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...

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Published inJournal of medicinal chemistry Vol. 53; no. 11; pp. 4422 - 4427
Main Authors Mitchell, Lorna H, Johnson, Theodore R, Lu, Guang Wei, Du, Daniel, Datta, Kaushik, Grzemski, Felicity, Shanmugasundaram, Veerabahu, Spence, Julie, Wade, Kim, Wang, Zhi, Sun, Kevin, Lin, Kristin, Hu, Lain-Yen, Sexton, Karen, Raheja, Neil, Kostlan, Catherine, Pocalyko, David
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 10.06.2010
Amer Chemical Soc
Subjects
Administration, Topical
Androgen Receptor Antagonists
Animals
Chemical Phenomena
Chemistry, Medicinal
Cricetinae
Drug Design
Drug-Related Side Effects and Adverse Reactions
Hair Follicle
Humans
Life Sciences & Biomedicine
Male
Mesocricetus
Nitriles - administration & dosage
Nitriles - metabolism
Nitriles - pharmacokinetics
Nitriles - pharmacology
Pharmacology & Pharmacy
Science & Technology
Sebum - drug effects
Sebum - metabolism
HAMSTER EAR MODEL
WOMEN
SEBACEOUS GLANDS
IN-VITRO
STIMULATING HAIR-GROWTH
CONTROLLED TRIAL
DRUG-DELIVERY
ACNE
PENETRATION
PILOSEBACEOUS UNITS
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Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-2623
1520-4804
DOI:10.1021/jm9018004