2. Academic Validation
  3. Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer

Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer

  • Bioorg Med Chem Lett. 2013 Apr 1;23(7):1945-8. doi: 10.1016/j.bmcl.2013.02.056.
Robert H Bradbury 1,  David G Acton,  Nicola L Broadbent,  A Nigel Brooks,  Gregory R Carr,  Glenn Hatter,  Barry R Hayter,  Kathryn J Hill,  Nicholas J Howe,  Rhys D O Jones,  David Jude,  Scott G Lamont,  Sarah A Loddick,  Heather L McFarland,  Zaieda Parveen,  Alfred A Rabow,  Gorkhn Sharma-Singh,  Natalie C Stratton,  Andrew G Thomason,  Dawn Trueman,  Graeme E Walker,  Stuart L Wells,  Joanne Wilson,  J Matthew Wood
Affiliations

Affiliation

  • 1 Oncology iMed, AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK. rob.bradbury@astrazeneca.com
PMID: 23466225 DOI: 10.1016/j.bmcl.2013.02.056
Abstract

Removal of the basic piperazine nitrogen atom, introduction of a solubilising end group and partial reduction of the triazolopyridazine moiety in the previously-described lead Androgen Receptor downregulator 6-[4-(4-cyanobenzyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (1) addressed hERG and physical property issues, and led to clinical candidate 6-(4-{4-[2-(4-acetylpiperazin-1-yl)ethoxy]phenyl}piperidin-1-yl)-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine (12), designated AZD3514, that is being evaluated in a Phase I clinical trial in patients with castrate-resistant prostate Cancer.

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