This page uses content from Wikipedia and is licensed under CC BY-SA.

Estradiol stearate

Estradiol stearate
Estradiol stearate structure.svg
Clinical data
Trade namesDepofollan
Other namesE2-17-St; Estradiol octadecanoate; Estradiol 17β-stearate; Estradiol 17β-octadecanoate
Routes of
administration
Intramuscular injection
Drug classEstrogen; Estrogen ester
Identifiers
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC36H58O3
Molar mass538.857 g·mol−1
3D model (JSmol)

Estradiol stearate (E2-17-St), also known as estradiol octadecanoate and sold under the brand name Depofollan, is a naturally occurring estrogen and an estrogen ester – specifically, the C17β stearate ester of estradiol.[1][2][3][4][5] It occurs in the body as a very long-lasting metabolite and prohormone of estradiol.[5] The compound is one of the components that collectively constitute lipoidal estradiol, another of which is estradiol palmitate.[6][5] It is extremely lipophilic and hydrophobic.[5] Estradiol stearate has no affinity for the estrogen receptor, requiring transformation into estradiol via esterases for its estrogenic activity.[7][8][5] The compound does not bind to sex hormone-binding globulin or α-fetoprotein, instead being transported by lipoproteins such as high-density lipoprotein and low-density lipoprotein.[5]

In addition to its endogenous role, estradiol stearate was previously available as a pharmaceutical drug for use via depot intramuscular injection.[1][2] The medication was introduced between 1938 and 1941 under the brand name Depofollan.[9][10] It has been used to treat prostate cancer.[11][12] Estradiol stearate is a long-acting estrogen[13][10] and is said to have been the first long-acting estrogen used in medicine, although it was never widely employed.[10] It was reported to have a duration of more than one month.[10] The medication was provided as an oil solution in ampoules containing 15 mg estradiol stearate.[13][12] It was manufactured by Chinoin, a Hungarian pharmaceutical company.[13][12][9][14] The compound was studied by Karl Miescher in 1938[15] and was patented by Miescher and Chinoin in 1939 and 1941, respectively.[16][17] A similar long-acting estradiol ester is estradiol undecylate, which has 11 carbon atoms instead of the 18 carbon atoms in estradiol stearate.[1][2]

Structural properties of selected estradiol esters

Estrogen Structure Ester(s) Relative
mol. weight
Relative
E2 contentb
logPc
Position(s) Moiet(ies) Type Lengtha
Estradiol
Estradiol.svg
1.00 1.00 4.0
Estradiol acetate
Estradiol 3-acetate.svg
C3 Ethanoic acid Straight-chain fatty acid 2 1.15 0.87 2.8–3.9
Estradiol benzoate
Estradiol benzoate.svg
C3 Benzenecarboxylic acid Aromatic fatty acid – (~4–5) 1.38 0.72 4.5–5.7
Estradiol dipropionate
Estradiol dipropionate.svg
C3, C17β Propanoic acid (×2) Straight-chain fatty acid 3 (×2) 1.41 0.71 4.3
Estradiol valerate
Estradiol valerate.svg
C17β Pentanoic acid Straight-chain fatty acid 5 1.31 0.76 5.8–6.0
Estradiol cypionate
Estradiol 17 beta-cypionate.svg
C17β Cyclopentylpropanoic acid Aromatic fatty acid – (~6) 1.46 0.69 6.5–7.1
Estradiol benzoate butyrate
Estradiolbutyratebenzoate structure.png
C3, C17β Benzoic acid, butyric acid Mixed fatty acid – (~6, 2) 1.64 0.61 5.9
Estradiol enantate
Estradiol enanthate.png
C17β Heptanoic acid Straight-chain fatty acid 7 1.41 0.71 7.0
Estradiol dienantate
Estradiol dienanthate.svg
C3, C17β Heptanoic acid (×2) Straight-chain fatty acid 7 (×2) 1.82 0.55 8.1–9.1
Estradiol undecylate
Estradiol undecylate.svg
C17β Undecanoic acid Straight-chain fatty acid 11 1.62 0.62 9.2
Estradiol stearate
Estradiol stearate structure.svg
C17β Octadecanoic acid Straight-chain fatty acid 18 1.98 0.51 12.2
Estradiol distearate
Estradiol distearate.svg
C3, C17β Octadecanoic acid (×2) Straight-chain fatty acid 18 (×2) 2.96 0.34 20.2
Estradiol sulfate
Estradiol sulfate.svg
C3 Sulfuric acid Non-fatty acid 1.29 0.77 0.3–3.8
Estradiol glucuronide
Estradiol sulfate.svg
C17β Glucuronic acid Non-fatty acid 1.65 0.61 2.1–2.7
Estramustine phosphated
Estramustine phosphate.svg
C3, C17β Normustine, phosphoric acid Non-fatty acid 1.91 0.52 2.9–5.0
Polyestradiol phosphatee
Polyestradiol phosphate.svg
C3–C17β Phosphoric acid Non-fatty acid 1.23f 0.81f 2.9g
Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids. b = Relative estradiol content by weight (i.e., relative estrogenic potency). c = Experimental or predicted octanol/water partition coefficient (i.e., lipophilicity/hydrophobicity). Retrieved from PubChem and DrugBank. d = Also known as estradiol normustine phosphate. e = Polymer of estradiol phosphate (~13 repeat units). f = Relative molecular weight or estradiol content per repeat unit. g = logP of repeat unit (i.e., estradiol phosphate). Sources: See individual articles.

See also

References

  1. ^ a b c J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. p. 898. ISBN 978-1-4757-2085-3.
  2. ^ a b c Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 405–. ISBN 978-3-88763-075-1.
  3. ^ Martin Negwer (1987). Organic-chemical Drugs and Their Synonyms: (an International Survey). VCH Publishers. ISBN 978-0-89573-552-2. Estra-1,3,5(10)-triene-3,173-diol 17-octadecanoate = 3,173-Estradiol 17-stearate = (173)-Estra-1,3,5- (10)-triene-3,17-diol 17-octadecanoate (e) S Depofollan, Estradiol stearate, Ostradiolstearat U Depot-estrogen 8103
  4. ^ Edith Josephy; F. Radt (1956). Elsevier's Encyclopædia of Organic Chemistry. pp. 1974–1976.
  5. ^ a b c d e f Hochberg RB, Pahuja SL, Larner JM, Zielinski JE (1990). "Estradiol-fatty acid esters. Endogenous long-lived estrogens". Ann. N. Y. Acad. Sci. 595: 74–92. doi:10.1111/j.1749-6632.1990.tb34284.x. PMID 2197972.
  6. ^ Michael Oettel; Ekkehard Schillinger (6 December 2012). Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens. Springer Science & Business Media. pp. 235–237. ISBN 978-3-642-58616-3.
  7. ^ 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.
  8. ^ Vazquez-Alcantara, Marco Aurelio; Menjivar, Marta; Garcia, Gustavo A.; Díaz-Zagoya, Juan C.; Garza-Flores, Josue (1989). "Long-acting estrogenic responses of estradiol fatty acid esters". Journal of Steroid Biochemistry. 33 (6): 1111–1118. doi:10.1016/0022-4731(89)90417-2. ISSN 0022-4731.
  9. ^ a b Antalné, S., Géza, B., István, B., & Dezső, K. (1996). A Chinoin története (1910–1995). [www.gyogyszeresztortenet.hu] From the middle of the vitamin D and hannincas years, the research and production of steroid sex hormones was directed by Rezső Weisz. (n) In the latter, the collection of animal raw materials, in addition to chemical operations, required considerable organizational work similar to that of insulin. The intensification of attempts to produce steroid hormones and synthetic steroids, estrogens, over four years may have surpassed even 36 studies of sulfone JDid. Weisz et al., Primarily Kálmán Lányi, developed the most important estrone derivatives of industrial and therapeutic interest, Hogival (estrone acetate), Acrafalin (estradiol propionate) and Depofollan (estradiol stearate), which were marketed in 1938-1940.
  10. ^ a b c d Orvostudomány. Magyar Tudomanyos Akadémia V. Orvosi Tudományok Osztálya. 1960. p. 11.
  11. ^ Medgyaszay, A. (1963). "Intraokularer Druck und Hormonbehandlung". Ophthalmologica. 145 (3): 243–248. doi:10.1159/000304442. ISSN 1423-0267.
  12. ^ a b c Camillo Sellei (1970). Chemotherapy of Neoplastic Diseases. Acad. Press. p. 251.
  13. ^ a b c Endokrinologie. Johann Ambrosius Barth Verlag. 1951.
  14. ^ Alkaloida Vegyészeti Gyár Rt, Tiszavasvári T. Novák K., Hermecz I. szerk. (2005): Esti beszélgetés – Magyar Gyógyszerkutatók portréi. MTA Gyógyszerkémiai és Gyógyszertechnológiai Munkabizottsága, Budapest [www.gyogyszeresztortenet.hu] Archived 2016-08-05 at the Wayback Machine "Chinoin has achieved good results in the steroid hormones, synthetic steroids, and estrogens since the twenties, protected by 36 patents. The company was one of the first in the world to produce vitamin D, but was also a successful product for Hogival (estrone acetate), Acrofollin (estradiol propionate), Depofollan (estradiol stearate), Acrolutin (progesterone)."
  15. ^ Miescher K, Scholz C, Tschopp E (August 1938). "The activation of female sex hormones: Mono-esters of alpha-oestradiol". Biochem. J. 32 (8): 1273–80. doi:10.1042/bj0321273b. PMC 1264184. PMID 16746750.
  16. ^ [patents.google.com]
  17. ^ [patents.google.com]