title: Preparation of 4-aryl-2-trifluoromethylbenzonitrile derivatives as androgen receptor antagonists for topical suppression of sebum production.
abstract: A series of substituted 4-aryl-2-trifluoromethylbenzonitrile analogs were evaluated in the human androgen receptor binding and cellular functional assays. Analogs with sufficient in vitro binding and cellular potency (IC(50)<200 nM) were tested in the progesterone receptor binding assay for selectivity and in the Golden Syrian hamster ear model for in vivo efficacy. Within the series, compound 4 e was identified to be the most active analog in vivo (wax ester inhibition=86%).
authors.affiliation: Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor, MI 48105, USA. jennifer_vancamp@yahoo.com
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Van Camp
authors.forename: Lain-Yen
authors.initials: LY
authors.lastname: Hu
authors.forename: Catherine
authors.initials: C
authors.lastname: Kostlan
authors.forename: Bruce
authors.initials: B
authors.lastname: Lefker
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Lorna
authors.initials: L
authors.lastname: Mitchell
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Wen-Song
authors.initials: WS
authors.lastname: Yue
authors.forename: Matthew
authors.initials: M
authors.lastname: Carroll
authors.forename: Danielle
authors.initials: D
authors.lastname: Dettling
authors.forename: Daniel
authors.initials: D
authors.lastname: Du
authors.forename: David
authors.initials: D
authors.lastname: Pocalyko
authors.forename: Kimberly
authors.initials: K
authors.lastname: Wade
mesh_terms: D059002:Androgen Receptor Antagonists; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008745:Methylation; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism*; D012629:Sebum / Q000187:drug effects* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D059002:Androgen Receptor Antagonists; D009570:Nitriles; D011944:Receptors, Androgen; D005461:Fluorine; C014356:benzonitrile