RU-16117

Last updated
RU-16117
RU-16117.svg
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 class Estrogen; 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
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C21H26O3
Molar mass 326.436 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]

Contents

Pharmacology

Pharmacodynamics

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 PR Tooltip Progesterone receptor AR Tooltip Androgen receptor ER Tooltip Estrogen receptor GR Tooltip Glucocorticoid receptor MR Tooltip Mineralocorticoid receptor SHBG Tooltip Sex hormone-binding globulin CBG Tooltip Corticosteroid binding globulin
Estradiol 2.67.91000.60.138.7<0.1
Estriol  ? ?15 ? ? ? ?
Ethinylestradiol 15–251–31121–3<1 ? ?
Moxestrol (11β-MeO-EE)0.8<0.1123.2<0.1<0.2<0.1
RU-16117 (11α-MeO-EE)1–3<113<1<1 ? ?
Values are percentages (%). Reference ligands (100%) were progesterone for the PR Tooltip progesterone receptor, testosterone for the AR Tooltip androgen receptor, E2 for the ER Tooltip estrogen receptor, DEXA Tooltip dexamethasone for the GR Tooltip glucocorticoid receptor, aldosterone for the MR Tooltip mineralocorticoid receptor, DHT Tooltip dihydrotestosterone for SHBG Tooltip sex hormone-binding globulin, and cortisol for CBG Tooltip Corticosteroid-binding globulin.

Chemistry

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

RU 16117 synthesis.svg

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]

Related Research Articles

The sex hormone receptors, or sex steroid receptors, are a group of steroid hormone receptors that interact with the sex hormones, the androgens, estrogens, and progestogens, as well as with sex-hormonal agents such as anabolic steroids, progestins, and antiestrogens. They include the:

<span class="mw-page-title-main">Danazol</span> Chemical compound

Danazol, sold as Danocrine and other brand names, is a medication used in the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema and other conditions. It is taken by mouth.

<span class="mw-page-title-main">Gestrinone</span> Chemical compound

Gestrinone, sold under the brand names Dimetrose and Nemestran among others, is a medication which is used in the treatment of endometriosis. It has also been used to treat other conditions such as uterine fibroids and heavy menstrual bleeding and has been investigated as a method of birth control. Gestrinone is used alone and is not formulated in combination with other medications. It is taken by mouth or in through the vagina.

<span class="mw-page-title-main">Norgestrienone</span> Chemical compound

Norgestrienone, sold under the brand names Ogyline, Planor, and Miniplanor, is a progestin medication which has been used in birth control pills, sometimes in combination with ethinylestradiol. It was developed by Roussel Uclaf and has been registered for use only in France. Under the brand name Planor, it has been marketed in France as 2 mg norgestrienone and 50 μg ethinylestradiol tablets. It is taken by mouth.

<span class="mw-page-title-main">Trestolone</span> Chemical compound

Trestolone, also known as 7α-methyl-19-nortestosterone (MENT), is an experimental androgen/anabolic steroid (AAS) and progestogen medication which has been under development for potential use as a form of hormonal birth control for men and in androgen replacement therapy for low testosterone levels in men but has never been marketed for medical use. It is given as an implant that is placed into fat. As trestolone acetate, an androgen ester and prodrug of trestolone, the medication can also be given by injection into muscle.

<span class="mw-page-title-main">Metribolone</span> Chemical compound

Metribolone is a synthetic and orally active anabolic–androgenic steroid (AAS) and a 17α-alkylated nandrolone (19-nortestosterone) derivative which was never marketed for medical use but has been widely used in scientific research as a hot ligand in androgen receptor (AR) ligand binding assays (LBAs) and as a photoaffinity label for the AR. More precisely, metribolone is the 17α-methylated derivative of trenbolone. It was investigated briefly for the treatment of advanced breast cancer in women in the late 1960s and early 1970s, but was found to produce signs of severe hepatotoxicity at very low dosages, and its development was subsequently discontinued.

<span class="mw-page-title-main">Demegestone</span> Chemical compound

Demegestone, sold under the brand name Lutionex, is a progestin medication which was previously used to treat luteal insufficiency but is now no longer marketed. It is taken by mouth.

<span class="mw-page-title-main">Moxestrol</span> Chemical compound

Moxestrol, sold under the brand name Surestryl, is an estrogen medication which has been used in Europe for the treatment of menopausal symptoms and menstrual disorders. It is taken by mouth. In addition to its use as a medication, moxestrol has been used in scientific research as a radioligand of the estrogen receptor.

<span class="mw-page-title-main">Quingestanol acetate</span> Chemical compound

Quingestanol acetate, sold under the brand names Demovis and Pilomin among others, is a progestin medication which was used in birth control pills but is no longer marketed. It is taken by mouth.

<span class="mw-page-title-main">Methylestradiol</span> Chemical compound

Methylestradiol, sold under the brand names Ginecosid, Ginecoside, Mediol, and Renodiol, is an estrogen medication which is used in the treatment of menopausal symptoms. It is formulated in combination with normethandrone, a progestin and androgen/anabolic steroid medication. Methylestradiol is taken by mouth.

<span class="mw-page-title-main">Epiestriol</span> Chemical compound

Epiestriol, or epioestriol, also known as 16β-epiestriol or simply 16-epiestriol, as well as 16β-hydroxy-17β-estradiol, is a minor and weak endogenous estrogen, and the 16β-epimer of estriol. Epiestriol is used clinically in the treatment of acne. In addition to its estrogenic actions, epiestriol has been found to possess significant anti-inflammatory properties without glycogenic activity or immunosuppressive effects, an interesting finding that is in contrast to conventional anti-inflammatory steroids such as hydrocortisone.

<span class="mw-page-title-main">17α-Epiestriol</span> Chemical compound

17α-Epiestriol, or simply 17-epiestriol, also known as 16α-hydroxy-17α-estradiol or estra-1,3,5(10)-triene-3,16α,17α-triol, is a minor and weak endogenous estrogen, and the 17α-epimer of estriol. It is formed from 16α-hydroxyestrone. In contrast to other endogenous estrogens like estradiol, 17α-epiestriol is a selective agonist of the ERβ. It is described as a relatively weak estrogen, which is in accordance with its relatively low affinity for the ERα. 17α-Epiestriol has been found to be approximately 400-fold more potent than estradiol in inhibiting tumor necrosis factor α (TNFα)-induced vascular cell adhesion molecule 1 (VCAM-1) expression in vitro.

<span class="mw-page-title-main">Trimethyltrienolone</span> Chemical compound

Trimethyltrienolone (TMT), also known by its developmental code name R-2956 or RU-2956, is an antiandrogen medication which was never introduced for medical use but has been used in scientific research.

<span class="mw-page-title-main">Dimethyltrienolone</span> Anabolic–androgenic steroid

Dimethyltrienolone is a synthetic, orally active, and extremely potent anabolic–androgenic steroid (AAS) and 17α-alkylated 19-nortestosterone (nandrolone) derivative which was never marketed for medical use. It has among the highest known affinity of any AAS for the androgen receptors, and has been said to be perhaps the most potent AAS to have ever been developed.

<span class="mw-page-title-main">2-Hydroxyestrone</span> Chemical compound

2-Hydroxyestrone (2-OHE1), also known as estra-1,3,5(10)-trien-2,3-diol-17-one, is an endogenous, naturally occurring catechol estrogen and a major metabolite of estrone and estradiol. It is formed irreversibly from estrone in the liver and to a lesser extent in other tissues via 2-hydroxylation mediated by cytochrome P450 enzymes, mainly the CYP3A and CYP1A subfamilies. 2-OHE1 is the most abundant catechol estrogen in the body.

<span class="mw-page-title-main">17α-Methyl-19-norprogesterone</span> Chemical compound

17α-Methyl-19-norprogesterone, also known as 17α-methyl-19-norpregn-4-ene-3,20-dione, is a progestin which was never marketed. It is a derivative of progesterone, and is the combined derivative of 17α-methylprogesterone and 19-norprogesterone. The drug is the parent compound of a subgroup of the 19-norprogesterone group of progestins, which includes demegestone, promegestone, and trimegestone.

<span class="mw-page-title-main">Dimethyldienolone</span> Chemical compound

Dimethyldienolone, or 7α,17α-dimethyldienolone, also known as δ9-7α,17α-dimethyl-19-nortestosterone or as 7α,17α-dimethylestr-4,9-dien-17β-ol-3-one, is a 17α-alkylated androgen/anabolic steroid of the 19-nortestosterone group which was never marketed. It is closely related to dimethyltrienolone, as well as to mibolerone and metribolone. Dimethyldienolone shows high affinity for the androgen and progesterone receptors.

<span class="mw-page-title-main">7α-Methylestradiol</span> Chemical compound

7α-Methylestradiol (7α-Me-E2), also known as 7α-methylestra-1,3,5(10)-triene-3,17β-diol, is a synthetic estrogen and an active metabolite of the androgen/anabolic steroids trestolone/Methandienone. It is considered to be responsible for the estrogenic activity of trestolone. The compound shows about higher affinity for the estrogen receptor than estradiol.

<span class="mw-page-title-main">Estriol (medication)</span> Chemical compound

Estriol (E3), sold under the brand name Ovestin among others, is an estrogen medication and naturally occurring steroid hormone which is used in menopausal hormone therapy. It is also used in veterinary medicine as Incurin to treat urinary incontinence due to estrogen deficiency in dogs. The medication is taken by mouth in the form of tablets, as a cream that is applied to the skin, as a cream or pessary that is applied in the vagina, and by injection into muscle.

<span class="mw-page-title-main">11β-Methoxyestradiol</span> Chemical compound

11β-Methoxyestradiol is a synthetic steroidal estrogen which was never marketed. It has about 86% of the relative binding affinity of estradiol for the estrogen receptor. 11β-MeOE2 is structurally related to moxestrol (11β-methoxy-17α-ethynylestradiol). 11β-MeOE2 and moxestrol are substantially more potent than their non-methoxylated analogues in mice.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 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. 1 2 3 4 5 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. 1 2 3 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. 1 2 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. 1 2 Ojasoo T, Raynaud JP (November 1978). "Unique steroid congeners for receptor studies". Cancer Research. 38 (11 Pt 2): 4186–4198. PMID   359134.
  6. 1 2 3 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.