| Literature DB >> 27072905 |
Jill M Sturdivant1, Susan M Royalty2, Cheng-Wen Lin2, Lori A Moore2, Jeffrey D Yingling2, Carmen L Laethem2, Bryan Sherman2, Geoffrey R Heintzelman2, Casey C Kopczynski2, Mitchell A deLong2.
Abstract
Inhibition of Rho kinase (ROCK) to improve fluid outflow through the trabecular meshwork and lower intraocular pressure is a strategy for the development of new anti-glaucoma agents. Alpha-aryl-beta-amino isoquinoline analogs were identified as potent ROCK inhibitors. Compounds that provided a longer duration of intraocular pressure reduction in Dutch Belted rabbits also inhibited norepinephrine transporter. Ester 60 improved bioavailability of its parent ROCK inhibitor, 29 (Ki=0.2nM) and demonstrated an effective and sustained IOP reduction for 24h after dosing. From these studies, netarsudil (a.k.a. AR-13324) was discovered and is currently in clinical trials for the treatment of glaucoma and ocular hypertension.Entities:
Keywords: AR-13324; Glaucoma; Intraocular pressure (IOP); Rho kinase (ROCK); Trabecular meshwork
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Year: 2016 PMID： 27072905 DOI： 10.1016/j.bmcl.2016.03.104
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823