Chemistry:List of estrogen esters
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Estradiol, the base estrogen of most estrogen esters.
This is a list of estrogen esters, or ester prodrugs of estrogens. It includes esters, as well as ethers, of steroidal estrogens like estradiol, estrone, and estriol and of nonsteroidal estrogens like the stilbestrols diethylstilbestrol and hexestrol.
Esters of steroidal estrogens
Estradiol esters
Marketed
Many esters of estradiol have been marketed, including the following major esters:[1][2]
- Estradiol acetate (Femring, Femtrace, Menoring)
- Estradiol benzoate (Agofollin Depot, Progynon-B; Duogynon, Primosiston, Sistocyclin)
- Estradiol cypionate (Depo-Estradiol, Depofemin, Estradep; Cyclofem, Lunelle)
- Estradiol dipropionate (Agofollin, Di-Ovocyclin, Progynon-DP; EP Hormone Depot)
- Estradiol enantate (Perlutal, Topasel, Unalmes, Yectames)
- Estradiol undecylate (Delestrec, Progynon Depot)
- Estradiol valerate (Delestrogen, Progynon Depot, Progynova; Gravibinon, Mesigyna, Mesygest)
- Polyestradiol phosphate (Estradurin) (an estradiol ester in polymeric form)
And the following less commonly used esters:[1][2]
- Cloxestradiol acetate (Genovul; diacetate ester of cloxestradiol, or estradiol 17β-chloral hemiacetal ether)
- Estradiol benzoate butyrate (Redimen, Soluna, Unijab, Unimens)
- Estradiol butyrylacetate (Follikoside)
- Estradiol dibutyrate (Triormon Depositum)
- Estradiol dienantate (Climacteron, Lactimex, Lactostat)
- Estradiol diundecylate (Estrolent; Trioestrine Retard)
- Estradiol diundecylenate (Etrosteron)
- Estradiol furoate (Di-Folliculine)
- Estradiol hemisuccinate (Eutocol; Hosterona)
- Estradiol hemihydrate (Estrofem)
- Estradiol hexahydrobenzoate (Benzo-Ginoestril A.P., BenzoGynoestryl Retard, Ginestryl-15-Depot, Menodin, Tardoginestryl)
- Estradiol palmitate (Esmopal)
- Estradiol phenylpropionate (Dimenformon Prolongatum; Estandron Prolongatum, Lynandron Prolongatum, Mixogen)
- Estradiol pivalate (Estrotate; Estrotate with Progesterone)
- Estradiol propionate (estradiol 17β-propionate) (Acrofollin, Akrofollin, Follhormon)
- Estradiol propoxyphenylpropionate (Durovex)
- Estradiol stearate (Depofollan)
- Estradiol sulfate (a minor constituent of conjugated estrogens (Premarin))
The following nitrogen mustard ester of estradiol is a cytostatic antineoplastic agent and has been marketed:[1][2]
- Estramustine phosphate (Emcyt, Estracyt; estradiol 3-normustine 17β-phosphate)
Never marketed
A number of other estradiol esters which have not been marketed include:[2]
- Estradiol 3-furoate[3]
- Estradiol 3-propionate (not to be confused with estradiol monopropionate (estradiol 17β-propionate))
- Estradiol 17β-(1-(4-(aminosulfonyl)benzoyl)-L-proline) (EC508)[4][5][6][7]
- Estradiol acetate benzoate[8][9]
- Estradiol 17β-acetate
- Estradiol 17β-benzoate
- Estradiol acetylsalicylate (estradiol 3-acetylsalicylate)[10][11]
- Estradiol anthranilate (estradiol 3-anthranilate)[10][11]
- Estradiol arachidonate
- Estradiol benzoate cyclooctenyl ether (estradiol 3-benzoate 17β-cyclooctenyl ether; EBCO)[12][13]
- Estradiol caprylate (estradiol octanoate)[14][15]
- Estradiol cyclooctyl acetate (E2CoA)[16]
- Estradiol decanoate (estradiol 17β-decanoate)[17]
- Estradiol diacetate
- Estradiol dibenzoate
- Estradiol dicypionate
- Estradiol dioleate
- Estradiol dipalmitate
- Estradiol distearate
- Estradiol disulfate
- Estradiol glucuronide
- Estradiol sulfate glucuronide
- Estradiol linoleate
- Estradiol oleate
- Estradiol phosphate
- Estradiol salicylate (estradiol 3-salicylate)[10][11]
- Estradiol sulfamate (E2MATE; J995, PGL-2, PGL-2001, ZK-190628; estradiol-3-O-sulfamate)
- Estradiol undecylenate (SH-368)
- Estrapronicate (estradiol 3-propionate 17β-nicotinate; Trophobolene, Trophoboline)
- Orestrate (estradiol 3-propionate 17β-(1-cyclohexenyl) ether)
The following cytostatic antineoplastic nitrogen mustard esters of estradiol have not been marketed:[2]
- Alestramustine (estradiol 3-(bis(2-chloroethyl)carbamate), 17-ester with L-alanine)
- Atrimustine (KM-2210; bestrabucil, busramustine)
- Estradiol mustard (NSC-112259; chlorphenacyl estradiol diester)
- Estramustine (Leo 275; Ro 21-8837)
- Estromustine (Leo 271 f; estrone 17β-3-N-bis(2-chloroethyl)carbamate, estrone–cytostatic complex)
Estrone esters
Marketed
Esters of estrone that have been marketed include:[1][2]
- Estrone acetate (Hovigal)
- Estrone sulfate (as the primary component of conjugated estrogens (Premarin))
- Estropipate (Ogen, Ortho-Est) (a salt of estrone sulfate and piperazine)
- Estrone tetraacetylglucoside (Glucovex, Glycovex)
Never marketed
Other estrone esters which are notable but have not been marketed include:
- Estrone benzoate
- Estrone cyanate
- Estrone enanthate[18]
- Estrone enanthate benzilic acid hydrazone[18]
- Estrone glucuronide
- Estrone phosphate
- Estrone propionate[19]
- Estrone sulfamate (EMATE; J994; estrone-3-O-sulfamate)
- Estrone oleate
Estriol esters
Marketed
Esters of estriol that have been marketed include:[1][2]
- Estriol 3-glucuronide (as a component of conjugated estriol (Emmenin, Progynon))
- Estriol acetate benzoate (Holin-Depot)
- Estriol glucuronide (as a component of conjugated estriol (Emmenin, Progynon))
- Estriol succinate (Sinapause, Styptanon, Synapause)
- Estriol sodium succinate (Pausan, Styptanon)
- Estriol sulfate (as a component of conjugated estriol (Emmenin, Progynon))
- Estriol sulfate glucuronide (as a component of conjugated estriol (Emmenin, Progynon))
- Estriol tripropionate (Estriel)
- Polyestriol phosphate (Gynäsan, Klimadurin, Triodurin) (an estriol ester in polymeric form)
Never marketed
The following ester of estriol was never marketed:
- Estriol dihexanoate
- Estriol dipropionate
- Estriol phosphate (E3P)
- Estriol sulfamate (E3MATE; J1034; estriol-3-O-sulfamate)
- Estriol triacetate
Ethinylestradiol esters
Marketed
The following esters of ethinylestradiol exist and have been marketed:[1][2]
- Ethinylestradiol sulfonate (Turisteron; ethinylestradiol 3-isopropylsulfonate)
Never marketed
- Ethinylestradiol benzoate – the 3-benzoate ester of ethinylestradiol
- Ethinylestradiol N,N-diethylsulfamate (J271) – the 3-(N,N-diethyl)sulfamate ester of ethinylestradiol[20]
- Ethinylestradiol pyrrolidinosulfonate (J272) – the 3-pyrrolidinosulfonate ester of ethinylestradiol[20]
- Ethinylestradiol sulfamate (J1028) – the 3-sulfamate ester of ethinylestradiol[21]
- Ethinylestradiol sulfate
Esters of other steroidal estrogens
Marketed
The following esters of other estrogens exist and have been marketed:[1]
- Hydroxyestrone diacetate (Colpoginon, Colpormon, Hormobion, Hormocervix) – the 3,16α-diacetate ester of 16α-hydroxyestrone
Ethers of steroidal estrogens
Marketed
A number of estrogen ethers also exist and have been marketed, including:[22][1]
- Clomestrone (Arterolo, Atheran, Colesterel, Iposclerone, Liprotene, Persclerol) – the 3-methyl ether of 16α-chloroestrone
- Cloxestradiol acetate (Genovul) – the O,O-diacetate ester of cloxestradiol (estradiol 17β-chloral hemiacetal ether)
- Mestranol (Devocin, Ovastol, Tranel) (component of Enovid, Enavid, Ortho-Novin, Femigen, Norbiogest) – the 3-methyl ether of ethinylestradiol
- Moxestrol (Surestryl) – the 11β-methoxy derivative of ethinylestradiol (and hence the 11β-methyl ether of the 11β-hydroxyl derivative of ethinylestradiol)
- Nilestriol (Wei Ni An) – the 3-cyclopentyl ether of ethinylestriol
- Promestriene (Colpotrofin, Colpotrophine, Delipoderm) – the 3-propyl and 17β-methyl diether of estradiol
- Quinestradol (Colpovis, Colpovister, Pentovis) – the 3-cyclopentyl ether of estriol
- Quinestrol (Agalacto-Quilea, Basaquines, Eston, Estrovis, Estrovister, Plestrovis, Qui-lea) – the 3-cyclopentyl ether of ethinylestradiol
Never marketed
A few other estrogen ethers which are notable but have not been marketed include:[22]
- Cloxestradiol – the 17β-chloral hemiacetal ether of estradiol
- Estradiol benzoate cyclooctenyl ether – the 17β-cyclooctenyl ether of estradiol 3-benzoate[12]
- Estradiol 3-saccharinylmethyl ether – the 3-(saccharinylmethyl) ether of estradiol[23][24]
- Estradiol 3-tetrahydropyranyl ether – the 3-(tetrahydropyran-2-yl) ether of estradiol[25]
- Estradiol 17β-tetrahydropyranyl ether – the 17β-(tetrahydropyran-2-yl) ether of estradiol[25]
- Estrone methyl ether – the 3-methyl ether of estrone
- Mytatrienediol – the 3-methyl ether of 16α-methyl-16β-epiestriol
- Orestrate – the 17β-(1-cyclohexenyl) ether of estradiol 3-propionate
Esters of nonsteroidal estrogens
Diethylstilbestrol esters
Marketed
Major esters of diethylstilbestrol include:
- Diethylstilbestrol dipropionate (Agostilben, Biokeral, Clinestrol, Cyclen, Estilbin, Estril, Neobenzoestrol, Orestol, Oroestrol, Ostregenin, Prostilbene, Stilbestriol DP, Stilboestrolum Dipropionicum, Stilboestrol, Synestrin, Willestrol)
- Fosfestrol (diethylstilbestrol diphosphate) (Honvan, Difostilben, Fosfostilben, Fostrolin, Stilbol, Stilphostrol, Vagestrol)
Less commonly used esters of diethylstilbestrol include:
- Diethylstilbestrol diacetate (Hormostilboral Stark)
- Diethylstilbestrol dilaurate (Acnestrol-Lotion)
- Diethylstilbestrol dipalmitate (stilpalmitate) (Palmestril, Stilpalmitate)
- Diethylstilbestrol disulfate (Hydroestryl, Idroestril)
Never marketed
- Diethylstilbestrol sulfate
- Furostilbestrol (diethylstilbestrol difuroate)
- Polydiethylstilbestrol phosphate
As well as the following nitrogen mustard ester:
- ICI-85966 (Stilbostat; diethylstilbestrol bis(di(2-chloroethyl)carbamate))
Hexestrol esters
Marketed
- Hexestrol diacetate (Retalon Lingual, Robal, Sintestrol, Sintofolin)
- Hexestrol dicaprylate (dioctanoylhexestrol) (Taston)
- Hexestrol diphosphate (Cytostesin, Pharmestrin, Retalon Aquosum)
- Hexestrol dipropionate (Hexanoestrol, Retalon Oleosum)
- Hexestrol phosphate (Retalon Aquosum)
Never marketed
The following nitrogen mustard ester of hexestrol was never marketed:
- Phenestrol (fenestrol; hexestrol bis[4-[bis(2-chloroethyl)amino]phenylacetate)
Esters of other nonsteroidal estrogens
Marketed
- Dienestrol diacetate (Faragynol, Gynocyrol)
- Methestrol dipropionate (promethestrol dipropionate, dimethylhexestrol dipropionate) (Meprane Dipropionate)
Ethers of nonsteroidal estrogens
Diethylstilbestrol
Marketed
- Diethylstilbestrol monobenzyl ether (benzelstilbestrol) (Monozol, Hypantin, Pituitrope)
- Dimestrol (dianisylhexene, diethylstilbestrol dimethyl ether, dimethoxydiethylstilbestrol) (Depot-Ostromon, Synthila)
- Mestilbol (diethylstilbestrol monomethyl ether) (Monomestro or Monomestrol)
See also
- List of estrogens
- List of progestogen esters
- List of androgen esters
- List of combined sex-hormonal preparations
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 IndexNominum2000. Taylor & Francis US. 2000. p. 404. ISBN 978-3-88763-075-1. https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA404. Retrieved 29 May 2012.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 A. D. Roberts (1991). Dictionary of Steroids: Chemical Data, Structures, and Bibliographies. CRC Press. p. 415. ISBN 978-0-412-27060-4. https://books.google.com/books?id=qw5X0NK1A90C&pg=PA415. Retrieved 20 May 2012.
- ↑ Ferin, J. (1952). "Relative duration of action of natural and synthetic estrogens administered parenterally in women with estrogen deficiency". The Journal of Clinical Endocrinology & Metabolism 12 (1): 28–35. doi:10.1210/jcem-12-1-28. ISSN 0021-972X. PMID 14907837.
- ↑ "R&D Research". http://www.evestra.com/index-Dateien/Page1242.htm.
- ↑ "Estradiol prodrugs (EP) for efficient oral estrogen treatment and abolished effects on estrogen modulated liver functions". J. Steroid Biochem. Mol. Biol. 165 (Pt B): 305–311. January 2017. doi:10.1016/j.jsbmb.2016.07.008. PMID 27449818.
- ↑ "A prodrug design for improved oral absorption and reduced hepatic interaction". Bioorg. Med. Chem. 25 (20): 5569–5575. October 2017. doi:10.1016/j.bmc.2017.08.027. PMID 28886996.
- ↑ Nickisch, K., Santhamma, B., Ahmed, G., Meece, F., Elger, W., Wyrwa, R., & Nair, H. (2017). U.S. Patent No. 9,745,338. Washington, DC: U.S. Patent and Trademark Office. https://patents.google.com/patent/US9745338B2/en
- ↑ IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 388–. ISBN 978-92-832-1291-1. https://books.google.com/books?id=aGDU5xibtNgC&pg=PA388.
- ↑ Vizzone, A.; Murari, G. (November 1966). "[Estradiol esters (3-monobenzoate and 3-benzoate-17-beta-acetate) in the therapy of the surgical menopause syndrome. Experimental and clinical results]". Quaderni di Clinica Ostetrica e Ginecologica 21 (11): 779–790. PMID 5999221.
- ↑ 10.0 10.1 10.2 "Prodrugs for improved oral beta-estradiol bioavailability". Pharm. Res. 5 (1): 44–7. January 1988. doi:10.1023/A:1015863412137. PMID 3244608.
- ↑ 11.0 11.1 11.2 Lokind, Kenneth B.; Lorenzen, Finn Hjort; Bundgaard, Hans (1991). "Oral bioavailability of 17β-estradiol and various ester prodrugs in the rat". International Journal of Pharmaceutics 76 (1–2): 177–182. doi:10.1016/0378-5173(91)90356-S. ISSN 0378-5173.
- ↑ 12.0 12.1 "Oral long-lasting estrogenic activity of estradiol 3-benzoate 17-cyclooctenyl ether". Steroids 20 (5): 627–38. November 1972. doi:10.1016/0039-128X(72)90020-7. PMID 4654978.
- ↑ "Effect of two orally active estradiol derivatives on sulfobromphthalein retention in rats". Pharmacol Res Commun 6 (2): 135–45. April 1974. doi:10.1016/s0031-6989(74)80021-4. PMID 4438394.
- ↑ Ralph I. Dorfman (5 December 2016). Steroidal Activity in Experimental Animals and Man. Elsevier Science. pp. 36–. ISBN 978-1-4832-7299-3. https://books.google.com/books?id=BbLfBAAAQBAJ&pg=PA36.
- ↑ Janocko, Laura; Larner, Janice M.; Hochberg, Richard B. (1984). "The Interaction of C-17 Esters of Estradiol with the Estrogen Receptor*". Endocrinology 114 (4): 1180–1186. doi:10.1210/endo-114-4-1180. ISSN 0013-7227. PMID 6705734.
- ↑ "Oral replacement with estradiol-cyclooctyl acetate: a new estradiol analogue. Effects on serum lipids, proteins, gonadotrophins, estrogens and uterine endometrial morphology". Gynecol. Obstet. Invest. 20 (2): 84–90. 1985. doi:10.1159/000298978. PMID 3932144.
- ↑ "Effects of estradiol decanoate in ovariectomized women". J. Endocrinol. Invest. 1 (2): 101–6. 1978. doi:10.1007/BF03350355. PMID 755846.
- ↑ 18.0 18.1 "The duration of activity of the benziloyl hydrazones of testosterone-17-heptanoate, estrone-3-heptanoate and 17α-hydroxy-progesterone-17-heptanoate". Endocrinology 65 (3): 508–511. 1959. doi:10.1210/endo-65-3-508. ISSN 0013-7227. PMID 13828402.
- ↑ George W.A Milne (8 May 2018). Drugs: Synonyms and Properties: Synonyms and Properties. Taylor & Francis. pp. 1406–. ISBN 978-1-351-78989-9. https://books.google.com/books?id=xUlaDwAAQBAJ&pg=PT1406.
- ↑ 20.0 20.1 "Novel oestrogen sulfamates: a new approach to oral hormone therapy". Expert Opin Investig Drugs 7 (4): 575–89. April 1998. doi:10.1517/13543784.7.4.575. PMID 15991994.
- ↑ "Sulfamates of various estrogens are prodrugs with increased systemic and reduced hepatic estrogenicity at oral application". J. Steroid Biochem. Mol. Biol. 55 (3–4): 395–403. December 1995. doi:10.1016/0960-0760(95)00214-6. PMID 8541236.
- ↑ 22.0 22.1 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PR2.
- ↑ "A prodrug approach to increasing the oral potency of a phenolic drug. 1. Synthesis, characterization, and stability of an O-(imidomethyl) derivative of 17 beta-estradiol". J Pharm Sci 83 (10): 1477–81. October 1994. doi:10.1002/jps.2600831022. PMID 7884673.
- ↑ "A prodrug approach to increasing the oral potency of a phenolic drug. Part 2. Pharmacodynamics and preliminary bioavailability of an orally administered O-(imidomethyl) derivative of 17 beta-estradiol". J Pharm Sci 84 (2): 174–8. February 1995. doi:10.1002/jps.2600840210. PMID 7738796.
- ↑ 25.0 25.1 Thomas L. Lemke; David A. Williams (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1395–. ISBN 978-1-60913-345-0. https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1395.
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