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

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

Affiliation

  • 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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