Novel Carbonic Anhydrase Inhibitors with Dual-Tail Core Sulfonamide Show Potent and Lasting Effects for Glaucoma Therapy

Glaucoma, a leading cause of irreversible vision loss worldwide, is characterized by elevated intraocular pressure (IOP), a well-established risk factor across all its forms. We present the design and synthesis of 39 novel carbonic anhydrase inhibitors by a dual-tailed approach, strategically crafted to interact with distinct hydrophobic and hydrophilic pockets of CA active sites. The series was investigated against the CA isoforms implicated in glaucoma (hCA II, hCA IV, and hCA XII), and the X-ray crystal structures of compounds