Synthesis and biological evaluation of amino-pyridines as androgen receptor antagonists for stimulating hair growth and reducing sebum production.
A series of amino-pyridines were synthesized and evaluated for androgen antagonist activities. Among these compounds, (R)-(+)-6-[methyl-(1-phenyl-ethyl)-amino]-4-trifluoromethyl-nicotinonitrile was the most active example of this class. This compound displayed potent androgen receptor antagonist activity as well as favorable pharmacokinetic characteristics for a potential topical agent. It also demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model.
Hu
Lain-Yen
LY
Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor, MI 48105, USA. lain-yen.hu@pfizer.com
Lei
Huangshu John
HJ
Du
Daniel
D
Johnson
Theodore R
TR
Fedij
Victor
V
Kostlan
Catherine
C
Yue
Wen Song
WS
Lovdahl
Mark
M
Li
Jie Jack
JJ
Carroll
Mathew
M
Dettling
Danielle
D
Asbill
Jeffrey
J
Fan
Conglin
C
Wade
Kimberly
K
Pocalyko
David
D
Lapham
Kimberly
K
Yalamanchili
Radhika
R
Samas
Brian
B
Vrieze
Derek
D
Ciotti
Susan
S
Krieger-Burke
Teresa
T
Sliskovic
Drago
D
Welgus
Howard
H
D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006197:Hair / Q000187:drug effects* / Q000254:growth & development*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008958:Models, Molecular; D015394:Molecular Structure; D011944:Receptors, Androgen / Q000378:metabolism; D012629:Sebum / Q000187:drug effects* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000631:Aminopyridines; D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen