Smoothened antagonists for hair inhibition

  • Bioorg Med Chem Lett. 2010 Aug 15;20(16):4932-5. doi: 10.1016/j.bmcl.2010.06.033.
Jie Jack Li  1 ,  Veerabahu Shanmugasundaram ,  Satya Reddy ,  Laura L Fleischer ,  Zenquan Wang ,  Yvonne Smith ,  William G Harter ,  Wen-Song Yue ,  Manju Swaroop ,  Ling Li ,  Christy Xiaodong Ji ,  Danielle Dettling ,  Bella Osak ,  Laura R Fitzgerald ,  Robert Conradi
Affiliations
  • 1. Department of Chemistry, Michigan Laboratories, Pfizer Global Research & Development, 2800 Plymouth Rd., Ann Arbor, MI 48105, USA. [email protected]
PMID: 20620058 DOI: 10.1016/j.bmcl.2010.06.033
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).