| Literature DB >> 21782422 |
Robert H Bradbury1, Neil J Hales, Alfred A Rabow, Graeme E Walker, David G Acton, David M Andrews, Peter Ballard, Nigel A N Brooks, Nicola Colclough, Alan Girdwood, Urs J Hancox, Owen Jones, David Jude, Sarah A Loddick, Andrew A Mortlock.
Abstract
Chemical starting points were investigated for downregulation of the androgen receptor as an approach to treatment of advanced prostate cancer. Although prototypic steroidal downregulators such as 6a designed for intramuscular administration showed insufficient cellular potency, a medicinal chemistry program derived from a novel androgen receptor ligand 8a led to 6-[4-(4-cyanobenzyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (10b), for which high plasma levels following oral administration in a preclinical model compensate for moderate cellular potency.Entities:
Mesh：
Substances：
Year: 2011 PMID： 21782422 DOI： 10.1016/j.bmcl.2011.06.122
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823