Azastene Explained

Azastene (INN, USAN) (developmental code name WIN-17625) is a steroidogenesis inhibitor described as a contraceptive, luteolytic, and abortifacient which was never marketed.^{[1] [2]} It acts as a competitive inhibitor of 3β-hydroxysteroid dehydrogenase (IC₅₀ = 1 μM), and thereby inhibiting the formation of progesterone, corticosteroids, androgens, and estrogens.^{[3] [4]} Due to inhibition of corticosteroid synthesis, azastene is immunosuppressive.

Synthesis

One synthesis of this compound involves initial alkylation of methyl testosterone by means of strong base and methyl iodide to afford the 4,4-dimethyl derivative. Formylation with alkoxide and methyl formate leads to the 2-hydroxymethyl derivative. Reaction of this last with hydroxylamine leads to formation of an isoxazole ring. There is then obtained azastene.

See also

• Cyanoketone

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. 113–.
2. Book: Milne GW . Drugs: Synonyms and Properties: Synonyms and Properties. 8 May 2018. Taylor & Francis. 978-1-351-78989-9. 1457–.
3. Book: Runnebaum B, Rabe T, Kiesel L . Future Aspects in Contraception: Proceeding of an International Symposium held in Heidelberg, 5–8 September 1984 Part 1 Male Contraception. 6 December 2012. Springer Science & Business Media. 978-94-009-4910-2. 74–.
4. Singh H, Jindal DP, Yadav MR, Kumar M . Heterosteroids and drug research . Progress in Medicinal Chemistry . 28 . 233–300 . 1991 . 1843548 . 10.1016/s0079-6468(08)70366-7 . 978-0-08-086276-7 .