title: Identification of a novel class of androgen receptor antagonists based on the bicyclic-1H-isoindole-1,3(2H)-dione nucleus.
abstract: A novel series of isoindoledione based compounds were identified as potent antagonists of the androgen receptor (AR). SAR around this series revealed dramatic differences in binding and function in mutant variants (MT) of the AR as compared to the wild type (WT) receptor. Optimization of the aniline portion revealed substitution patterns, which yielded potent antagonist activity against the WT AR as well as the MT AR found in the LNCaP and PCa2b human prostate tumor cell lines.
authors.affiliation: Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. mark.salvati@bms.com
authors.forename: Mark E
authors.initials: ME
authors.lastname: Salvati
authors.forename: Aaron
authors.initials: A
authors.lastname: Balog
authors.forename: Donna D
authors.initials: DD
authors.lastname: Wei
authors.forename: Dacia
authors.initials: D
authors.lastname: Pickering
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Attar
authors.forename: Jieping
authors.initials: J
authors.lastname: Geng
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Rizzo
authors.forename: John T
authors.initials: JT
authors.lastname: Hunt
authors.forename: Marco M
authors.initials: MM
authors.lastname: Gottardis
authors.forename: Roberto
authors.initials: R
authors.lastname: Weinmann
authors.forename: Rogelio
authors.initials: R
authors.lastname: Martinez
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D011944:Receptors, Androgen