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Identification and optimization of a novel series of [2.2.1]-oxabicyclo imide-based androgen receptor antagonists
- Source :
- Bioorganic & Medicinal Chemistry Letters. 18:1910-1915
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- A novel series of [2.2.1]-oxabicyclo imide-based compounds were identified as potent antagonists of the androgen receptor. Molecular modeling and iterative drug design were applied to optimize this series. The lead compound [3aS-(3aalpha,4beta,5beta,7beta,7aalpha)]-4-(octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile was shown to have potent in vivo efficacy after oral dosing in the CWR22 human prostate tumor xenograph model.
- Subjects :
- Male
Models, Molecular
Bicalutamide
medicine.drug_class
Stereochemistry
Clinical Biochemistry
Administration, Oral
Pharmaceutical Science
Isoindoles
Pharmacology
Antiandrogen
Biochemistry
Tosyl Compounds
Mice
Structure-Activity Relationship
chemistry.chemical_compound
Prostate cancer
In vivo
Nitriles
Drug Discovery
Androgen Receptor Antagonists
Tumor Cells, Cultured
medicine
Animals
Humans
Anilides
Imide
Molecular Biology
Chromatography, High Pressure Liquid
Mice, Inbred BALB C
Molecular Structure
Organic Chemistry
Prostatic Neoplasms
Androgen Antagonists
Bridged Bicyclo Compounds, Heterocyclic
medicine.disease
Androgen receptor
chemistry
Receptors, Androgen
Drug Design
Molecular Medicine
Lead compound
Protein Binding
medicine.drug
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....d3e99302645740343483e22497c80e8f