Norethisterone

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Norethisterone
Norethisterone.svg
Norethindrone ball-and-stick.png
Systematic (IUPAC) name
(17β)-17-ethynyl-17-hydroxyestr-4-en-3-one;
(8R,9S,10R,13S,14S,17S)-17-ethynyl-17-hydroxy-13-methyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
Clinical data
AHFS/Drugs.com International Drug Names
MedlinePlus a604034
Legal status
?
Pharmacokinetic data
Bioavailability 64%
Protein binding >95%
Half-life 7 hours
Identifiers
CAS number 68-22-4 YesY
ATC code G03AC01 G03DC02
PubChem CID 6230
DrugBank DB00717
ChemSpider 5994 YesY
UNII T18F433X4S YesY
KEGG D00182 YesY
ChEBI CHEBI:7627 YesY
ChEMBL CHEMBL1162 YesY
Chemical data
Formula C20H26O2 
Mol. mass 298.419 g/mol
 YesY (what is this?)  (verify)

Norethisterone (or norethindrone) (or 19-nor-17α-ethynyltestosterone) is a molecule used in some combined oral contraceptive pills, progestogen only pills and is also available as a stand-alone drug. It is a progestogen and can be used to treat premenstrual syndrome, painful periods, abnormal heavy bleeding, irregular periods, menopausal syndrome (in combination with oestrogen), or to postpone a period. It is also commonly used to help prevent uterine hemorrhage in complicated non-surgical or pre-surgical gynecologic cases. Norethindrone was the first orally highly active progestin to be synthesized. It was synthesized for the first time by chemists Luis Miramontes, Carl Djerassi, and George Rosenkranz at Syntex in Mexico City in 1951.[1] It was the progestin used in one of the first three oral contraceptives. Its related ester, norethisterone acetate, is used for the same indications.

Synthesis[edit]

Norethindrone synthesis:

Norethindrone, 17α-Ethynyl-19-nortestosterone, is made from Estr-4-ene-3,17-dione, which in turn is synthesized by partial reduction of the aromatic region of the 3-O-methyl ether of estrone with lithium in liquid ammonia, and simultaneously of the keto group at C17 to a hydroxy group, which is then oxidized back to a keto group by chromium trioxide in acetic acid. The congugated C4-C5 olefin and the carbonyl group at C3 is then transformed to dienol ethyl ether using ethyl orthoformate. The obtained product is ethynylated by acetylene in the presence of potassium tert-butoxide. After HCl hydrolysis of the formed O-potassium derivative, during which the enol ether is also hydrolyzed, and the remaining double bond is shifted, the desired norethindrone is obtained.

References[edit]

  1. ^ a b Djerassi, C.; Miramontes, L.; Rosenkranz, G.; Sondheimer, F. (1954). "Steroids. LIV.1Synthesis of 19-Nov-17α-ethynyltestosterone and 19-Nor-17α-methyltestosterone2". Journal of the American Chemical Society 76 (16): 4092. doi:10.1021/ja01645a010.  edit
  2. ^ Ringold, H. J.; Rosenkranz, G.; Sondheimer, F. (1956). "Steroids. LXXX.11-Methyl-19-nortestosterone and 1-Methyl-17α-ethinyl-19-nortestosterone". Journal of the American Chemical Society 78 (11): 2477. doi:10.1021/ja01592a037.  edit
  3. ^ Ueberwasser, H.; Heusler, K.; Kalvoda, J.; Meystre, C.; Wieland, P.; Anner, G.; Wettstein, A. (1963). "19-Norsteroide II. Ein einfaches Herstellungsverfahren f�r 19-Norandrostan-Derivate. �ber Steroide, 193. Mitteilung". Helvetica Chimica Acta 46: 344. doi:10.1002/hlca.19630460135.  edit
  4. ^ Onken, D; Heublein, D (1970). "Ethinylated steroids". Die Pharmazie 25 (1): 3–9. PMID 4914401.  edit