Rational Design and Synthesis of 4-((1R,2R)-2-Hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a Novel, Nonsteroidal Androgen Receptor Antagonist Devoid of Phototoxicity for Dermatological Indications

October 2008 in “ Journal of medicinal chemistry ”

Jie Jack Li, Donna M. Iula, Maria Nguyen, Lufei Hu, Danielle Dettling, Theodore R. Johnson, Daniel Du, Veerabahu Shanmugasundaram, Jennifer A. Van Camp, Zhi Wang, William G. Harter, Wen-Song Yue, Mark L. Boys, Kimberly Wade, Elena Drummond, Brian Samas, Bruce A. Lefker, Garrett Hoge, Michael Lovdahl, Jeffrey Asbill, Matthew Carroll, Mary Ann Meade, Susan Ciotti, Theresa Krieger-Burke

TLDR PF-998425 is a new, effective, and non-phototoxic treatment for skin conditions related to androgens.

The document detailed the rational design and synthesis of PF-998425, a novel, nonsteroidal androgen receptor antagonist intended for dermatological use. The compound was specifically engineered to avoid phototoxicity, a common issue with similar treatments. The research involved multiple departments, including Chemistry, Dermatology Biology, Pharmaceutical Sciences, Pharmacokinetics and Drug Metabolism, and Drug Safety, all within Pfizer Global Research & Development. The study highlighted the collaborative effort across various specialized fields to develop a safer and effective treatment for conditions requiring androgen receptor antagonists.

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research (1R,2S)-4-(2-Cyano-Cyclohexyl-Oxy)-2-Trifluoromethyl-Benzonitrile, A Potent Androgen Receptor Antagonist For Stimulating Hair Growth And Reducing Sebum Production

14 citations , November 2007 in “Bioorganic & Medicinal Chemistry Letters”

The compound (1R,2S)-4-(2-Cyano-cyclohexyl-oxy)-2-trifluoromethyl-benzonitrile can stimulate hair growth and reduce oil production when applied topically.

research Preparation of 4-Aryl-2-Trifluoromethylbenzonitrile Derivatives as Androgen Receptor Antagonists for Topical Suppression of Sebum Production

11 citations , October 2007 in “Bioorganic & Medicinal Chemistry Letters”

Scientists made a chemical (compound 4e) that can be applied on skin to reduce oil production, which can help with acne, but it might cause skin sensitivity to light.

research Synthesis and Biological Evaluation of Amino-Pyridines as Androgen Receptor Antagonists for Stimulating Hair Growth and Reducing Sebum Production

17 citations , October 2007 in “Bioorganic & Medicinal Chemistry Letters”

A compound made by Pfizer can potentially stimulate hair growth and reduce oil production, making it a good candidate for topical use.

research Topical Application of Ketoconazole Stimulates Hair Growth in C3H/HeN Mice

24 citations , April 2005 in “The Journal of Dermatology”

Putting ketoconazole on the skin can help mice grow hair.

research Acne

81 citations , January 2002 in “American journal of clinical dermatology”

Hormonal treatments can help with acne, especially in women, by lowering androgen levels or blocking their effects.