17α-Methylprogesterone

Chemical compound (8R,9S,10R,13S,14S,17S)-17-acetyl-10,13,17-trimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one Methylprogesterone.svg skin-invert-image 225px Progestin; Progestogen correct CAS 1046-28-2 correct FDA TYW2G0D7NC 101951 92105 17α-MP; 17α-Methylpregn-4-ene-3,20-dione 22 32 2 CC(=O)C1(CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)C)C 1S/C22H32O2/c1-14(23)21(3)11-9-19-17-6-5-15-13-16(24)7-10-20(15,2)18(17)8-12-22(19,21)4/h13,17-19H,5-12H2,1-4H3/t17-,18+,19+,20+,21-,22+/m1/s1 UFIQEZHBGZCWRS-QZKGNRECSA-N 17α-Methylprogesterone (17α-MP), or 17α-methylpregn-4-ene-3,20-dione, is a steroidal progestin related to progesterone that was synthesized and characterized in 1949 but was never marketed. Plattner PA, Heusser H, Herzig PT Über Steroide und Sexualhormone. 159. Mitteilung. Die Synthese von 17-Methyl-progesteron. Helvetica Chimica Acta February 1949 32 1 270–275 10.1002/hlca.19490320138 18115956 Along with ethisterone (1938) and 19-norprogesterone (1951), 17α-MP was one of the earliest derivatives of progesterone to be identified as possessing progestogenic activity. Zderic JA Progestational hormones Florkin M, Stotz ED Comprehensive Biochemistry Amsterdam Elsevier 1963 166–196 http://www.popline.org/node/474612 https://web.archive.org/web/20161009151731/http://www.popline.org/node/474612 9 October 2016 10 3 Similarly to progesterone and derivatives like 17α-hydroxyprogesterone and 19-norprogesterone, 17α-MP was found to possess poor (though not negligible) oral bioavailability, Martini L, Pecile A Hormonal steroids: biochemistry, pharmacology and therapeutics; proceedings https://books.google.com/books?id=BAlrAAAAMAAJ 1965 Academic Press 95 9780124753020 Progesterone is devoid of appreciable oral activity, but, particularly at positions 6 and 17, substituents of metabolic importance are known to impart oral activity to the molecule (Fieser and Fieser, 1959). We wish to report the preparation of 6- and 21 -substituted 17- methylprogesterones, a class of substances which we synthesized after the observation that 17-methylprogesterone (Plattner et al., 1949), contrary to previous reports (Engel, 1951, 1960), was not devoid of oral activity (cf. Table I). but showed improved progestogenic activity relative to progesterone when administered via other routes (e.g., subcutaneous or vaginal). Shipley EG Anti-Gonadotropic Steroids, Inhibition of Ovulation and Mating Dorfman RI Bioassay https://books.google.com/books?id=WS_LBAAAQBAJ&pg=PA260 3 February 2016 Elsevier 978-1-4832-7276-4 260– 17-Methylprogesterone is effective subcutaneously or intravaginally, but is ineffective orally. Tullner WW, Hertz R High progestational activity of 19-norprogesterone Endocrinology 52 3 359–361 March 1953 13033848 10.1210/endo-52-3-359 17-methylprogesterone A has twice the activity of progesterone using the Corner-Allen assay method (Heuser et al., 1950). In addition to its activity as a progestogen, 17α-MP has also been found to possess some antiglucocorticoid activity. Duncan MR, Duncan GR An in vivo study of the action of antiglucocorticoids on thymus weight ratio, antibody titre and the adrenal-pituitary-hypothalamus axis Journal of Steroid Biochemistry 10 3 245–259 March 1979 222960 10.1016/0022-4731(79)90250-4 The observation of two-fold improved potency of 17α-MP relative to progesterone led to renewed interest in 17α-substituted derivatives of progesterone. Applezweig N Steroid Drugs https://books.google.com/books?id=SIhLAAAAYAAJ 1962 Blakiston Division, McGraw-Hill 101–102 In 1950, 17a-methyl-progesterone was shown to have twice the activity of progesterone. This led to a renewed interest in 17-substituted derivatives. [...] Junkmann of Schering, AG., however, was able to show that long chain esters of 17a-hydroxyprogesterones such as the 17a-caproate produced powerful long-acting progestational effect. This compound is marketed in the United States as Delalutin by Squibb, and has been heavily used for the treatment of habitual abortion. Subsequently, a series of events led to the exploitation of 17a-hydroxyprogesterone derivatives as highly effective and orally active progestogens. Groups at Upjohn, Merck & Co., and Syntex independently found means of readily acetylating the 17-hydroxy group. Later, Upjohn announced it found that 17a-acetoxyprogesterone was orally active in humans and subsequently marketed this compound under the name of Prodox. The idea that progesterone could be protected by substitution against metabolic destruction was not exclusive to one group of investigators. [...] Upjohn later brought out the 6a-methyl-17a-acetoxyprogesterone under the name of Provera. This is ten to twenty-five times as active as ethisterone by oral route. Subsequently, hydroxyprogesterone acetate and hydroxyprogesterone caproate were synthesized in 1953 and introduced in 1956 and 1957, respectively, and medroxyprogesterone acetate was discovered in 1957 and introduced in 1959. In addition, though 17α-MP itself was never introduced for medical use, progestogen derivatives of the compound, including medrogestone (1966) and the 19-norprogesterone derivatives demegestone (1974), promegestone (1983), and trimegestone (2001), have been marketed. Revesz C, Chappel CI Biological activity of medrogestone: a new orally active progestin Journal of Reproduction and Fertility 12 3 473–487 December 1966 4288903 10.1530/jrf.0.0120473 The desirability of an orally active progestin which would be free from these objectionable properties led to the synthesis of a series of derivatives of 17-methylprogesterone (Deghenghi & Gaudry, 1961; Deghenghi, Revesz & Gaudry, 1963) and their testing as progestational agents. The biological activity of 6-methyl-6-dehydro-17-methylprogesterone, which appeared to be the most promising member of this series, [...] free Chemistry List of progestogens See also 17α-Bromoprogesterone Ethinylestradiol Methylestradiol Methyltestosterone References Category:Antiglucocorticoids Category:Diketones Category:Pregnanes Category:Progestogens