Discovery of potent and selective urea-based ROCK inhibitors and their effects on intraocular pressure in rats

ACS Medicinal Chemistry Letters

Volumn 1, Issue 4, 2010, Pages 175-179

  Yin, Yan ^a   Cameron, Michael D ^a   Lin, Li ^a   Khan, Susan ^a   Schröter, Thomas ^a   Grant, Wayne ^a   Pocas, Jennifer ^a   Chen, Yen Ting ^a   Schürer, Stephan ^b   Pachori, Alok ^a   Lograsso, Philip ^a   Feng, Yangbo ^a  

^a Translational Research Institute   (United States)

^b UNIVERSITY OF MIAMI   (United States)

Author keywords

Glaucoma; IOP; kinase inhibitor; pyrazole; ROCK; urea

Indexed keywords

ANTIGLAUCOMA AGENT; RHO KINASE INHIBITOR; UREA DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CORNEA; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFECT; DRUG PENETRATION; DRUG POTENCY; DRUG SOLUBILITY; GLAUCOMA; IC 50; INTRAOCULAR PRESSURE; MOLECULAR DOCKING; NONHUMAN; PRIORITY JOURNAL; RAT; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

RATTUS; SUS;

EID: 77955369160     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml1000382     Document Type: Article

References (20)

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18. Corneal permeability was tested in a three-chamber dialysis system with porcine cornea acting as the partitions between the chambers. The cornea was orientated so that the exterior surface was facing the central compound compartment. All three chambers contained pH 7.4 buffer, and the central chamber also contained 100 μM compound. Compound levels were determined in the two terminal chambers at 4 h. Values are the means of the two chambers. The glaucoma drug timolol was used as a reference. Concentrations in the buffer chambers at the 4 h time point were 1.6 μM for timolol, 1.1 μM for 1x, 1.5 μM for 1y, and 1.0 μM for 1z.
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