%0 Journal Article
%A Ammara, Andrea
%A Carone, Alessandra
%A Lucarini, Laura
%A Sgambellone, Silvia
%A Marri, Silvia
%A Villano, Serafina
%A Matucci, Rosanna
%A Luga, Gerta
%A Fittipaldi, Chiara
%A Pecori, Riccardo
%A Pieraccini, Giuseppe
%A Di Serio, Claudia
%A García-Llorca, Andrea
%A Eysteinsson, Thor
%A Kalinin, Stanislav
%A Viita, Julius Aleksi Olavi
%A Urtti, Arto
%A Carta, Fabrizio
%A Selleri, Silvia
%A Supuran, Claudiu T
%T Repurposing Drug Metabolites into Dual β-Adrenergic Receptor-Carbonic Anhydrase Modulators as Potential Tools for Ocular Disorders.
%J Journal of medicinal chemistry
%V nn
%@ 0095-9065
%C Washington, DC
%I ACS
%M DKFZ-2025-01784
%P nn
%D 2025
%Z epub
%X We report the regioselective chemical derivatization of (R)-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 10-14 and the ureido derivatives 15-18. Such compounds were endowed in vitro with distinct inhibition profiles for the human (h) Carbonic Anhydrases (CAs) and showed preferential agonisms for the β3-AR subtype. Among them, 14 induced remarkable intraocular pressure (IOP) lowering in an in vivo transient model of ocular hypertension, with the maximal effect at 120 min post-administration at 1
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40857102
%R 10.1021/acs.jmedchem.5c01459
%U https://inrepo02.dkfz.de/record/304121