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.