Identification of a novel class of androgen receptor antagonists based on the bicyclic-1H-isoindole-1,3(2H)-dione nucleus
| Autor: | Marco M. Gottardis, Aaron Balog, Jieping Geng, Donna D. Wei, Pickering Dacia A, Ricardo M. Attar, Mark E. Salvati, John T. Hunt, Rogelio L. Martinez, Roberto Weinmann, Cheryl A. Rizzo |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Indoles Clinical Biochemistry Mutant Pharmaceutical Science Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship Drug Discovery LNCaP Androgen Receptor Antagonists Tumor Cells Cultured Animals Humans Receptor Molecular Biology Bicyclic molecule Chemistry Organic Chemistry Wild type Antagonist Prostatic Neoplasms Androgen Antagonists Bridged Bicyclo Compounds Heterocyclic Androgen receptor Receptors Androgen Mutation Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 15:389-393 |
| ISSN: | 0960-894X |
| Popis: | A novel series of isoindoledione based compounds were identified as potent antagonists of the androgen receptor (AR). SAR around this series revealed dramatic differences in binding and function in mutant variants (MT) of the AR as compared to the wild type (WT) receptor. Optimization of the aniline portion revealed substitution patterns, which yielded potent antagonist activity against the WT AR as well as the MT AR found in the LNCaP and PCa2b human prostate tumor cell lines. |
| Databáze: | OpenAIRE |
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