Identification and optimization of a novel series of [2.2.1]-oxabicyclo imide-based androgen receptor antagonists.

Article Details

Citation

Salvati ME, Balog A, Shan W, Rampulla R, Giese S, Mitt T, Furch JA, Vite GD, Attar RM, Jure-Kunkel M, Geng J, Rizzo CA, Gottardis MM, Krystek SR, Gougoutas J, Galella MA, Obermeier M, Fura A, Chandrasena G

Identification and optimization of a novel series of [2.2.1]-oxabicyclo imide-based androgen receptor antagonists.

Bioorg Med Chem Lett. 2008 Mar 15;18(6):1910-5. doi: 10.1016/j.bmcl.2008.02.006. Epub 2008 Feb 8.

PubMed ID
18291644 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
BicalutamideAndrogen receptorIC 50 (nM)173N/AN/ADetails
BicalutamideAndrogen receptorKi (nM)64N/AN/ADetails