1.
Bioorg Med Chem Lett
; 29(2): 342-346, 2019 01 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-30503632
RESUMEN
This letter describes the first account of the chemical optimization (SAR and DMPK profiling) of a new series of mGlu4 positive allosteric modulators (PAMs), leading to the identification of VU0652957 (VU2957, Valiglurax), a compound profiled as a preclinical development candidate. Here, we detail the challenges faced in allosteric modulator programs (e.g., steep SAR, as well as subtle structural changes affecting overall physiochemical/DMPK properties and CNS penetration).