Estradiol 3-saccharinylmethyl ether

Estradiol 3-saccharinylmethyl ether (E2SME), also known as 3-O-(saccharinylmethyl)-17β-estradiol, is a synthetic estrogen and estrogen ether – specifically, the C3 saccharinylmethyl ether of estradiol – which was described in the mid-1990s and was never marketed.[2][1][3][4] It is a prodrug of estradiol and appears to be partially protected from first-pass metabolism in the liver and intestines with oral administration, showing greatly improved oral potency compared to estradiol.[1][3][4]

Estradiol 3-saccharinylmethyl ether
Clinical data
Other namesE2SME; 3-O-(Saccharinylmethyl)-17β-estradiol; 3-O-(Saccharinylmethyl)estra-1,3,5(10)-triene-3,17β-diol
Routes of
administration		By mouth[1]
Drug classEstrogen
Identifiers
  • 2-[[(8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl]oxymethyl]-1,1-dioxo-1,2-benzothiazol-3-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC26H29NO5S
Molar mass467.58 g·mol−1
3D model (JSmol)
  • C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=C3C=CC(=C4)OCN5C(=O)C6=CC=CC=C6S5(=O)=O
  • InChI=1S/C26H29NO5S/c1-26-13-12-19-18-9-7-17(14-16(18)6-8-20(19)22(26)10-11-24(26)28)32-15-27-25(29)21-4-2-3-5-23(21)33(27,30)31/h2-5,7,9,14,19-20,22,24,28H,6,8,10-13,15H2,1H3/t19-,20-,22+,24+,26+/m1/s1
  • Key:QNUCLUWOICXPIY-QETBJLDASA-N

E2SME has been found to be 9-fold as potent as estradiol by the oral route in rats.[1][4] Similarly, its bioavailability (16%) was 5-fold greater than that of estradiol via the oral route in rats, and the elimination half-life of released estradiol was 5- to 7-fold longer than that of regular estradiol.[1][3][4] Conversely, when E2SME and estradiol were given intravenously in rats, there was no difference between them in terms of potency.[1] In vitro studies revealed that E2SME is not hydrolyzed to estradiol enzymatically but rather is hydrolyzed chemically in biological media such as plasma, apparently dependent on the concentration of protein.[1]

See also

References
  1. Patel J, Katovich MJ, Sloan KB, Curry SH, Prankerd RJ (February 1995). "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. doi:10.1002/jps.2600840210. PMID 7738796.
  2. Patel JU, Prankerd RJ, Sloan KB (October 1994). "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. doi:10.1002/jps.2600831022. PMID 7884673.
  3. Michael Oettel; Ekkehard Schillinger (6 December 2012). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. pp. 263–. ISBN 978-3-642-60107-1.
  4. Aungst, Bruce J.; Matz, Nicole (2007). "Prodrugs to Reduce Presystemic Metabolism". Prodrugs. Biotechnology: Pharmaceutical Aspects. Vol. V. pp. 339–355. doi:10.1007/978-0-387-49785-3_8. ISBN 978-0-387-49782-2.



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