Chemical compound
Pharmaceutical compound
Methallenestril Clinical data Trade names Cur-men, Ercostrol, Geklimon, Novestrine, Vallestril (also spelled Vallestrol or Vallestryl) Other names Methallenoestril; Methallenestrol; Methallenoestrol; Horeau's acid; Allenestrol 6-methyl ether; α,α-Dimethyl-β-ethylallenolic acid 6-methyl ether; β-Ethyl-6-methoxy-α,α-dimethyl-2-naphthalenepropionic acid Routes of By mouth Drug class Nonsteroidal estrogen ATC code Identifiers CAS Number PubChem CID ChemSpider UNII CompTox Dashboard (EPA) ECHA InfoCard 100.007.485 Chemical and physical data Formula C 18 H 22 O 3 Molar mass −1 3D model (JSmol ) InChI=1S/C18H22O3/c1-5-16(18(2,3)17(19)20)14-7-6-13-11-15(21-4)9-8-12(13)10-14/h6-11,16H,5H2,1-4H3,(H,19,20)
Key:KHLJKRBMZVNZOC-UHFFFAOYSA-N
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Methallenestril (INN Tooltip International Nonproprietary Name ) (brand namesCur-men ,Ercostrol ,Geklimon ,Novestrine ,Vallestril ), also known asmethallenoestril (BAN Tooltip British Approved Name ) and asmethallenestrol , as well asHoreau's acid ,[ 1] [ 2] synthetic nonsteroidal estrogen and aderivative ofallenolic acid andallenestrol (specifically, amethyl ether of it) that was formerly used to treatmenstrual issues but is now no longer marketed.[ 3] [ 4] [ 5] [ 6] analogue ofbisdehydrodoisynolic acid , and although methallenestril is potentlyestrogenic in rats, in humans it is only weakly so in comparison.[ 7] Vallestril was a brand of methallenestril issued byG. D. Searle & Company in the 1950s.[ 8] by mouth .[ 9] diethylstilbestrol , 4 mgdienestrol , 20 mghexestrol , 25 mgestrone , 2.5 mgconjugated estrogens , and 0.05 mgethinylestradiol .[ 9]
The chemical synthesis has been described:[ 10] [ 11] [ 12] [ 13] [ 14]
The Grignard reaction between 2-propionyl-6-methoxynaphthalene (promen ) [2700-47-2] (1 ) and Ethyl 2-bromoisobutyrate [600-00-0] (2 ) occurs to give Ethyl beta-ethyl-beta-hydroxy-6-methoxy-alpha,alpha-dimethylnaphthalene-2-propionate [85536-81-8] (3 ). Dehydration of the carbinol in aqueous lye may be accompanied by saponification of the ester (although not in the patented version) to give [60533-05-3] (4 ). Re-esterification with diazomethane gave (5 ). Catalytic hydrogenation of the olefin led to PC608080 (6 ). Saponification of the ester completed the synthesis of Methallenestril (7 ).
An alternative method is described in the patent that relies on 2-cyano-6-methoxynaphthalene (cyanonerolin ) [67886-70-8]. The precusor to this is described in a Hoechst patent.[ 15]
^ Heftmann E (1970).Steroid Biochemistry ISBN 9780123366504 ^ Dodds EC (March 1949)."Synthetic oestrogens" .The Journal of Pharmacy and Pharmacology .1 (3):137– 147.doi :10.1111/j.2042-7158.1949.tb12391.x PMID 18114509 .S2CID 221921908 . ^ Ganellin CR, Triggle DJ (21 November 1996).Dictionary of Pharmacological Agents ISBN 978-0-412-46630-4 ^ Morton IK, Hall JM (6 December 2012).Concise Dictionary of Pharmacological Agents: Properties and Synonyms ISBN 978-94-011-4439-1 ^ Thomas JA, Keenan EJ (1986)."Estrogens and Estrogenic Compounds" .Principles of Endocrine Pharmacology . Springer Science & Business Media. p. 136.ISBN 978-1-4684-5036-1 ^ Herbai G, Ljunghall S (1983). "Normalization of hypercalcaemia of primary hyperparathyroidism by treatment with methallenestril, a synthetic oestrogen with low oestrogenicity".Urologia Internationalis .38 (6):371– 373.doi :10.1159/000280925 .PMID 6659184 . ^ Kirk RE, Othmer DF (1980).Encyclopedia of chemical technology ISBN 978-0-471-02065-3 ^ Catalog of Copyright Entries: Third Series ^a b Swyer GI (April 1959)."The oestrogens" .British Medical Journal .1 (5128):1029– 1031.doi :10.1136/bmj.1.5128.1029 .PMC 1993181 PMID 13638626 . ^ Wieland, P., Miescher, K. (January 1948)."Abkömmlinge alkylierter β‐Naphtyl‐valeriansäuren. Über oestrogene Carbonsäuren XXVI" .Helvetica Chimica Acta .31 (6):1844– 1854.doi :10.1002/hlca.19480310650 . ^ Horeau Alain & Jacques Jean,U.S. patent 2,547,123 ^ Gay, R. et al, Bull. Soc. Chim. Fr., 1955, 955. ^ Jacques; Horeau Bulletin de la Societe Chimique de France, 1948 , p. 711,715. ^ Dubois,J.C. et al. Bulletin de la Societe Chimique de France, 1967 , p. 1827 – 1833. ^ Theodor Papenfuhs & Kurt Gengnagel,U.S. patent 4,137,272
Estrogens
ER Tooltip Estrogen receptor agonistsSteroidal: Alfatradiol Certainandrogens /anabolic steroids (e.g.,testosterone ,testosterone esters ,methyltestosterone ,metandienone ,nandrolone esters ) (via estrogenic metabolites) Certainprogestins (e.g.,norethisterone ,noretynodrel ,etynodiol diacetate ,tibolone ) Clomestrone Cloxestradiol acetate Conjugated estriol Conjugated estrogens Epiestriol Epimestrol Esterified estrogens Estetrol † Estradiol Estradiol esters (e.g.,estradiol acetate ,estradiol benzoate ,estradiol cypionate ,estradiol enanthate ,estradiol undecylate ,estradiol valerate ,polyestradiol phosphate ,estradiol ester mixtures (Climacteron ))Estramustine phosphate Estriol Estriol esters (e.g.,estriol succinate ,polyestriol phosphate )Estrogenic substances Estrone Estrone esters Ethinylestradiol # Hydroxyestrone diacetate Mestranol Methylestradiol Moxestrol Nilestriol Prasterone (dehydroepiandrosterone; DHEA) Promestriene Quinestradol Quinestrol Progonadotropins
Antiestrogens
ER Tooltip Estrogen receptor antagonistsSERMs Tooltip selective estrogen receptor modulators /SERDs Tooltip selective estrogen receptor downregulators )Aromatase inhibitors Antigonadotropins Androgens /anabolic steroids (e.g.,testosterone ,testosterone esters ,nandrolone esters ,oxandrolone ,fluoxymesterone )D2 receptor antagonists (prolactin releasers) (e.g.,domperidone ,metoclopramide ,risperidone ,haloperidol ,chlorpromazine ,sulpiride )GnRH agonists (e.g.,leuprorelin ,goserelin )GnRH antagonists (e.g.,cetrorelix ,elagolix )Progestogens (e.g.,chlormadinone acetate ,cyproterone acetate ,gestonorone caproate ,hydroxyprogesterone caproate ,medroxyprogesterone acetate ,megestrol acetate )Others
ER Tooltip Estrogen receptor
Agonists Steroidal: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol 3α-Androstanediol 3α,5α-Dihydrolevonorgestrel 3β,5α-Dihydrolevonorgestrel 3α-Hydroxytibolone 3β-Hydroxytibolone 3β-Androstanediol 4-Androstenediol 4-Androstenedione 4-Fluoroestradiol 4-Hydroxyestradiol 4-Hydroxyestrone 4-Methoxyestradiol 4-Methoxyestrone 5-Androstenediol 7-Oxo-DHEA 7α-Hydroxy-DHEA 7α-Methylestradiol 7β-Hydroxyepiandrosterone 8,9-Dehydroestradiol 8,9-Dehydroestrone 8β-VE2 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) 11β-Chloromethylestradiol 11β-Methoxyestradiol 15α-Hydroxyestradiol 16-Ketoestradiol 16-Ketoestrone 16α-Fluoroestradiol 16α-Hydroxy-DHEA 16α-Hydroxyestrone 16α-Iodoestradiol 16α-LE2 16β-Hydroxyestrone 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol) 17α-Estradiol (alfatradiol )17α-Dihydroequilenin 17α-Dihydroequilin 17α-Epiestriol (16α-hydroxy-17α-estradiol) 17α-Ethynyl-3α-androstanediol 17α-Ethynyl-3β-androstanediol 17β-Dihydroequilenin 17β-Dihydroequilin 17β-Methyl-17α-dihydroequilenin Abiraterone Abiraterone acetate Alestramustine Almestrone Anabolic steroids (e.g.,testosterone andesters ,methyltestosterone ,metandienone (methandrostenolone) ,nandrolone andesters , many others; via estrogenic metabolites)Atrimustine Bolandiol Bolandiol dipropionate Butolame Clomestrone Cloxestradiol Conjugated estriol Conjugated estrogens Cyclodiol Cyclotriol DHEA DHEA-S ent -EstradiolEpiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol) Epimestrol Equilenin Equilin ERA-63 (ORG-37663) Esterified estrogens Estetrol Estradiol Estramustine Estramustine phosphate Estrapronicate Estrazinol Estriol Estrofurate Estrogenic substances Estromustine Estrone Etamestrol (eptamestrol) Ethinylandrostenediol Ethinylestradiol Ethinylestriol Ethylestradiol Etynodiol Etynodiol diacetate Hexolame Hippulin Hydroxyestrone diacetate Lynestrenol Lynestrenol phenylpropionate Mestranol Methylestradiol Moxestrol Mytatrienediol Nilestriol Norethisterone Noretynodrel Orestrate Pentolame Prodiame Prolame Promestriene RU-16117 Quinestradol Quinestrol Tibolone Xenoestrogens: Anise -related (e.g.,anethole ,anol ,dianethole ,dianol ,photoanethole )Chalconoids (e.g.,isoliquiritigenin ,phloretin ,phlorizin (phloridzin) ,wedelolactone )Coumestans (e.g.,coumestrol ,psoralidin )Flavonoids (incl.7,8-DHF ,8-prenylnaringenin ,apigenin ,baicalein ,baicalin ,biochanin A ,calycosin ,catechin ,daidzein ,daidzin ,ECG ,EGCG ,epicatechin ,equol ,formononetin ,glabrene ,glabridin ,genistein ,genistin ,glycitein ,kaempferol ,liquiritigenin ,mirificin ,myricetin ,naringenin ,penduletin ,pinocembrin ,prunetin ,puerarin ,quercetin ,tectoridin ,tectorigenin )Lavender oil Lignans (e.g.,enterodiol ,enterolactone ,nyasol (cis -hinokiresinol) )Metalloestrogens (e.g.,cadmium )Pesticides (e.g.,alternariol ,dieldrin ,endosulfan ,fenarimol ,HPTE ,methiocarb ,methoxychlor ,triclocarban ,triclosan )Phytosteroids (e.g.,digitoxin (digitalis ),diosgenin ,guggulsterone )Phytosterols (e.g.,β-sitosterol ,campesterol ,stigmasterol )Resorcylic acid lactones (e.g.,zearalanone ,α-zearalenol ,β-zearalenol ,zearalenone ,zeranol (α-zearalanol) ,taleranol (teranol, β-zearalanol) )Steroid -like (e.g.,deoxymiroestrol ,miroestrol )Stilbenoids (e.g.,resveratrol ,rhaponticin )Synthetic xenoestrogens (e.g.,alkylphenols ,bisphenols (e.g.,BPA ,BPF ,BPS ),DDT ,parabens ,PBBs ,PHBA ,phthalates ,PCBs )Others (e.g.,agnuside ,rotundifuran ) MixedSERMs Tooltip Selective estrogen receptor modulators ) Antagonists Coregulator-binding modulators: ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
