| Literature DB >> 23466225 |
Robert H Bradbury1, 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.
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.Entities:
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Year: 2013 PMID： 23466225 DOI： 10.1016/j.bmcl.2013.02.056
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823