VU0486321 is a potent mGlu1 PAM with moderate rat PK (CLp = 13.3. mL/mikg,t1/2 = 54 min), good free fraction (human fu = 0.05, rat fu =0.03) and excellent CNS penetration (Kp = 1.02).
VU0486321 is a compound in a class of mGlu1 positive allosteric modulators (PAMs). VU0486321 maintains acceptable mGlu1 PAM potency, DMPK profile, CNS permeability, and mGluR selectivity.
[1] Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 3. Engineering plasma stability by discovery and optimization of isoindolinone analogs
