Lynestrenol

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Lynestrenol
Lynestrenol.svg
Systematic (IUPAC) name
(17α)-19-Norpregn-4-en-20-yn-17-ol
Clinical data
AHFS/Drugs.com International Drug Names
Identifiers
CAS Number 52-76-6 YesY
ATC code G03AC02 (WHO) G03DC03 (WHO);
G03AA03 (WHO) G03AB02 (WHO) G03FA07 (WHO) G03FB02 (WHO) (combinations with estrogens)
PubChem CID 5857
ChemSpider 5648 YesY
UNII N2Z8ALG4U5 YesY
KEGG D01580 YesY
Chemical data
Formula C20H28O
Molar mass 284.436 g/mol
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Lynestrenol (INN, USAN, BAN, JAN), also known as 17α-ethynyl-3-desoxy-19-nortestosterone or 17α-ethynylestr-4-en-17β-ol, is a steroidal progestin of the 19-nortestosterone group. It is a synthetic, orally active progestogen and has a strong progestogenic effect on the uterine endometrium (transforming proliferative endometrium into secretory one), inhibits secretion of gonadotropins, suppresses maturation of follicles in the ovaries and ovulation, and reduces menstrual bleeding. It is used as an oral contraceptive and in the treatment of gynecological disorders.

Pharmacology[edit]

Lynestrenol itself does not bind to the progesterone receptor and is inactive as a progestogen.[1][2] It is a prodrug, and upon oral administration, is rapidly and almost completely converted into norethisterone, a potent progestogen, in the liver during first-pass metabolism.[1][2] No other metabolites besides norethisterone are formed from lynestrenol.[2] As such, its pharmacological activity is essentially identical to that of norethisterone.[3] The conversion of lynestrenol into norethisterone is catalyzed by CYP2C9 (28.0%), CYP2C19 (49.8%), and CYP3A4 (20.4%), while other cytochrome P450 enzymes are each responsible for no more than 1.0% of the total conversion.[2] It appears that lynestrenol first undergoes hydroxylation of the C3 position followed by oxygenation of the hydroxyl group to form norethisterone.[4]

The peak blood are reached within 2 to 4 hours after oral administration, 97% of the administered dose being bound to plasma proteins.[citation needed] Lynestrenol and its metabolites are predominantly excreted in the urine, less through feces, active metabolite norethisterone elimination half-life being 16 to 17 hours.[citation needed]

Chemistry[edit]

Lynestrenol is a derivative of 19-nortestosterone, and is a member of the estrane subgroup.[3][5] It differs from norethisterone only by the lack of a ketone group at the C3 position.[4]

Synthesis[edit]

In another approach to analogs, nortestosterone (1) is first converted to the dithioketal (2) by treatment with dithioglycol in the presence of boron trifluoride. (The mild conditions of this reaction compared to those usually employed in preparing the oxygen ketals probably accounts for the double bond remaining at 4,5). Treatment of this derivative with sodium in liquid ammonia affords the 3-desoxy analog (3). Oxidation by means of Jones reagent followed by ethynylation of the 17-ketone leads to the orally active progestin (6).

Lynestrenol synthesis:[6][7]

History[edit]

Lynestrenol was introduced in the early 1960s.[8]

References[edit]

  1. ^ a b Odlind V, Weiner E, Victor A, Johansson ED (1979). "Plasma levels of norethindrone after single oral dose administration of norethindrone and lynestrenol". Clin. Endocrinol. (Oxf). 10 (1): 29–38. PMID 436304. 
  2. ^ a b c d Korhonen T, Turpeinen M, Tolonen A, Laine K, Pelkonen O (2008). "Identification of the human cytochrome P450 enzymes involved in the in vitro biotransformation of lynestrenol and norethindrone". J. Steroid Biochem. Mol. Biol. 110 (1-2): 56–66. doi:10.1016/j.jsbmb.2007.09.025. PMID 18356043. 
  3. ^ a b Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (2008). "Classification and pharmacology of progestins". Maturitas. 61 (1-2): 171–80. PMID 19434889. 
  4. ^ a b Stanczyk FZ (2002). "Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception". Rev Endocr Metab Disord. 3 (3): 211–24. PMID 12215716. 
  5. ^ Stanczyk FZ (2003). "All progestins are not created equal". Steroids. 68 (10-13): 879–90. PMID 14667980. 
  6. ^ M. S. de Winter, C. M. Siegmann and S. A. Szpilfogel, Chem. Ind. , 905 (1959).
  7. ^ http://www.chemspider.com/Search.aspx?q=Cingestol
  8. ^ Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments. United Nations Publications. 1983. pp. 134–. ISBN 978-92-1-130230-1.