Smoothened antagonists for hair inhibition.
A series of aminomethylpyrazoles were prepared and evaluated using cell-based Smoothened beta-lactamase reporter assay and Smoothened binding assay. Potent Smoothened antagonists 10k and 10l were found to inhibit hair growth in vivo in the C3H/HeN mouse hair growth model. The more selective compound 10l was tested negative in the 3T3 NRU assay, indicating a low risk for causing photo-irritation and was efficacious using the C3H/HeN mouse hair growth model although it was slightly less efficacious than that of the reference compound eflornithine (7).
Li
Jie Jack
JJ
Department of Chemistry, Michigan Laboratories, Pfizer Global Research & Development, 2800 Plymouth Rd., Ann Arbor, MI 48105, USA. jack.li@bms.com
Shanmugasundaram
Veerabahu
V
Reddy
Satya
S
Fleischer
Laura L
LL
Wang
Zenquan
Z
Smith
Yvonne
Y
Harter
William G
WG
Yue
Wen-Song
WS
Swaroop
Manju
M
Li
Ling
L
Ji
Christy Xiaodong
CX
Dettling
Danielle
D
Osak
Bella
B
Fitzgerald
Laura R
LR
Conradi
Robert
R
D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000518:Eflornithine / Q000494:pharmacology; D006197:Hair / Q000187:drug effects* / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001384:Azetidines; D011720:Pyrazoles; D000518:Eflornithine