Design and Synthesis of New Quinazolin-4-one Derivatives with Negative mGlu₇ Receptor Modulation Activity and Antipsychotic-Like Properties.

ABSTRACT: Following the glutamatergic theory of schizophrenia and based on our previous study regarding the antipsychotic-like activity of mGlu₇ NAMs, we synthesized a new compound library containing 103 members, which were examined for NAM mGlu₇ activity in the T-REx 293 cell line expressing a recombinant human mGlu₇ receptor. Out of the twenty-two scaffolds examined, active compounds were found only within the quinazolinone chemotype. 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171, mGlu₇ IC₅₀ = 6.14 µM) was selective over other group III mGlu receptors (mGlu₄ and mGlu₈), exhibited satisfactory drug-like properties in preliminary DMPK profiling, and was further t

SUBMITTER: Kaczorowska K 

PROVIDER: S-EPMC9916658 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature