Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer
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- 作者：Robert H. Bradbury ; rob.bradbury@astrazeneca.com ; 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
- 关键词：Prostate cancer ; Androgen receptor downregulator ; AZD3514
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：1 April, 2013
- 年：2013
- 卷：23
- 期：7
- 页码：1945-1948
- 全文大小：445 K
文摘
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.