norprogesterone

19-Norprogesterone
Clinical data
Routes of; administration	Parenteral
Identifiers
	IUPAC name (8R,9S,10R,13S,14S,17S)-17-acetyl-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one;
Synonyms	10-Norprogesterone; 19-Norpregn-4-ene-3,20-dione; 17β-Acetylestr-4-en-3-one
CAS Number	472-54-8;
PubChem CID	228864;
ChemSpider	199224;
Chemical and physical data
Formula	C20H28O2
Molar mass	300.435 g/mol
3D model (JSmol)	Interactive image;
Melting point	144 to 145 °C (291 to 293 °F)
	SMILES O=C4\C=C2/[C@@H]([C@H]1CC[C@@]3([C@@H](C(=O)C)CC[C@H]3[C@@H]1CC2)C)CC4 ;
	InChI InChI=1S/C20H28O2/c1-12(21)18-7-8-19-17-5-3-13-11-14(22)4-6-15(13)16(17)9-10-20(18,19)2/h11,15-19H,3-10H2,1-2H3/t15-,16+,17+,18+,19-,20+/m0/s1 ; Key:NVUUMOOKVFONOM-GPBSYSOESA-N ;

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/07/16 11:45:23」(JST)

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19-Norprogesterone, also known as 19-norpregn-4-ene-3,20-dione, is a steroidal progestin and close analogue of the sex hormone progesterone, lacking only the C19 methyl group of that molecule. It was first synthesized in 1944 in the form of a mixture that also included unnatural stereoisomers (probably C14 (β) and C17 (α)) of progesterone, and this mixture was found to be at least equivalent to progesterone in terms of progestogenic activity.^[1]^[2]^[3]^[4] Subsequent investigations revealed that 17-isoprogesterone and 14-iso-17-isoprogesterone are devoid of progestogenic activity.^[3]^[4] 19-Norprogesterone was resynthesized in 1951 with an improved method,^[3] and was confirmed to be the component of the mixture synthesized in 1944 that was responsible for its progestogenic activity.^[3] In 1953, a paper was published showing that 19-norprogesterone possessed 4- to 8-fold the activity of progesterone in the Clauberg assay in rabbits,^[5] and at the time of this discovery, 19-norprogesterone was the most potent progestogen known.^[6]^[7]

Similarly to progesterone, 19-norprogesterone is a potent progestogen and possesses high affinity for the mineralocorticoid receptor (MR).^[8] However, unlike progesterone, which is an antagonist of the MR, 19-norprogesterone acts as a partial agonist of the MR and produces mineralocorticoid effects such as sodium retention, polydipsia, and hypertension in animals.^[8] Like progesterone, 19-norprogesterone is very active as a progestogen parenterally but is only minimally active orally.^[8] A SAR study found that 19-norprogesterone had 47% of the affinity of aldosterone for the rat MR and that 17α-hydroxylation (17α-hydroxy-19-norprogesterone, or gestronol) decreased it to 13%.^[8] The addition of 6-methylation with formation of a double bond at this position (nomegestrol) further decreased the MR affinity to 1.2% of that of aldosterone, and subsequent acetylation of the 17α-hydroxy group (nomegestrol acetate) nearly abolished it (0.23%).^[8]

The discovery of the retained and potentiated progestogenic activity of 19-norsteroids like 19-norprogesterone resulted in the synthesis of norethisterone, and in turn, the introduction of the first hormonal contraceptives.^[6]^[7] It was reasoned that since ethisterone (17α-ethinyltestosterone) is orally active, and since 19-norprogesterone is a very potent progestin parenterally, that 17α-ethynyl-19-nortestosterone (known now as norethisterone or norethindrone) might be a potent, orally active progestin, and indeed, this was found to be the case.^[6]

19-Norprogesterone is the parent compound of a group of medically used progestins, which includes nomegestrol acetate, promegestone, trimegestone, demegestone, gestonorone caproate, segesterone acetate (nestorone), and norgestomet (veterinary).^[9]^[10]^[11] In addition, the testosterone analogue of 19-norprogesterone, 19-nortestosterone (also known as nandrolone), is an anabolic-androgenic steroid (AAS) and progestogen, and is the parent compound of a large group of AAS and progestins that includes norethisterone.

References

^ Ehrenstein, Maximilian (1944). "INVESTIGATIONS ON STEROIDS. VIII. LOWER HOMOLOGS OF HORMONES OF THE PREGNANE SERIES: 10-NOR-11-DESOXY-CORTICOSTERONE ACETATE AND 10-NORPROGESTERONE1". The Journal of Organic Chemistry. 09 (5): 435–456. ISSN 0022-3263. doi:10.1021/jo01187a009.
^ Allen WM, Ehrenstein M (1944). "10-NOR-PROGESTERONE, A PHYSIOLOGICALLY ACTIVE LOWER HOMOLOG OF PROGESTERONE". Science. 100 (2594): 251–2. PMID 17738394. doi:10.1126/science.100.2594.251.
^ ^a ^b ^c ^d Miramontes, L.; Rosenkranz, G.; Djerassi, Carl (1951). "STEROIDS. XXII. THE SYNTHESIS OF 19-NORPROGESTERONE". Journal of the American Chemical Society. 73 (7): 3540–3541. ISSN 0002-7863. doi:10.1021/ja01151a547.
^ ^a ^b Djerassi, Carl; Miramontes, L.; Rosenkranz, G. (1953). "Steroids. XLVIII.119-Norprogesterone, a Potent Progestational Hormone". Journal of the American Chemical Society. 75 (18): 4440–4442. ISSN 0002-7863. doi:10.1021/ja01114a013.
^ TULLNER WW, HERTZ R (1953). "High progestational activity of 19-norprogesterone". Endocrinology. 52 (3): 359–61. PMID 13033848. doi:10.1210/endo-52-3-359.
^ ^a ^b ^c Enrique Ravina (11 January 2011). The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. pp. 187–. ISBN 978-3-527-32669-3.
^ ^a ^b David A. Williams; William O. Foye; Thomas L. Lemke (January 2002). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 700–. ISBN 978-0-683-30737-5.
^ ^a ^b ^c ^d ^e Paris J, Botella J, Fournau P, Bonnet P, Thevenot R (1987). "Extinction of mineralocorticoid effects in 19-norprogesterone derivatives: structure-activity relationships". J. Pharmacol. Exp. Ther. 243 (1): 288–91. PMID 2822901.
^ Schindler, Adolf E; Campagnoli, Carlo; Druckmann, René; Huber, Johannes; Pasqualini, Jorge R; Schweppe, Karl W; Thijssen, Jos H.H (2003). "Classification and pharmacology of progestins". Maturitas. 46: 7–16. ISSN 0378-5122. PMID 14670641. doi:10.1016/j.maturitas.2003.09.014.
^ Sitruk-Ware, Regine (2004). "Pharmacological profile of progestins". Maturitas. 47 (4): 277–283. ISSN 0378-5122. PMID 15063480. doi:10.1016/j.maturitas.2004.01.001.
^ Sitruk-Ware, R??gine (2004). "New Progestogens". Drugs & Aging. 21 (13): 865–883. ISSN 1170-229X. doi:10.2165/00002512-200421130-00004.

English Journal

Pharmacokinetics, tissue distribution, and excretion of nomegestrol acetate in female rats.

Huang Q1, Chen X2, Zhu Y3, Cao L4, Riviere JE5.
European journal of drug metabolism and pharmacokinetics.Eur J Drug Metab Pharmacokinet.2015 Dec;40(4):435-42. doi: 10.1007/s13318-014-0224-7. Epub 2014 Aug 29.
Nomegestrol acetate (NOMAC), a synthetic progestogen derived from 19-norprogesterone, is an orally active drug with a strong affinity for the progesterone receptor. NOMAC inhibits ovulation and is devoid of undesirable androgenic and estrogenic activities. The aim of this study was to evaluate the p
PMID 25168884

Optimization of the preparation of fluorine-18-labeled steroid receptor ligands 16alpha-[18F]fluoroestradiol (FES), [18F]fluoro furanyl norprogesterone (FFNP), and 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT) as radiopharmaceuticals.

Zhou D1, Lin M, Yasui N, Al-Qahtani MH, Dence CS, Schwarz S, Katzenellenbogen JA.
Journal of labelled compounds & radiopharmaceuticals.J Labelled Comp Radiopharm.2014 May 15;57(5):371-7. doi: 10.1002/jlcr.3191. Epub 2014 Feb 17.
Fluorine-18-labeled steroid receptor tracers, 16α-[(18)F]fluoroestradiol (FES), [(18)F]fluoro furanyl norprogesterone (FFNP), and 16β-[(18)F]fluoro-5α-dihydrotestosterone (FDHT), are important imaging tools for studies of breast and prostate cancers using positron emission tomography (PET). The a
PMID 24861984

Activation of the Pi3k/Akt pathway and modulation of phosphodiesterase activity via membrane progestin receptor-alpha (mPRalpha) regulate progestin-initiated sperm hypermotility in Atlantic croaker.

Tan W1, Thomas P2.
Biology of reproduction.Biol Reprod.2014 May;90(5):105. doi: 10.1095/biolreprod.113.112896. Epub 2014 Apr 2.
Rapid progestin stimulation of sperm motility is a widely observed phenomenon in vertebrates, but the mechanisms governing these effects are still poorly understood, especially in teleosts, amphibians, and birds, which do not express CatSper. Here we show that progestin-stimulated sperm hypermotilit
PMID 24695628

Japanese Journal

Gestenorone capronate(Depostat)による前立腺肥大症の治療

泌尿器科紀要 25(9), p969-976, 1979-09
NAID 120002243710

前立腺肥大症に対する17-hydroxy-19-norprogesterone caproate(SH-582)の効果-2-長期投与症例のその後の経過について (Gestonorone Caproateによる前立腺肥大症の治療-2-<特集>)

泌尿器科紀要 20(11), p707-710, 1974-11
NAID 120002232879

17α-hydroxy-19-norprogesterone caproate使用前後の血中testosteroneの変動について (Gestonorone Caproateによる前立腺肥大症の治療-2-<特集>)

泌尿器科紀要 20(11), p745-747, 1974-11
NAID 120002232874

Related Pictures

[Ehrenstein1944-1] Ehrenstein, Maximilian (1944). "INVESTIGATIONS ON STEROIDS. VIII. LOWER HOMOLOGS OF HORMONES OF THE PREGNANE SERIES: 10-NOR-11-DESOXY-CORTICOSTERONE ACETATE AND 10-NORPROGESTERONE1". The Journal of Organic Chemistry. 09 (5): 435–456. ISSN 0022-3263. doi:10.1021/jo01187a009.

[pmid17738394-2] Allen WM, Ehrenstein M (1944). "10-NOR-PROGESTERONE, A PHYSIOLOGICALLY ACTIVE LOWER HOMOLOG OF PROGESTERONE". Science. 100 (2594): 251–2. PMID 17738394. doi:10.1126/science.100.2594.251.

[MiramontesRosenkranz1951-3] Miramontes, L.; Rosenkranz, G.; Djerassi, Carl (1951). "STEROIDS. XXII. THE SYNTHESIS OF 19-NORPROGESTERONE". Journal of the American Chemical Society. 73 (7): 3540–3541. ISSN 0002-7863. doi:10.1021/ja01151a547.

[DjerassiMiramontes1953-4] Djerassi, Carl; Miramontes, L.; Rosenkranz, G. (1953). "Steroids. XLVIII.119-Norprogesterone, a Potent Progestational Hormone". Journal of the American Chemical Society. 75 (18): 4440–4442. ISSN 0002-7863. doi:10.1021/ja01114a013.

[pmid13033848-5] TULLNER WW, HERTZ R (1953). "High progestational activity of 19-norprogesterone". Endocrinology. 52 (3): 359–61. PMID 13033848. doi:10.1210/endo-52-3-359.

[Ravina2011-6] Enrique Ravina (11 January 2011). The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. pp. 187–. ISBN 978-3-527-32669-3.

[WilliamsFoye2002-7] David A. Williams; William O. Foye; Thomas L. Lemke (January 2002). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 700–. ISBN 978-0-683-30737-5.

[pmid2822901-8] Paris J, Botella J, Fournau P, Bonnet P, Thevenot R (1987). "Extinction of mineralocorticoid effects in 19-norprogesterone derivatives: structure-activity relationships". J. Pharmacol. Exp. Ther. 243 (1): 288–91. PMID 2822901.

[SchindlerCampagnoli2003-9] Schindler, Adolf E; Campagnoli, Carlo; Druckmann, René; Huber, Johannes; Pasqualini, Jorge R; Schweppe, Karl W; Thijssen, Jos H.H (2003). "Classification and pharmacology of progestins". Maturitas. 46: 7–16. ISSN 0378-5122. PMID 14670641. doi:10.1016/j.maturitas.2003.09.014.

[Sitruk-Ware2004a-10] Sitruk-Ware, Regine (2004). "Pharmacological profile of progestins". Maturitas. 47 (4): 277–283. ISSN 0378-5122. PMID 15063480. doi:10.1016/j.maturitas.2004.01.001.

[Sitruk-Ware2004b-11] Sitruk-Ware, R??gine (2004). "New Progestogens". Drugs & Aging. 21 (13): 865–883. ISSN 1170-229X. doi:10.2165/00002512-200421130-00004.

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