Chemical compound
Pharmaceutical compound
Doisynoestrol Clinical data Trade names Fenocyclin, Surestrine, Surestryl Other names Diosynestrol; Fenocycline; Fenocyclin; Phenocyclin; RS-2874; Dehydrofolliculinic acid;cis -Bisdehydrodoisynolic acid 7-methyl ether; BDDA ME; NSC-56846; NSC-122041 Routes of By mouth Drug class Nonsteroidal estrogen Identifiers CAS Number PubChem CID ChemSpider UNII CompTox Dashboard (EPA) Chemical and physical data Formula C 19 H 22 O 3 Molar mass −1 3D model (JSmol ) InChI=1S/C19H22O3/c1-4-17-16-7-5-12-11-13(22-3)6-8-14(12)15(16)9-10-19(17,2)18(20)21/h5-8,11,17H,4,9-10H2,1-3H3,(H,20,21)
Key:HZZSXUIUESWVSS-UHFFFAOYSA-N
Doisynoestrol (brand namesFenocyclin ,Surestrine ,Surestryl ; former developmental code nameRS-2874 ), also known asfenocycline , as well ascis -bisdehydrodoisynolic acid 7-methyl etherBDDA ME ), is asynthetic nonsteroidal estrogen of thedoisynolic acid group that is no longer marketed.[ 1] [ 2] methyl ether ofbisdehydrodoisynolic acid .[ 1] [ 1] relative binding affinity ofestradiol for theestrogen receptor .[ 3]
The methyl ether has the same activity as the alcohol making it one of the most potent oral estrogens ever discovered.[ 4]
The chemical synthesis has been described by Johnson & Graber:[ 5] [ 6] [ 7] [ 8] [ 9] [ 10] [ 11]
TheStobbe condensation between 2-propionyl-6-methoxynaphthalene (Promen ) [2700-47-2] (1 ) anddiethyl succinate [123-25-1] (2 ) gives a mixture of unsaturated esters (3 ).Catalytic hydrogenation of the olefin andsaponification of the ester yields (4 ). Intramolecular cyclization occurs first by reaction with acetyl chloride then with aluminium trichloride in nitromethane solvent to give 1-Ethyl-7-methoxy-4-oxo-1,3,4-tetrahydro-phenanthrene-2-carboxylic acid, PC287656 (5 ).Catalytic hydrogenation in the presence ofperchloric acid led to reductive removal of the keto group in the newly formed ring giving 1-Ethyl-7-methoxy-1,2,3,4-tetrahydrophenanthrene-2-carboxylic acid, PC177705457 (6 ). Esterification of the remaining acid moiety in the presence of diazomethane gave Methyl 1-ethyl-7-methoxy-1,2,3,4-tetrahydrophenanthrene-2-carboxylate, PC151271 (7 ). Alkylation by means of triphenylmethyl sodium in the presence of iodomethane gave methyl 1-ethyl-7-methoxy-2-methyl-3,4-dihydro-1H-phenanthrene-2-carboxylate, PC162092603 (8 ). Lastly saponification of the ester completed the synthesis of Bisdehydrodoisynolic acid.
^a b c Elks J (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies ISBN 978-1-4757-2085-3 ^ Herbai G (October 1971). "Separation of growth inhibiting potency from oestrogenicity in different weak oestrogenic drugs of various chemical structures".Acta Endocrinologica .68 (2):249– 63.doi :10.1530/acta.0.0680249 .PMID 5171465 . ^ Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM (March 2000)."The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands" .Toxicol Sci .54 (1):138– 53.doi :10.1093/toxsci/54.1.138 PMID 10746941 . ^ Miescher, K. (1 December 1948)."On Doisynolic Acids, A New Class of Estrogens" Chemical Reviews .43 (3):367– 384.doi :10.1021/cr60136a001 . ^ Johnson, W. S., Graber, R. P. (July 1948)."BIS-DEHYDRODOISYNOLIC ACID" Journal of the American Chemical Society .70 (7):2612– 2613.doi :10.1021/ja01187a525 . ^ William S Johnson & Robert P Graber,U.S. patent 2,574,396 ^ William S Johnson & Robert P Graber,U.S. patent 2,683,738 ^ Heer, J., Billeter, J. R., Miescher, K. (January 1945)."Über Steroide. 43. Mitteilung. Totalsynthese der racemischen Bisdehydro‐doisynolsäuren. Über oestrogene Carbonsäuren IV" Helvetica Chimica Acta .28 (1):1342– 1354.doi :10.1002/hlca.6602801186 . ^ Miescher Karl & Anner Georg,U.S. patent 2,459,949 ^ Miescher Karl, Heer Jules, & Anner Georg,U.S. patent 2,621,208 ^ Gastambide-Odier, M. et al, Bull. Soc. Chim. Fr., 1963, 1777.
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
