Improved synthesis of EM-1745, preparation of its C17-ketone analogue and comparison of their inhibitory potency on 17β-hydroxysteroid dehydrogenase type 1

  title={Improved synthesis of EM-1745, preparation of its C17-ketone analogue and comparison of their inhibitory potency on 17$\beta$-hydroxysteroid dehydrogenase type 1},
  author={Marie B{\'e}rub{\'e} and Donald Poirier},
  journal={Journal of Enzyme Inhibition and Medicinal Chemistry},
  pages={832 - 843}
Endocrine therapies are widely used for the treatment of estrogen-sensitive diseases. 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is involved in the last step of the biosynthesis of potent estrogen estradiol (E2). This enzyme catalyzes the reduction of the C17-ketosteroid estrone (E1) into the C17β-hydroxy steroid E2 using the cofactor NAD(P)H. The X-ray analysis of E2/adenosine bisubstrate inhibitor EM-1745 proven that this compound interacts with both the substrate- and the cofactor… 
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