Unknown

Dataset Information

0

Design, synthesis and characterization of novel gamma‑aminobutyric acid type A receptor ligands.


ABSTRACT: Antinociceptive ligand HZ-166 is a GABAA α2/α3 receptor subtype-selective potentiator. It has been shown to exhibit anxiolytic-like effects in rodent and rhesus monkeys, as well as reduced sedative/ataxic liabilities. In order to improve the metabolic stability of HZ-166, the ethyl ester moiety was bioisosterically replaced with 2,4-disubstituted oxazoles and oxazolines. The new analogs of HZ-166 were synthesized, characterized, and evalutated for their biological activity and docked in the human full-length heteromeric α1β3γ2L GABAA receptor subtype CyroEM structure (6HUO). Importantly no sedation nor ataxia was observed on the rotorod for LKG-I-70 (6) or KPP-III-51 (6c) at 100 and 120 mg/kg, respectively. These was also no loss of righting response for either ligand.

SUBMITTER: Pandey KP 

PROVIDER: S-EPMC7909486 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC22306 | biostudies-literature
| S-EPMC6941172 | biostudies-literature
| S-EPMC5034043 | biostudies-literature
| S-EPMC3307276 | biostudies-literature
| S-EPMC3999301 | biostudies-literature
| S-EPMC4933285 | biostudies-literature
| S-EPMC48465 | biostudies-other
| S-EPMC5215686 | biostudies-literature
| S-EPMC2676040 | biostudies-literature
| S-EPMC7462615 | biostudies-literature