TY  - JOUR
AU  - Ammara, Andrea
AU  - Carone, Alessandra
AU  - Lucarini, Laura
AU  - Sgambellone, Silvia
AU  - Marri, Silvia
AU  - Villano, Serafina
AU  - Matucci, Rosanna
AU  - Luga, Gerta
AU  - Fittipaldi, Chiara
AU  - Pecori, Riccardo
AU  - Pieraccini, Giuseppe
AU  - Di Serio, Claudia
AU  - García-Llorca, Andrea
AU  - Eysteinsson, Thor
AU  - Kalinin, Stanislav
AU  - Viita, Julius Aleksi Olavi
AU  - Urtti, Arto
AU  - Carta, Fabrizio
AU  - Selleri, Silvia
AU  - Supuran, Claudiu T
TI  - Repurposing Drug Metabolites into Dual β-Adrenergic Receptor-Carbonic Anhydrase Modulators as Potential Tools for Ocular Disorders.
JO  - Journal of medicinal chemistry
VL  - nn
SN  - 0095-9065
CY  - Washington, DC
PB  - ACS
M1  - DKFZ-2025-01784
SP  - nn
PY  - 2025
N1  - epub
AB  - 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
LB  - PUB:(DE-HGF)16
C6  - pmid:40857102
DO  - DOI:10.1021/acs.jmedchem.5c01459
UR  - https://inrepo02.dkfz.de/record/304121
ER  -