title: 2-(2,2,2-Trifluoroethyl)-5,6-dichlorobenzimidazole derivatives as potent androgen receptor antagonists.
abstract: The synthesis and in vivo SAR of N-benzyl, N-aceto, and N-ethylene ether derivatives of 2-(2,2,2-trifluoroethyl)-5,6-dichloro-benzimidazole as novel androgen receptor antagonists are described. SAR studies led to the discovery of 4-bromo-benzyl benzimidazole 17 as a more potent androgen receptor antagonist in the rat prostate (ID(50)=0.13mg/day), compared with bicalutamide (ID(50)=0.23mg/day).
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, LLC, Drug Discovery, 665 Stockton Drive, Exton, PA 19341, USA.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Ng
authors.forename: Jihua
authors.initials: J
authors.lastname: Guan
authors.forename: Vernon C
authors.initials: VC
authors.lastname: Alford
authors.forename: James C
authors.initials: JC
authors.lastname: Lanter
authors.forename: George F
authors.initials: GF
authors.lastname: Allan
authors.forename: Tifanie
authors.initials: T
authors.lastname: Sbriscia
authors.forename: Scott G
authors.initials: SG
authors.lastname: Lundeen
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
mesh_terms: D000478:Alkylation; D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014105:Tosyl Compounds / Q000494:pharmacology
chemical_list: C518726:2-(2,2,2-trifluoroethyl)-5,6-dichlorobenzimidazole; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D001562:Benzimidazoles; D007202:Indicators and Reagents; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide