Structure-activity relationships of strychnine analogs at glycine receptors
| Autor: | Ulrike Holzgrabe, Amal M. Y. Mohsen, Anders A. Jensen, Eberhard Heller, Darius P. Zlotos |
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| Rok vydání: | 2014 |
| Předmět: |
Lactams
Stereochemistry Bioengineering General Chemistry General Medicine Strychnine Chemistry Techniques Synthetic Biochemistry chemistry.chemical_compound Inhibitory Concentration 50 Structure-Activity Relationship Receptors Glycine chemistry Lactam Molecular Medicine Potency Moiety Humans Molecular Biology Glycine receptor IC50 |
| Zdroj: | Chemistrybiodiversity. 11(8) |
| ISSN: | 1612-1880 |
| Popis: | Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human α1 and α1β glycine receptors were evaluated. Isostrychnine has shown the best pharmacological profile exhibiting an IC50 value of 1.6 μM at α1 glycine receptors and 3.7-fold preference towards the α1 subtype. SAR Analysis indicates that the lactam moiety and the C(21) = C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine receptors. |
| Databáze: | OpenAIRE |
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