title: Rational design of a topical androgen receptor antagonist for the suppression of sebum production with properties suitable for follicular delivery.
abstract: A novel nonsteroidal androgen receptor antagonist, (R)-4-(1-benzyl-4,4-dimethyl-2-oxopyrrolidin-3-yloxy)-2-(trifluoromethyl)benzonitrile (1), for the topical control of sebum production is reported. This compound, which is potent, selective, and efficacious in the clinically validated golden Syrian hamster ear animal model, was designed to be delivered to the pilosebaceous unit, the site of action, preferentially by the follicular route.
authors.affiliation: Department of Chemistry, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. lorna.h.mitchell@gmail.com
authors.forename: Lorna H
authors.initials: LH
authors.lastname: Mitchell
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Johnson
authors.forename: Guang Wei
authors.initials: GW
authors.lastname: Lu
authors.forename: Daniel
authors.initials: D
authors.lastname: Du
authors.forename: Kaushik
authors.initials: K
authors.lastname: Datta
authors.forename: Felicity
authors.initials: F
authors.lastname: Grzemski
authors.forename: Veerabahu
authors.initials: V
authors.lastname: Shanmugasundaram
authors.forename: Julie
authors.initials: J
authors.lastname: Spence
authors.forename: Kim
authors.initials: K
authors.lastname: Wade
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Kevin
authors.initials: K
authors.lastname: Sun
authors.forename: Kristin
authors.initials: K
authors.lastname: Lin
authors.forename: Lain-Yen
authors.initials: LY
authors.lastname: Hu
authors.forename: Karen
authors.initials: K
authors.lastname: Sexton
authors.forename: Neil
authors.initials: N
authors.lastname: Raheja
authors.forename: Catherine
authors.initials: C
authors.lastname: Kostlan
authors.forename: David
authors.initials: D
authors.lastname: Pocalyko
mesh_terms: D000287:Administration, Topical; D059002:Androgen Receptor Antagonists; D000818:Animals; D055598:Chemical Phenomena; D006224:Cricetinae; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D018859:Hair Follicle; D006801:Humans; D008297:Male; D008647:Mesocricetus; D009570:Nitriles / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D012629:Sebum / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D059002:Androgen Receptor Antagonists; D009570:Nitriles; C014356:benzonitrile