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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (22626)	6/23/1998 1:48:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Rick, I think that you are assuming too much (I didn't send any comments to Jill on this nor had Stan mentioned your name or any of the others that you listed). I did know about the Courtney/r. Peter dale connection and they/he/she/it did post on UNVC.

To: scaram(o)uche who wrote (22626)	6/23/1998 1:54:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Rick, Speaking or r. Peter/Courtney, what do you think about using closely related compounds as designer progestins and designer androgens? Here's a recent anti-androgen abstract: 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