic rodent
models of AR antagonism, inhibiting growth of rat ventral prostate and seminal vesicles, without accompanying increases in
serum gonadotropin and testosterone levels, as is seen with other AR antagonists. Investigations of structure-activity
relationships surrounding this pharmacophore resulted in molecules with complete specificity for AR, antagonist activity on an
AR mutant commonly observed in prostate cancer patients, and improved in vivo efficacy. Molecules based on this series of
compounds have the potential to provide unique and effective clinical opportunities for treatment of prostate cancer and other
androgen-dependent diseases.
PMID: 9484511, UI: 98145505 |
