Review of the Synthesis of Timolol Maleate and Brimonidine Tartrate Drug Substances Used for the Treatment of Open-Angle Glaucoma

Open-angle glaucoma (OAG) is a chronic and degenerative disorder that causes optic nerve damage and potential blindness. The objective of this review is to provide a brief overview on OAG, with emphasis on the importance of β-blockers and α2-agonists for eye care. Timolol maleate (1) and brimonidine tartrate (2) are an important β-blocker and α2-agonist, respectively. Both are used in several medications for the treatment of open-angle glaucoma. A literature review of various synthetic approaches for timolol maleate (1), and brimonidine tartrate (2) drug substances is presented. In addition, the reported timolol maleate (1) and brimonidine tartrate (2) synthetic routes were assessed for strengths and weaknesses from a process chemistry perspective. A summary is provided based on drug substance quality, process, safety, and environmental considerations.