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 names	E2SME; 3-O-(Saccharinylmethyl)-17β-estradiol; 3-O-(Saccharinylmethyl)estra-1,3,5(10)-triene-3,17β-diol
Routes of administration	By mouth[1]
Drug class	Estrogen
Identifiers
IUPAC name 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	157231-19-1
PubChem CID	177989
ChemSpider	154944
UNII	AEF2Q624EL
CompTox Dashboard (EPA)	DTXSID40935645
Chemical and physical data
Formula	C26H29NO5S
Molar mass	467.58 g·mol−1
3D model (JSmol)	Interactive image
SMILES 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 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

• List of estrogen esters § Ethers of steroidal estrogens