RT Journal Article
T1 2-(Fluoromethoxy)-4′-(S-methanesulfonimidoyl)-1,1′-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson’s Disease
A1 García-Cárceles, Javier
A1 Vázquez-Villa, Henar
A1 Brea Floriani, José Manuel
A1 Ladron de Guevara-Miranda, David
A1 Cincilla, Giovanni
A1 Sánchez-Martínez, Melchor
A1 Sánchez-Merino, Anabel
A1 Algar, Sergio
A1 Frailes, María Teresa de los
A1 Roberts, Richard S.
A1 Ballesteros, Juan A.
A1 Rodríguez de Fonseca, Fernando
A1 Benhamú, Bellinda
A1 Loza García, María Isabel
A1 López-Rodríguez, María L.
AB Tolerance development caused by dopamine replacement with l-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors with orthosteric agonists reveal a significant unmet need for safe and effective treatment of Parkinson’s disease. In search for selective modulators of the D1 receptor, the screening of a chemical library and subsequent medicinal chemistry program around an identified hit resulted in new synthetic compound 26 [UCM-1306, 2-(fluoromethoxy)-4′-(S-methanesulfonimidoyl)-1,1′-biphenyl] that increases the dopamine maximal effect in a dose-dependent manner in human and mouse D1 receptors, is inactive in the absence of dopamine, modulates dopamine affinity for the receptor, exhibits subtype selectivity, and displays low binding competition with orthosteric ligands. The new allosteric modulator potentiates cocaine-induced locomotion and enhances l-DOPA recovery of decreased locomotor activity in reserpinized mice after oral administration. The behavior of compound 26 supports the interest of a positive allosteric modulator of the D1 receptor as a promising therapeutic approach for Parkinson’s disease.
PB ACS Publications
SN 0022-2623
YR 2022
FD 2022-08-31
LK https://hdl.handle.net/10347/45418
UL https://hdl.handle.net/10347/45418
LA eng
NO J. Med. Chem. 2022, 65, 18, 12256–12272
DS Minerva
RD 27 abr 2026