title: Smoothened antagonists for hair inhibition.
abstract: 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).
authors.affiliation: Department of Chemistry, Michigan Laboratories, Pfizer Global Research & Development, 2800 Plymouth Rd., Ann Arbor, MI 48105, USA. jack.li@bms.com
authors.forename: Jie Jack
authors.initials: JJ
authors.lastname: Li
authors.forename: Veerabahu
authors.initials: V
authors.lastname: Shanmugasundaram
authors.forename: Satya
authors.initials: S
authors.lastname: Reddy
authors.forename: Laura L
authors.initials: LL
authors.lastname: Fleischer
authors.forename: Zenquan
authors.initials: Z
authors.lastname: Wang
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Smith
authors.forename: William G
authors.initials: WG
authors.lastname: Harter
authors.forename: Wen-Song
authors.initials: WS
authors.lastname: Yue
authors.forename: Manju
authors.initials: M
authors.lastname: Swaroop
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Christy Xiaodong
authors.initials: CX
authors.lastname: Ji
authors.forename: Danielle
authors.initials: D
authors.lastname: Dettling
authors.forename: Bella
authors.initials: B
authors.lastname: Osak
authors.forename: Laura R
authors.initials: LR
authors.lastname: Fitzgerald
authors.forename: Robert
authors.initials: R
authors.lastname: Conradi
mesh_terms: 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
chemical_list: D001384:Azetidines; D011720:Pyrazoles; D000518:Eflornithine