title: Synthesis and SAR of potent and selective androgen receptor antagonists: 5,6-Dichloro-benzimidazole derivatives.
abstract: The synthesis and in vivo SAR of 5,6-dichloro-benzimidazole derivatives as novel selective androgen receptor antagonists are described. During screening of 2-alkyl benzimidazoles, it was found that a trifluoromethyl group greatly enhances antagonist activity in the prostate. Benzimidazole 1 is a potent AR antagonist in the rat prostate (ID50 = 0.15 mg/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: Olivia
authors.initials: O
authors.lastname: Linton
authors.forename: Scott G
authors.initials: SG
authors.lastname: Lundeen
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008297:Male; D008970:Molecular Weight; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis; D013450:Sulfones / Q000138:chemical synthesis
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D001562:Benzimidazoles; D007202:Indicators and Reagents; D013440:Sulfides; D013450:Sulfones