title: Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer.
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.
authors: Oncology iMed, AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK. rob.bradbury@astrazeneca.com
authors: Robert H
authors: RH
authors: Bradbury
authors: David G
authors: DG
authors: Acton
authors: Nicola L
authors: NL
authors: Broadbent
authors: A Nigel
authors: AN
authors: Brooks
authors: Gregory R
authors: GR
authors: Carr
authors: Glenn
authors: G
authors: Hatter
authors: Barry R
authors: BR
authors: Hayter
authors: Kathryn J
authors: KJ
authors: Hill
authors: Nicholas J
authors: NJ
authors: Howe
authors: Rhys D O
authors: RD
authors: Jones
authors: David
authors: D
authors: Jude
authors: Scott G
authors: SG
authors: Lamont
authors: Sarah A
authors: SA
authors: Loddick
authors: Heather L
authors: HL
authors: McFarland
authors: Zaieda
authors: Z
authors: Parveen
authors: Alfred A
authors: AA
authors: Rabow
authors: Gorkhn
authors: G
authors: Sharma-Singh
authors: Natalie C
authors: NC
authors: Stratton
authors: Andrew G
authors: AG
authors: Thomason
authors: Dawn
authors: D
authors: Trueman
authors: Graeme E
authors: GE
authors: Walker
authors: Stuart L
authors: SL
authors: Wells
authors: Joanne
authors: J
authors: Wilson
authors: J Matthew
authors: JM
authors: Wood
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C583656:AZD3514; D011724:Pyridazines; D011944:Receptors, Androgen; D054852:Small Molecule Libraries