10β,17β-Dihydroxyestra-1,4-dien-3-one

10β,17β-Dihydroxyestra-1,4-dien-3-one
Clinical data
Other namesDHED; Estradiol paraquinol; Estra-1,4-diene-10β,17β-diol-3-one
Routes of
administration		By mouth[1]
Drug classEstrogen
Identifiers
IUPAC name
  • (8S,9S,10S,13S,14S,17S)-10,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC18H24O3
Molar mass288.387 g·mol−1
3D model (JSmol)
SMILES
  • C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=CC(=O)C=C[C@]34O
InChI
  • InChI=1S/C18H24O3/c1-17-8-7-15-13(14(17)4-5-16(17)20)3-2-11-10-12(19)6-9-18(11,15)21/h6,9-10,13-16,20-21H,2-5,7-8H2,1H3/t13-,14-,15-,16-,17-,18+/m0/s1
  • Key:UIKDFTLKOKNUJP-UGDFAFBOSA-N

10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED), also known as estradiol paraquinol, is an orally active, centrally selective estrogen and a biosynthetic prodrug of estradiol.[2][1][3][4]

Upon systemic administration, regardless of route of administration, DHED has been found to rapidly and selectively convert into estradiol in the brain, whereas no such conversion occurs in the rest of the body.[2][1][3] Moreover, DHED itself possesses no estrogenic activity, requiring transformation into estradiol for its estrogenicity.[2][1][3] As such, the drug shows selective estrogenic effects in the brain (e.g., alleviation of hot flashes, neuroprotection) that are said to be identical to those of estradiol, whereas estrogenic effects elsewhere in the body are not observed.[2][1][3]

DHED has been proposed as a possible novel estrogenic treatment for neurological and psychiatric conditions associated with hypoestrogenism (e.g., menopausal hot flashes, depression, cognitive decline, Alzheimer's disease, and stroke) that uniquely lacks potentially detrimental estrogenic side effects in the periphery.[2][1][3]

References

  1. 1 2 3 4 5 6 Merchenthaler I, Lane M, Sabnis G, Brodie A, Nguyen V, Prokai L, Prokai-Tatrai K (2016). "Treatment with an orally bioavailable prodrug of 17β-estradiol alleviates hot flushes without hormonal effects in the periphery". Sci Rep. 6: 30721. Bibcode:2016NatSR...630721M. doi:10.1038/srep30721. PMC 4967894. PMID 27477453.
  2. 1 2 3 4 5 Prokai L, Nguyen V, Szarka S, Garg P, Sabnis G, Bimonte-Nelson HA, McLaughlin KJ, Talboom JS, Conrad CD, Shughrue PJ, Gould TD, Brodie A, Merchenthaler I, Koulen P, Prokai-Tatrai K (2015). "The prodrug DHED selectively delivers 17β-estradiol to the brain for treating estrogen-responsive disorders". Sci Transl Med. 7 (297): 297ra113. doi:10.1126/scitranslmed.aab1290. PMC 4591937. PMID 26203081.
  3. 1 2 3 4 5 Tschiffely AE, Schuh RA, Prokai-Tatrai K, Prokai L, Ottinger MA (2016). "A comparative evaluation of treatments with 17β-estradiol and its brain-selective prodrug in a double-transgenic mouse model of Alzheimer's disease". Horm Behav. 83: 39–44. doi:10.1016/j.yhbeh.2016.05.009. PMC 4950979. PMID 27210479.
  4. ↑ Cappelletti, Maurand M. (2016). Estrogens, androgens, and the hormonal modulation of female primate sexual motivation in rhesus monkeys (Thesis). ProQuest 1835777256.


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