Rational design of a topical androgen receptor antagonist for the suppression of sebum production with properties suitable for follicular delivery.
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.
Mitchell
Lorna H
LH
Department of Chemistry, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. lorna.h.mitchell@gmail.com
Johnson
Theodore R
TR
Lu
Guang Wei
GW
Du
Daniel
D
Datta
Kaushik
K
Grzemski
Felicity
F
Shanmugasundaram
Veerabahu
V
Spence
Julie
J
Wade
Kim
K
Wang
Zhi
Z
Sun
Kevin
K
Lin
Kristin
K
Hu
Lain-Yen
LY
Sexton
Karen
K
Raheja
Neil
N
Kostlan
Catherine
C
Pocalyko
David
D
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*
D059002:Androgen Receptor Antagonists; D009570:Nitriles; C014356:benzonitrile