| Literature DB >> 25589936 |
Bryce A Harrison1, Zheng Y Almstead1, Hugh Burgoon1, Michael Gardyan1, Nicole C Goodwin1, Jason Healy1, Ying Liu1, Ross Mabon1, Brett Marinelli1, Lakshman Samala1, Yulian Zhang1, Terry R Stouch1, N Andrew Whitlock2, Suma Gopinathan2, Beth McKnight2, Shuli Wang2, Nita Patel2, Alan G E Wilson2, Brian D Hamman2, Dennis S Rice2, David B Rawlins1.
Abstract
The structure of LX7101, a dual LIM-kinase and ROCK inhibitor for the treatment of ocular hypertension and associated glaucoma, is disclosed. Previously reported LIM kinase inhibitors suffered from poor aqueous stability due to solvolysis of the central urea. Replacement of the urea with a hindered amide resulted in aqueous stable compounds, and addition of solubilizing groups resulted in a set of compounds with good properties for topical dosing in the eye and good efficacy in a mouse model of ocular hypertension. LX7101 was selected as a clinical candidate from this group based on superior efficacy in lowering intraocular pressure and a good safety profile. LX7101 completed IND enabling studies and was tested in a Phase 1 clinical trial in glaucoma patients, where it showed efficacy in lowering intraocular pressure.Entities:
Keywords: LIM-kinase; LX7101; ROCK inhibitor; glaucoma; kinase
Year: 2014 PMID： 25589936 PMCID： PMC4291717 DOI： 10.1021/ml500367g
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345