Design, Synthesis and Biological Activity of Rigid Cannabinoid CB1 Receptor Antagonists
| Autor: | Axel Stoit, Jos Hubertus Maria Lange, Dijksman Jessica A R, Koos Tipker, Herman H. van Stuivenberg, Chris G. Kruse, Henri C. Wals, Arnold P. den Hartog, Eric Ronken |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
chemistry.chemical_classification
Cannabinoid receptor Cannabinoids Stereochemistry Receptors Drug medicine.medical_treatment Nitro compound Regioselectivity Biological activity General Chemistry General Medicine Electrophilic aromatic substitution Pyrazole Ring (chemistry) Chemical synthesis Rats Adduct chemistry.chemical_compound chemistry Drug Design Drug Discovery medicine Animals Cannabinoid Receptors Cannabinoid |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 50:1109-1113 |
| ISSN: | 1347-5223 0009-2363 |
| Popis: | The design, synthesis and biological activities of potent pyrazole-based tricyclic CB1 receptor antagonists (2) are described. The key synthetic step involves the ring closure of the lithiated alpha, gamma-keto ester adduct (4). The optimal nitroderivative (28) in this series exhibits a high CB1 receptor affinity (pKi=7.2) as well as very potent antagonistic activity (pA2=8.8) in vitro. The regioselectivity of the pyrazole ring closure is shown to depend strongly on the aromatic substitution pattern of the applied arylhydrazine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|