Novel Class of LIM-Kinase 2 Inhibitors for the Treatment of Ocular Hypertension and Associated Glaucoma
Journal of Medicinal Chemistry2009Vol. 52(21), pp. 6515–6518
Citations Over TimeTop 10% of 2009 papers
Bryce A. Harrison, N. Andrew Whitlock, Michael Voronkov, Zheng Y. Almstead, Kun-jian Gu, Ross Mabon, Michael Gardyan, Brian D. Hamman, Jason Allen, Suma Gopinathan, Beth McKnight, Mike J. Crist, Yulian Zhang, Ying Liu, Lawrence F. Courtney, Billie Key, Julia Zhou, Nita Patel, Phil W. Yates, Qingyun Liu, Alan Wilson, S. David Kimball, Craig E. Crosson, Dennis S. Rice, David B. Rawlins
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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