Synthesis and biological evaluation of 3-(prop-2-enyl)- and 3-(prop-2-ynyl)pyrrolidine-2,5-dione derivatives as potential aromatase inhibitors
| Autor: | M. Ahmadi, Paul J. Nicholls, H. J. Smith, W L Woo, Kevin J. Barrell |
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| Rok vydání: | 1996 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Models Molecular Aniline Compounds Pyrrolidines biology Stereochemistry Aromatase Inhibitors Pharmaceutical Science Substrate (chemistry) Succinimides Biological activity Chemical synthesis Aminoglutethimide Pyrrolidine chemistry.chemical_compound Enzyme chemistry Enzyme inhibitor Drug Design biology.protein Aromatase Imide |
| Zdroj: | The Journal of pharmacy and pharmacology. 48(2) |
| ISSN: | 0022-3573 |
| Popis: | 3-(4′-Aminophenyl)pyrrolidine-2,5-dione (WSP3), a known reversible inhibitor of P450 aromatase, was modified using molecular graphics and our model of reversible inhibitor and substrate binding to resemble 10β-prop-2-ynylestr-4-ene-3,17-dione (PED), a mechanism-based inactivator of the enzyme. The analogues prepared were 3-substituted 3-(prop-2-enyl) or 3-(prop-2-ynyl) pyrrolidine-2,5-diones and their N-alkyl derivatives. The reported compounds demonstrated no irreversible (time-dependent) inhibition of the human placental P450 aromatase enzyme. However, some reversible activity was seen in several of the 3-(prop-2-ynyl) compounds. |
| Databáze: | OpenAIRE |
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