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

PF-998425 nonsteroidal androgen receptor antagonist androgen receptor phototoxicity dermatological use

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 cited in this study

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

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

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

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

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

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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.

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

17 citations, August 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

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Antiandrogens like flutamide are effective in treating conditions like prostate cancer and hair loss, but there's a need for more potent versions. Understanding their structure can help develop better treatments.

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research Treatment of Androgenic Disorders in Women: Acne, Hirsutism, and Alopecia

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Androgen excess disorders in women were effectively treated with spironolactone, estrogen, and dexamethasone.

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