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J Med Chem. 2009 Nov 12;52(21):6515-8. doi: 10.1021/jm901226j.

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

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1
Department of Medicinal Chemistry, Lexicon Pharmaceuticals, Princeton, New Jersey 08540, USA. bharrison@lexpharma.com

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.

PMID:
19831390
DOI:
10.1021/jm901226j
[Indexed for MEDLINE]
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