biostudies-literatureUnknown68(17)Ammara AWe report the regioselective chemical derivatization of (<i>R</i>)-2-((4-aminophenethyl)amino)-1-phenylethan-1-ol, the primary metabolite of the β₃-Adrenergic Receptor (β₃-AR) agonist mirabegron, with prototypical Carbonic Anhydrase Inhibitors (CAIs) to afford the carbamates <b>10-14</b> and the ureido derivatives <b>15-18</b>. Such compounds were endowed <i>in vitro</i> with distinct inhibition profiles for the human (h) Carbonic Anhydrases (CAs) and showed preferential agonisms for the β₃-AR subtype. Among them, <b>14</b> induced remarkable intraocular pressure (IOP) lowering in an <i>in vivo</i> transient model of ocular hypertension, with the maximal effect at 120 min post-administration at 1% w/v concentration. Furthermore, the high stability of the coJournal of medicinal chemistry18579-18596https://www.ebi.ac.uk/biostudies/studies/S-EPMC12434671biostudies-literatureRepurposing Drug Metabolites into Dual β-Adrenergic Receptor-Carbonic Anhydrase Modulators as Potential Tools for Ocular Disorders.PMC12434671Di Serio CCarta FMatucci RViita JAOMarri SSelleri SLucarini LVillano SAmmara ACarone ASgambellone SEysteinsson TKalinin SPieraccini GLuga GFittipaldi CGarcia-Llorca ASupuran CTPecori RUrtti AfalseRepurposing Drug Metabolites into Dual β-Adrenergic Receptor-Carbonic Anhydrase Modulators as Potential Tools for Ocular Disorders.We report the regioselective chemical derivatization of (<i>R</i>)-2-((4-aminophenethyl)amino)-1-phenylethan-1-ol, the primary metabolite of the β₃-Adrenergic Receptor (β₃-AR) agonist mirabegron, with prototypical Carbonic Anhydrase Inhibitors (CAIs) to afford the carbamates <b>10-14</b> and the ureido derivatives <b>15-18</b>. Such compounds were endowed <i>in vitro</i> with distinct inhibition profiles for the human (h) Carbonic Anhydrases (CAs) and showed preferential agonisms for the β₃-AR subtype. Among them, <b>14</b> induced remarkable intraocular pressure (IOP) lowering in an <i>in vivo</i> transient model of ocular hypertension, with the maximal effect at 120 min post-administration at 1% w/v concentration. Furthermore, the high stability of the co2025-01-01T00:00:00Z2025 Sep2026-06-01T15:44:54.044Z2026-04-08T13:48:52.6ZS-EPMC124346714085710210.1021/acs.jmedchem.5c01459