Water-soluble PDE4 inhibitors for the treatment of dry eye

  • Bioorg Med Chem Lett. 2010 May 1;20(9):2928-32. doi: 10.1016/j.bmcl.2010.03.023.
Steven P Govek  1 ,  Guy Oshiro ,  John V Anzola ,  Clay Beauregard ,  Jasmine Chen ,  Avery R Coyle ,  Daniel A Gamache ,  Mark R Hellberg ,  Jennifer N Hsien ,  Julia M Lerch ,  John C Liao ,  James W Malecha ,  Lena M Staszewski ,  David J Thomas ,  John M Yanni ,  Stewart A Noble ,  Andrew K Shiau
Affiliations
  • 1. Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, United States. [email protected]
PMID: 20378348 DOI: 10.1016/j.bmcl.2010.03.023
Abstract

PDE4 inhibitors have the potential to alleviate the symptoms and underlying inflammation associated with dry eye. Disclosed herein is the development of a novel series of water-soluble PDE4 inhibitors. Our studies led to the discovery of coumarin 18, which is effective in a rabbit model of dry eye and a tear secretion test in rats.