title: Synthesis and biological evaluation of amino-pyridines as androgen receptor antagonists for stimulating hair growth and reducing sebum production.
abstract: A series of amino-pyridines were synthesized and evaluated for androgen antagonist activities. Among these compounds, (R)-(+)-6-[methyl-(1-phenyl-ethyl)-amino]-4-trifluoromethyl-nicotinonitrile was the most active example of this class. This compound displayed potent androgen receptor antagonist activity as well as favorable pharmacokinetic characteristics for a potential topical agent. It also demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model.
authors.affiliation: Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor, MI 48105, USA. lain-yen.hu@pfizer.com
authors.forename: Lain-Yen
authors.initials: LY
authors.lastname: Hu
authors.forename: Huangshu John
authors.initials: HJ
authors.lastname: Lei
authors.forename: Daniel
authors.initials: D
authors.lastname: Du
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Johnson
authors.forename: Victor
authors.initials: V
authors.lastname: Fedij
authors.forename: Catherine
authors.initials: C
authors.lastname: Kostlan
authors.forename: Wen Song
authors.initials: WS
authors.lastname: Yue
authors.forename: Mark
authors.initials: M
authors.lastname: Lovdahl
authors.forename: Jie Jack
authors.initials: JJ
authors.lastname: Li
authors.forename: Mathew
authors.initials: M
authors.lastname: Carroll
authors.forename: Danielle
authors.initials: D
authors.lastname: Dettling
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Asbill
authors.forename: Conglin
authors.initials: C
authors.lastname: Fan
authors.forename: Kimberly
authors.initials: K
authors.lastname: Wade
authors.forename: David
authors.initials: D
authors.lastname: Pocalyko
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lapham
authors.forename: Radhika
authors.initials: R
authors.lastname: Yalamanchili
authors.forename: Brian
authors.initials: B
authors.lastname: Samas
authors.forename: Derek
authors.initials: D
authors.lastname: Vrieze
authors.forename: Susan
authors.initials: S
authors.lastname: Ciotti
authors.forename: Teresa
authors.initials: T
authors.lastname: Krieger-Burke
authors.forename: Drago
authors.initials: D
authors.lastname: Sliskovic
authors.forename: Howard
authors.initials: H
authors.lastname: Welgus
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006197:Hair / Q000187:drug effects* / Q000254:growth & development*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008958:Models, Molecular; D015394:Molecular Structure; D011944:Receptors, Androgen / Q000378:metabolism; D012629:Sebum / Q000187:drug effects* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000631:Aminopyridines; D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen