Glaucoma is a debilitating eye disease that is a leading cause of irreversible blindness. Elevated intraocular pressure (IOP), leading to optic nerve degeneration and visual field loss, is the major contributing attribute associated with the progressive visual field loss that occurs in this disease. Rhopressa® and Rocklatan® have been approved for treatment of primary open-angle glaucoma or ocular hypertension. Netarsudil, the active component in Rhopressa® and Rocklatan® lowers IOP by increasing aqueous humor outflow of the trabecular meshwork through inhibition of Rho Kinase (ROCKi). It also reduces episcleral venous pressure (EVP) to induce additional IOP lowering. As a fixed-dose combination, Rocklatan® also contains latanoprost which lowers IOP by increasing aqueous humor outflow through the uveoscleral pathway. Herein is described syntheses of covalently linked prostaglandins with Netarsudil M-1, creating a single molecule. Upon either topical administration or introduction into a biocompatible and biodegradable implant, these compounds are designed to metabolize to their independent entities and induce aqueous humor outflow greater than Netarsudil or a prostaglandin exhibits individually, resulting in consistently lowered IOP levels.

Covalently linked prostaglandin-ROCK Inhibitors: A new combination strategy for the treatment of glaucoma

ACS Fall 2021

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