16-Methylene-17α-hydroxyprogesterone acetate explained

16-Methylene-17α-hydroxyprogesterone acetate is a progestin of the 17α-hydroxyprogesterone group which was never marketed.^{[1] [2] [3] [4] [5]} Given orally, it shows about 2.5-fold the progestogenic activity of parenteral progesterone in animal bioassays. It is a parent compound of the following clinically used progestins:^{[6] [7]}

• Chlormethenmadinone acetate (6-chloro-16-methylene-17α-hydroxy-Δ⁶-progesterone acetate)
• Melengestrol acetate (6-methyl-16-methylene-17α-hydroxy-Δ⁶-progesterone acetate)
• Methenmadinone acetate (16-methylene-17α-hydroxy-Δ⁶-progesterone acetate)
• Segesterone acetate (16-methylene-17α-hydroxy-19-norprogesterone acetate)

Notes and References

1. Kirk DN, Petrow V, Stansfield M, Williamson DM . 481. Modified steroid hormones. Part XIV. 17α-Acetoxy-16-methylenepregn-4-ene-3,20-dione. Journal of the Chemical Society (Resumed) . 1960. 2385–2388. 0368-1769. 10.1039/JR9600002385.
2. Mannhardt HJ, Werder FV, Bork KH, Metz H, Brückner K . Preparation of 16-methylene steroids of the corticoid and progesterone series . Tetrahedron Letters . 16 . 21–32 . 1960 . 1 . 10.1016/S0040-4039(01)99336-0 . 0040-4039.
3. Syhora K . Steroid derivatives. IX. Partial synthesis of 17α-acetoxy-16-methyleneprogesterone . Collection of Czechoslovak Chemical Communications . 26 . 1034–8 . 1961 . 0010-0765 . 10.1135/cccc19611034.
4. Shapiro E, Legatt T, Weber L, Steinberg M, Watnick A, Eisler M, Hennessey MG, Coniglio CT, Charney W, Oliveto EP . 6 . 16-Alkylated Progesterones . Journal of Medicinal and Pharmaceutical Chemistry . 5 . 5 . 975–988 . September 1962 . 14056440 . 10.1021/jm01240a010 .
5. Čekan Z, Šeda M, Mikulášková J, Syhora K . Steroid derivatives XXXIV. On the progestational activity of 6-dehydro-16-methylene-17α-acetoxyprogesterone. Steroids. 4. 3. 1964. 415–421. 0039-128X. 10.1016/0039-128X(64)90154-0.
6. Book: Milne GW . Ashgate Handbook of Endocrine Agents and Steroids. 1 November 2017. Taylor & Francis. 978-1-351-74347-1. 158–162.
7. Book: Denkewalter RG, Tishler M, Ehrhart G, Biel JH, Lum BK, Büchi J, Winter CA, Münzel K, Kunz W, Ariëns EJ, Labhardt F . vanc . Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des recherches pharmaceutiques. 8 March 2013. Birkhäuser. 978-3-0348-7059-7. 407–.