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

BA Harrison, NA Whitlock, MV Voronkov… - Journal of medicinal …, 2009 - ACS Publications
BA Harrison, NA Whitlock, MV Voronkov, ZY Almstead, K Gu, R Mabon, M Gardyan…
Journal of medicinal chemistry, 2009ACS Publications
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.
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.
ACS Publications