Atamestane Explained

Atamestane (developmental code name SH-489), also known as metandroden, as well as 1-methylandrosta-1,4-diene-3,17-dione, is a steroidal aromatase inhibitor that was studied in the treatment of cancer.^[1] It blocks the production of estrogen in the body. The drug is selective, competitive, and irreversible in its inhibition of aromatase.^[2]

Synthesis

Reaction of the known compound, androstadienedione, (1) with Gilman reagent followed by acetylation with acetic anhydride gives the enol acetate (2). Bromination with 1,3-dibromo-5,5-dimethylhydantoin gives an intermediate (3) which on treatment with magnesium oxide yields atamestane (4).^[3] Alternatively the steroid (5) can be oxidized with benzeneselenol, or the natural product, boldenone (6) can be oxidized with a mixture of chromium trioxide and sulfuric acid.^[4]

External links

• Atamestane entry in the public domain NCI Dictionary of Cancer Terms

Notes and References

1. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 794–.
2. el Etreby MF . 53256276 . Atamestane: an aromatase inhibitor for the treatment of benign prostatic hyperplasia. A short review . The Journal of Steroid Biochemistry and Molecular Biology . 44 . 4–6 . 565–72 . March 1993 . 7682838 . 10.1016/0960-0760(93)90260-4 .
3. US . 4871482 . Klaus N, Hanfried A . Process for the preparation of 1-methylandrosta-1,4-diene-3,17,dione, and the novel intermediates for this process . patent . 1989-10-03 . 1988-05-06 . Schering AG .
4. 10.1016/S0040-4020(01)89518-1 . Regioselective synthesis of ring a polymethylated steroids in the androstane series . 1989 . Künzer H, Sauer G, Wiechert R . Tetrahedron . 45 . 20 . 6409–6426 .