Novel Class of LIM-Kinase 2 Inhibitors for the Treatment of Ocular Hypertension and Associated Glaucoma

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• 作者：Bryce A. Harrison ; 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 ; Yulia
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：November 12, 2009
• 年：2009
• 卷：52
• 期：21
• 页码：6515-6518
• 全文大小：728K
• 年卷期：v.52,no.21(November 12, 2009)
• ISSN：1520-4804

文摘

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.