1. Academic Validation
  2. 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

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

  • J Med Chem. 2008 Nov 13;51(21):7010-4. doi: 10.1021/jm8009316.
Jie Jack Li 1 Donna M Iula Maria N Nguyen Lain-Yen Hu Danielle Dettling Theodore R Johnson Daniel Y Du Veerabahu Shanmugasundaram Jennifer A Van Camp Zhi Wang William G Harter Wen-Song Yue Mark L Boys Kimberly J Wade Elena M Drummond Brian M Samas Bruce A Lefker Garrett S Hoge Mark J Lovdahl Jeffrey Asbill Matthew Carroll Mary Ann Meade Susan M Ciotti Theresa Krieger-Burke
Affiliations

Affiliation

  • 1 Department of Chemistry, Michigan Laboratories, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. jack.li@bms.com
Abstract

4-((1 R,2 R)-2-Hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile [PF-0998425, (-)- 6a] is a novel, nonsteroidal Androgen Receptor antagonist for sebum control and treatment of androgenetic alopecia. It is potent, selective, and active in vivo. The compound is rapidly metabolized systemically, thereby reducing the risk of unwanted systemic side effects due to its primary pharmacology. (-)- 6a was tested negative in the 3T3 NRU assay, validating our rationale that reduction of conjugation might reduce potential phototoxicity.

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