Lynestrenol

Clinical data
Trade names	Exluton, Ministat, others
Other names	Linestrenol; Lynenol;[1] NSC-37725; 17α-Ethynylestr-4-en-17β-ol; 19-Nor-17α-pregn-4-en-20-yn-17-ol[1]
AHFS/Drugs.com	International Drug Names
Routes of administration	By mouth
Drug class	Progestogen;Progestin
ATC code	G03AC02 (WHO) G03DC03 (WHO); G03AA03 (WHO)G03AB02 (WHO)G03FA07 (WHO)G03FB02 (WHO) (combinations withestrogens)
Identifiers
IUPAC name (8R,9S,10R,13S,14S,17R)-17-ethynyl-13-methyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol
CAS Number	52-76-6 Y
PubChemCID	5857
ChemSpider	5648 Y
UNII	N2Z8ALG4U5
KEGG	D01580 Y
CompTox Dashboard(EPA)	DTXSID4021478
ECHA InfoCard	100.000.139
Chemical and physical data
Formula	C20H28O
Molar mass	284.443 g·mol−1
3D model (JSmol)	Interactive image
SMILES C#C[C@]2(O)CC[C@H]1[C@H]4[C@H](CC[C@@]12C)[C@@H]3\C(=C/CCC3)CC4
InChI InChI=1S/C20H28O/c1-3-20(21)13-11-18-17-9-8-14-6-4-5-7-15(14)16(17)10-12-19(18,20)2/h1,6,15-18,21H,4-5,7-13H2,2H3/t15-,16+,17+,18-,19-,20-/m0/s1 Y Key:YNVGQYHLRCDXFQ-XGXHKTLJSA-N Y
(verify)

Lynestrenol, sold under the brand namesExluton andMinistat among others, is aprogestin medication which is used inbirth control pills and in the treatment ofgynecological disorders.^[2][3][4] The medication is available both alone and in combination with anestrogen.^[3][5][6] It is takenby mouth.^[7][8]

Lynestrenol is a progestin, or asyntheticprogestogen, and hence is anagonist of theprogesterone receptor, thebiological target of progestogens likeprogesterone.^[9] It has weakandrogenic andestrogenic activity and no other importanthormonal activity.^[9][10] The medication is aprodrug ofnorethisterone in the body, withetynodiol occurring as anintermediate.^[10][11][12]

Lynestrenol was discovered in the late 1950s and was introduced for medical use in 1961.^[13][14] It has mostly been used inEurope and elsewhere in the world and was never marketed in theUnited States.^{[6][15][16][17]}

Lynestrenol is used as a component oforal contraceptives in combination with anestrogen and is used in the treatment ofgynecological disorders such asmenstrual disorders.^[4]

Lynestrenol itself does not bind to theprogesterone receptor and is inactive as aprogestogen.^[7][8] It is aprodrug, and uponoral administration, is rapidly and almost completelyconverted intonorethisterone, a potent progestogen, in theliver duringfirst-pass metabolism.^[7][8] No othermetabolites besides norethisterone are formed from lynestrenol.^[8] As such, itspharmacological activity is essentially identical to that of norethisterone.^[9] The conversion of lynestrenol into norethisterone is catalyzed byCYP2C9 (28.0%),CYP2C19 (49.8%), andCYP3A4 (20.4%), while othercytochrome P450enzymes are each responsible for no more than 1.0% of the total conversion.^[8] It appears that lynestrenol first undergoeshydroxylation of the C3 position, formingetynodiol as anintermediate,^[12] followed byoxygenation of thehydroxyl group to form norethisterone.^[11]

Thepeak blood levels are reached within 2 to 4 hours after oral administration, 97% of the administered dose beingbound to plasma proteins.^{[citation needed]} Lynestrenol and its metabolites are predominantlyexcreted inurine, less infeces,active metabolite norethisteroneelimination half-life being 16 or 17 hours.^{[citation needed]}

Thepharmacokinetics of lynestrenol have been reviewed.^[18]

Lynestrenol, also known as 17α-ethynyl-3-desoxy-19-nortestosterone or as 17α-ethynylestr-4-en-17β-ol, is asyntheticestranesteroid and aderivative of19-nortestosterone.^{[2][3][9][19]} It differs fromnorethisterone (17α-ethynyl-19-nortestosterone) andetynodiol (17α-ethynyl-3-deketo-3β-hydroxy-19-nortestosterone) only by the lack of aketonegroup andhydroxyl group at the C3 position, respectively.^[11]

Chemical syntheses of lynestrenol have been published.^[2][18]

In another approach to analogues,nortestosterone (1) is first converted to the dithioketal (2) by treatment withdithioglycol in the presence ofboron 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 ofJones reagent followed byethynylation of the17-ketone leads to the orally active progestin (6).

Lynestrenol was developed by theDutchpharmaceutical companyOrganon in the late 1950s and was introduced for medical use in 1961.^[13][14] It received a Dutchpatent for lynestrenol in 1957,^[13] and lynestrenol subsequently became a component ofLyndiol, the first Dutch contraceptive pill, in 1962.^[1][13][14] Around this time, pre- and post-marketingclinical trials of lynestrenol were conducted, and in 1965, a study consisting of 200 Dutch women was published.^[13] Lynestrenol was approved, in theUnited Kingdom, in combination withmestranol in 1963 and in combination withethinylestradiol in 1969.^[16]

Lynestrenol is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name,BANTooltip British Approved Name, andJANTooltip Japanese Accepted Name, whilelynestrénol is itsDCFTooltip Dénomination Commune Française andlinestrenolo is itsDCITTooltip Denominazione Comune Italiana.^[2][3][4][6]Lynoestrenol was formerly theBANTooltip British Approved Name of the drug, but it was eventually changed tolynestrenol.^[2][3][4][6]

Lynestrenol has been marketed alone as Exluton, Exlutona, and Orgametril, in combination with mestranol as Anacyclin, Lyndiol, Lyndiol 1, Lyndiol 2.5, Nonovul, and Noracycline, and in combination with ethinylestradiol as Anacyclin, Fysioquens, Minilyn, and Ministat, among other formulations and brand names.^[5][22]

Lynestrenol has been used mainly inEurope^[15] and is also marketed elsewhere throughout the world.^[6] The drug was never marketed in theUnited States.^[16][17]

• Tertiary alcohols
• Ethynyl compounds
• Androgens
• Drugs developed by Schering-Plough
• Drugs developed by Merck & Co.
• Estranes
• Prodrugs
• Progestogens
• Synthetic estrogens

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