4-(Alkylthio)- and 4-(arylthio)-benzonitrile derivatives as androgen receptor antagonists for the topical suppression of sebum production.
The first examples of thioether-substituted benzonitriles as potential soft-drug androgen receptor antagonists are reported. A number of 4-(alkylthio)- and of 4-(arylthio)-benzonitrile analogs were evaluated in human androgen receptor binding and cellular functional assays. Analogs with potent in vitro binding and cellular activities were evaluated for topical in vivo efficacy in the Golden Syrian hamster ear model. Analogs from both the 4-(alkylthio)- and of 4-(arylthio)-benzonitrile series showed moderate reduction of wax esters in vivo.
Mitchell
Lorna
L
Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, CT13 9QA, UK.
Wang
Zhi
Z
Hu
Lain-Yen
LY
Kostlan
Catherine
C
Carroll
Matthew
M
Dettling
Danielle
D
Du
Daniel
D
Pocalyko
David
D
Wade
Kimberly
K
D000726:Androgen Antagonists / Q000737:chemistry* / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D007313:Insecta; D008297:Male; D008647:Mesocricetus; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011944:Receptors, Androgen / Q000378:metabolism; D012629:Sebum / Q000187:drug effects* / Q000378:metabolism*
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D009570:Nitriles; D011944:Receptors, Androgen; C014356:benzonitrile