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.

View this study on pubs.acs.org →

Discuss this study in the Community →

Research cited in this study

8 / 8 results

(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

14 citations, August 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.

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

11 citations, August 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.

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

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

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.

research Androgen Receptor Antagonists Structure-Activity Relationships

204 citations, February 2000 in “Current Medicinal Chemistry”

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.

research Importance of Sebaceous Glands in Cutaneous Penetration of an Antiandrogen: Target Effect of Liposomes

62 citations, May 1997 in “Journal of Pharmaceutical Sciences”

Sebaceous glands in the skin play a key role in absorbing the antiandrogen drug RU 58841, especially when it's encapsulated in liposomes.

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

19 citations, July 1990 in “Cleveland Clinic journal of medicine”

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

Similar Research

5 / 1000+ results

Rational Design of a Topical Androgen Receptor Antagonist for the Suppression of Sebum Production with Properties Suitable for Follicular Delivery

research Rational Design of a Topical Androgen Receptor Antagonist for the Suppression of Sebum Production with Properties Suitable for Follicular Delivery

11 citations, May 2010 in “Journal of Medicinal Chemistry”

A new compound was created in 2010 that can control oil production when applied to the skin, and its effects are completely reversible after two weeks.

research Recent Discoveries and Developments of Androgen Receptor-Based Therapy for Prostate Cancer

17 citations, January 2015 in “MedChemComm”

New treatments for prostate cancer are less toxic and show promise, but more research is needed to enhance their effectiveness and reduce side effects.

Probing Androgen Receptor Co-Factor Selectivity Profiles: A Chemical Tool to Determine Cross-Talk Between Androgen Receptor and Beta-Catenin In Vivo

research Probing Androgen Receptor Co-Factor Selectivity Profiles: A Chemical Tool to Determine Cross-Talk Between Androgen Receptor and Beta-Catenin In Vivo

1 citations, January 2013 in “MedChemComm”

PF-05314882 selectively activates androgen receptors without much effect on prostate and may help in prostate cancer treatment and hair loss prevention.

research Inhibitory Activities of Puerariae Flos Against Testosterone 5α-Reductase and Its Hair Growth Promotion Activities

34 citations, August 2011 in “Journal of Natural Medicines”

Puerariae Flos extract may help treat hair loss by blocking a hair loss-related enzyme and promoting hair growth.

research JAK Inhibition in the Treatment of Alopecia Areata: A Promising New Dawn?

29 citations, December 2019 in “Expert review of clinical pharmacology”

JAK inhibitors are a promising new treatment for hair loss and nail problems in alopecia areata.

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

Research cited in this study

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

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

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

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

research Acne

research Androgen Receptor Antagonists Structure-Activity Relationships

research Importance of Sebaceous Glands in Cutaneous Penetration of an Antiandrogen: Target Effect of Liposomes

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

Related Community Posts Join

community I can’t believe my eyes, I’m pretty sure those weren’t here

community Is this VIOFAIRY Minoxidil brand good

community How it’s going so far,I’ve been using fin and minox so far for a year this is the results

community 2 years difference, has being on finasteride for a year helped? Second is after

community Dermastamp only with carrier/essential oil blend