Novel class of LIM-kinase 2 inhibitors for the treatment of ocular hypertension and associated glaucoma

  • J Med Chem. 2009 Nov 12;52(21):6515-8. doi: 10.1021/jm901226j.
Bryce A Harrison  1 ,  N Andrew Whitlock ,  Michael V Voronkov ,  Zheng Y Almstead ,  Kun-jian Gu ,  Ross Mabon ,  Michael Gardyan ,  Brian D Hamman ,  Jason Allen ,  Suma Gopinathan ,  Beth McKnight ,  Mike Crist ,  Yulian Zhang ,  Ying Liu ,  Lawrence F Courtney ,  Billie Key ,  Julia Zhou ,  Nita Patel ,  Phil W Yates ,  Qingyun Liu ,  Alan G E Wilson ,  S David Kimball ,  Craig E Crosson ,  Dennis S Rice ,  David B Rawlins
Affiliations
  • 1. Department of Medicinal Chemistry, Lexicon Pharmaceuticals, Princeton, New Jersey 08540, USA. [email protected]
PMID: 19831390 DOI: 10.1021/jm901226j
Abstract

The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymatic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of Ocular Hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may be an effective target for treating Ocular Hypertension and associated Glaucoma.

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