Flutamide analogue

Suggest how the flutamide analogue R3 might disrupt the conformation of the AR. The active enantiomer of R3 is shown. What is its absolute conformation ... 

Prostatic cancer is androgen-dependent and metastatic disease can be helped by orchidectomy, or by a gonadorelin analogue, e.g. buserelin, goserelin, leuprorelin or triptorelin. These cause a transient stimulation of luteinising hormone and thus testosterone release, before inhibition occurs some patients may experience exacerbation of tumour effects, e.g. bone pain, spinal cord compression. Where this can be anticipated, prior orchidectomy or antiandrogen treatment, e.g. with cyproterone or flutamide, is protective. 

Scheflhammer P, Sharifi R, Block N, et al. A controlled trial of bicalu-tamide versus flutamide, each in combination with luteinizing hormonereleasing hormone analogue therapy, in patients with advanced prostate carcinoma Analysis of time to progression. Cancer 1996 78 2164-2169. 

Wen B, Coe KJ, Rademacher P, Fitch WL, Monshouwer M, Nelson SD. Comparison of in vitro bioactivation of flutamide and its cyano analogue Evidence for reductive activation by human NADPH cytochrome P450 reductase. Chem Res Toxicol 2008 Epub. 21(12) 2393-2406. 

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