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Title: Search for new mGlu7 receptor allosteric modulators with potential activity on the central nervous system
Abstract:
The main aim of the dissertation was to obtain new ligands – negative allosteric modulators (NAMs) of the metabotropic glutamate 7 (mGlu7) receptor subtype. An important aspect of the research was to obtain compounds with high activity and selectivity for the mGlu7 receptor, which at the same time will meet the basic criteria for starting clinical trials, i.e., good solubility, metabolic stability, and safety for patients. The compound library synthesized in this dissertation contained a total of 242 derivatives of eight different chemotypes. All the new compounds were characterized by 1H and 13C NMR and LC‒MS spectra. The quinazolin-4(3H)-one and 1,3-benzothiazole derivatives (eight compounds with an IC50 ≤ 1 µM) showed the highest NAM activity at the mGlu7 receptor. The most active compounds also exhibited high selectivity against the remaining group III receptors and relatively high metabolic stability. Three selected derivatives were tested for their cardiological safety and one for its mutagenic properties. All tested compounds showed no significant activity in the hERG channel blocking assay and in the mini-AMES assay. Initial pharmacological studies were performed to evaluate the therapeutic potential of a few selected quinazolin-4(3H)-one derivative, mGlu7 receptor NAMs, and behavioral tests in mice indicated that the derivatives exhibited ; antipsychotic properties.
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Rada Dyscypliny Nauki farmaceutyczne
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Last modified:
Apr 8, 2024
In our library since:
Apr 8, 2024
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http://dl.cm-uj.krakow.pl:8080/publication/5068
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| Edition name | Date |
|---|---|
| ZB-139414 | Apr 8, 2024 |
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