Jump to content

RU-16117

From Wikipedia, the free encyclopedia
(Redirected from 11α-MeO-EE)
RU-16117
Clinical data
Other names11α-Methoxyethinylestradiol; 11α-Methoxy-17α-ethynylestradiol; 11α-Methoxy-19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol
Routes of
administration
By mouth[1]
Drug classEstrogen; Estrogen ether
Identifiers
  • (8S,9S,11R,13S,14S,17R)-17-Ethynyl-11-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H26O3
Molar mass326.436 g·mol−1
3D model (JSmol)
  • C[C@]12C[C@H]([C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=C3C=CC(=C4)O)OC
  • InChI=1S/C21H26O3/c1-4-21(23)10-9-17-16-7-5-13-11-14(22)6-8-15(13)19(16)18(24-3)12-20(17,21)2/h1,6,8,11,16-19,22-23H,5,7,9-10,12H2,2-3H3/t16-,17-,18+,19+,20-,21-/m0/s1
  • Key:MTMZZIPTQITGCY-QHOCJJNXSA-N

RU-16117 is an estrogen medication which was investigated for the potential treatment of symptoms of estrogen deficiency such as hot flashes and osteoporosis in women but was never marketed.[1] It was developed for use by mouth.[1]

Pharmacology

[edit]

Pharmacodynamics

[edit]

RU-16117 is an estrogen, or an agonist of the estrogen receptor (ER).[1][2] In mouse uterine tissue, it shows about 5 to 13% of the affinity of estradiol for the ER and about 1% of the estrogenic activity of estradiol.[2][3][4] Conversely, it shows no affinity for the androgen, progesterone, glucocorticoid, and mineralocorticoid receptors, nor any activities associated with interactions with these receptors.[2][5][3][4] While the association rate of RU-16117 to the ER is the same as that of moxestrol, it dissociates from the ER extremely rapidly at rates of about three times faster than estradiol and about 20 times faster than moxestrol.[1][6] This is similar to the case of estriol, which RU-16117 is described as sharing similarities with.[1][6] RU-16117 is described as a weak or partial estrogen or a mixed estrogen/antiestrogen.[1][2] It has been described as having highly active antiestrogenic activity with very weak uterotrophic activity.[7][2] However, higher doses and/or prolonged administration of RU-16117 have been reported to induce equivalent estrogenic responses relative to estradiol and moxestrol.[1][6]

Relative affinities (%) of RU-16117 and related steroids[5][8][3]
Compound PRTooltip Progesterone receptor ARTooltip Androgen receptor ERTooltip Estrogen receptor GRTooltip Glucocorticoid receptor MRTooltip Mineralocorticoid receptor SHBGTooltip Sex hormone-binding globulin CBGTooltip Corticosteroid binding globulin
Estradiol 2.6 7.9 100 0.6 0.13 8.7 <0.1
Estriol ? ? 15 ? ? ? ?
Ethinylestradiol 15–25 1–3 112 1–3 <1 ? ?
Moxestrol (11β-MeO-EE) 0.8 <0.1 12 3.2 <0.1 <0.2 <0.1
RU-16117 (11α-MeO-EE) 1–3 <1 13 <1 <1 ? ?
Values are percentages (%). Reference ligands (100%) were progesterone for the PRTooltip progesterone receptor, testosterone for the ARTooltip androgen receptor, E2 for the ERTooltip estrogen receptor, DEXATooltip dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, DHTTooltip dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip Corticosteroid-binding globulin.

Chemistry

[edit]

RU-16117, also known as 11α-methoxy-17α-ethynylestradiol (11α-MeO-EE) or as 11α-methoxy-17α-ethynylestra-1,3,5(10)-triene-3,17β-diol, is a synthetic estrane steroid and a derivative of estradiol.[1] It is specifically a derivative of ethinylestradiol (17α-ethynylestradiol) with a methoxy group at the C11α position.[1] The compound is the C11α isomer or C11 epimer of moxestrol (11β-methoxy-17α-ethynylestradiol).[1][9]

Synthesis

[edit]

RU-16117 is derived from Δ9,11-dehydroestradiol [Wikidata] (1). Its two hydroxy groups are first protected by the formation of benzyl ethers, giving (2) and the isolated double bond is hydrated by hydroboration, followed by oxidation with hydrogen peroxide in alkali to give (3). The newly-introduced alcohol is methylated with iodomethane to produce (4). After removal of the protecting groups by catalytic hydrogenation to form (5), the hydroxyl group in the five-membered ring is oxidized to a ketone with chromium trioxide and the product, (6), is reacted with potassium acetylide to introduce the acetylide group of the drug.[1][10]

References

[edit]
  1. ^ a b c d e f g h i j k l Raynaud JP, Azadian-Boulanger G, Bouton MM, Colin MC, Faure N, Fernand-Proulx L, et al. (April 1984). "RU 16117, an orally active estriol-like weak estrogen". Journal of Steroid Biochemistry. 20 (4B): 981–993. doi:10.1016/0022-4731(84)90008-6. PMID 6427528.
  2. ^ a b c d e Raynaud JP, Bonne C, Bouton MM, Moguilewsky M, Philibert D, Azadain-Boulanger (22 October 2013). "Screening for anti-hormones by receptor studies". In James VH, Pasqualini JR (eds.). Proceedings of the Fourth International Congress on Hormonal Steroids: Mexico City, September 1974. Elsevier Science. pp. 618–621. ISBN 978-1-4831-4566-2.
  3. ^ a b c Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, et al. (January 1980). "Steroid hormone receptors and pharmacology". Journal of Steroid Biochemistry. 12: 143–157. doi:10.1016/0022-4731(80)90264-2. PMID 7421203.
  4. ^ a b Bouton MM, Raynaud JP (August 1979). "The relevance of interaction kinetics in determining biological response to estrogens". Endocrinology. 105 (2): 509–515. doi:10.1210/endo-105-2-509. PMID 456327.
  5. ^ a b Ojasoo T, Raynaud JP (November 1978). "Unique steroid congeners for receptor studies". Cancer Research. 38 (11 Pt 2): 4186–4198. PMID 359134.
  6. ^ a b c Raynaud JP (26 January 2016). "The Mechanism of Action of Anti-hormones". In Jacob J (ed.). Receptors: Proceedings of the 7th International Congress of Pharmacology, Paris, 1978. Elsevier. pp. 261–, 266–267, 274. ISBN 978-1-4831-5796-2.
  7. ^ Kelly PA, Asselin J, Caron MG, Raynaud JP, Labrie F (January 1977). "High inhibitory activity of a new antiestrogen, RU 16117 (11alpha-methoxy ethinyl estradiol), on the development of dimethylbenz(a)anthracene-induced mammary tumors". Cancer Research. 37 (1): 76–81. PMID 187338.
  8. ^ Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen receptors". Journal of Steroid Biochemistry. 27 (1–3): 255–269. doi:10.1016/0022-4731(87)90317-7. PMID 3695484.
  9. ^ Raynaud JP, Moguilewsky M, Vannier B (22 October 2013). "Influence of rat estradiol binding protein (EBP) on estrogen binding to its receptor and on induced biological responses". In Kaye AM, Kaye M (eds.). Development of Responsiveness to Steroid Hormones: Advances in the Biosciences. Elsevier Science. pp. 61–. ISBN 978-1-4831-5308-7.
  10. ^ "RU 16117". chemdrug.com. Retrieved 2024-07-11.