| Autor: |
Prithu Mondal, Dishary Sharmin, Sepideh Rezvanian, Farjana Rashid, Daniel E. Knutson, Lalit K. Golani, Jeffrey M. Witkin, Yeunus Mian, Leggy A. Arnold, Taukir Ahmed, V. V. N. Phani Babu Tiruveedhula, Kamal P. Pandey, Nicolas M Zahn, Zubair Ahmed Khan, James M. Cook |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
ARKIVOC |
| ISSN: |
1551-7012 |
| Popis: |
Antinociceptive ligand HZ-166 is a GABA(A) 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 GABA(A) 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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