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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Harrison BA,Whitlock NA,Voronkov MV,Almstead ZY,Gu KJ,Mabon R,Gardyan M,Hamman BD,Allen J,Gopinathan S,McKnight B,Crist M,Zhang Y,Liu Y,Courtney LF,Key B,Zhou J,Patel N,Yates PW,Liu Q,Wilson AG,Kimball SD,Crosdoi
10.1021/jm901226jsubject
Has Abstractpub_date
2009-11-12 00:00:00pages
6515-8issue
21eissn
0022-2623issn
1520-4804journal_volume
52pub_type
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