DK2688570T3 - 6-substituerede estradiolderivater til anvendelse ved remyelinering af nerveaxoner - Google Patents

6-substituerede estradiolderivater til anvendelse ved remyelinering af nerveaxoner Download PDF

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DK2688570T3
DK2688570T3 DK12761491.5T DK12761491T DK2688570T3 DK 2688570 T3 DK2688570 T3 DK 2688570T3 DK 12761491 T DK12761491 T DK 12761491T DK 2688570 T3 DK2688570 T3 DK 2688570T3
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methyl
cyclopenta
decahydro
diol
methoxymethyl
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James G Yarger
Steve Nye
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Endece Llc
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Claims (14)

1. 6-substitueret estradiolderivat med formlen:
hvori "a"-ringen er valgt fra gruppen bestående af
Ri, R2, R3 og R4 er uafhængigt valgt fra gruppen bestående af H, Ci-C6 alkyl, halogen, et sulfate, et glucuronid, -OH, en sterisk krævende gruppe, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, -N(CH2)n, en fosfatgruppe og en fosfinatgruppe; R11 er valgt fra gruppen bestående af Η, 0,-¾ alkyl, halogen, et sulfat, a glucoro-nid, -S02NH2, -COOH, -CN, -CH2CN-, -NHCN-, -CHO, =CHOCH3, -COO salt, -0S02alkyl, -NH2, og -NHCO(CH2)n; X er valgt fra gruppen bestående af 0-012 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, halogen, et glucoronid, -NH2, -S02NH2, -COOH, -CN, -CH2CN, -NHCN, -CHO, -COOsalt, -0S02alkyl, -SH, -SCH3, -CH[(CH2)nCH3]COOCH3, -(CH2)mCOOCH3, -(CH2)m-0-CH3, -(CH2)m-0-(CH2)nCH3, (CH2)m-S-CH3, -(CH2)m-S-(CH2)nCH3, - (CH2)m-NH-(CH2)nCH3, -C2-C8 alkenyl-0-(CH2)nCH3, -C2-C8 alkenyl-S-(CH2)nCH3, -C2-C8 alkeny I-N-(CH2) nCH3, -C2-C8 alkynyl-0-(CH2)nCH3, -C2-C8 alkynyl-S-(CH2)nCH3, -C2-C8 alkynyl-N-(CH2)nCH3, -(CH2)m-OH, -(CH2)m-NH2, -(CH2)m-0-NH2, -(CH2)m-S-NH2, -NH(CH2)mCH3, -NH(CH2)mOCH3, -NH(CH2)mCHOH-COOH, -N(CH3)2, -(CH2)m(NH)CH2OH, -NHCOOH, -(CH2)mNHCOOH, -N02, -SCN, -S02alkyl, -B(OH)2, -(CH2)mN(CH3)-S02-NH3,-(CH1)m-NH-S02-NH2, -NHC(=S)CH3, og - NHNH2; Y er valgt fra gruppen bestående af H, =0, -OCO(C1-C20 alkyl) og -OH; Z er valgt fra gruppen bestående af H og metyl; m er et heltal mellem 0-20; n er et heltal mellem 0-8; hvert - - - - symbol repræsenterer uafhængigt enten en enkeltbinding eller en dobbeltbinding, som er i stand til at danne en ketogruppe ved position 3 eller 17; og wwv-symbolet repræsenterer enhver type binding uanset stereokemien; og de respektive enantiomere, andre stereokemiske isomere, hydrater, solvater, tauto-mere og farmaceutisk acceptable salts af disse forbindelser, til anvendelse ved forebyggelse af demyelinering og/eller forstærkning af remye-linering af en axon af en nervecelle i et subjekt.
2. 6-substiteret estradiolderivat til anvendelse ved forebyggelse af demyelinering og/eller forstærkning af remyelinering af en axon af en nervecelle i et subjekt ifølge krav 1, hvori "a"-ringen er
Y er -OH; Z er metyl; Ru er H; R4 er valgt fra gruppen bestående af H, halogen og C^Ce alkyl; Ri og R2 er uafhængigt valgt fra gruppen bestående af H, -OH og halogen; R3 er valgt fra gruppen bestående af H, halogen og -OH; m er et heltal fra 1 -12; og n er et heltal fra 0-4.
3.
6-substiteret estradiolderivat til anvendelse ved forebyggelse af demyelinering og/eller forstærkning af remyelinering af en axon af en nervecelle i et subjekt ifølge krav 2, hvori X er valgt fra gruppen bestående af Ci-Ci2 alkyl, C2-C12 alkenyl, -(CH2)m-0-CH3, -(CH2)m-(CH2)nCH3, (CH2)m-S-CH3, og -(CH2)m-S-(CH2)nCH3.
4.
6-substiteret estradiolderivat til anvendelse ved forebyggelse af demyelinering og/eller forstærkning af remyelinering af en axon af en nervecelle i et subjekt ifølge krav 1, hvori forbindelsen er valgt fra gruppen bestående af {6S,8R,9S^ 3S, 14S)-3-hydroxy-6-(metoxymetyl)-13-mety 1-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]fenantren-17(14/-/)-on; (6fl,8F?,9S,13S, 14 S)-3-hydroxy-6-(metoxy mety I)-13-mety I-7,8,9,11,12,13,15,16-octahydro-6/-/-cyclopenta[a]fenantren-17(14/-/)-on; (6S,8R,9S,13 S, 14S)-6-( metoxy metyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[ a] tenant ren-3,17-diol; (6f?,8f?,9S,13S, 14 S)-6-(metoxy metyl)-13-metyl-7,8,9,11,12,13,14,15,1 6,17- decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (6S,87?,9S,107?,13S,14S)-17-hydroxy-6-(metoxymetyl)-10,13-dimetyl- 6.7.8.9.10.11.12.13.14.15.16.17- dodecahydro-37/-cyclopenta[a] tenant ren-3-on; (67?,87?,9S,107?,13S,14S)-17-hydroxy-6-(metoxymetyl)-10,13-dimetyl- 6.7.8.9.10.11.12.13.14.15.16.17- dodecahydro-37/-cyclopenta[a] tenant ren-3-on; (6S,87?,9S,13S,14S)-6-(hydroxymetyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6W-cyclopenta[a]fenantren-3,17-diol; (6 /=?, 8 7?, 9 S, 13 S, 1 4 S)-6-(hydroxy metyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6/-/-cyclopenta[a]fenantren-3,17-diol; (67?,87?,9S,107?,1 3S,14S)-6-(metoxymetyl)-10,13-dimetylhexadecahydro-1 7/-cyclopenta[a]fenantren-3,17-diol; (6 7?, 8 7?, 9 S, 13 S, 14 S)- 6-((am inooxy) metyl) -13-mety 1-7,8,9,11,12,13,14,15,16,17-decahydro-67/-cyclopenta[ a]fenantren-3,17-diol; (6S,87?,9S,13S,14S)-6-((aminooxy)metyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (67?,87?,9S,13S,14S)-6-((aminooxy)metyl)-17-hydroxy-13-metyl- 6.7.8.9.10.11.12.13.14.15.16.17- dodecahydro-3 7/-cyclopenta[a] tenant ren-3-on; (6S,87?,9S,13S, 14S)-6-((aminooxy)metyl)-17-hydroxy-13-metyl- 6.7.8.9.10.11.12.13.14.15.16.17- dodecahydro-37/-cyclopenta[a]fenantren-3-on; (6 7?, 87?, 9 S, 13 S, 14S)-6-(((metoxymetyl)amino)metyl)-13-metyl- 7.8.9.11.12.13.14.15.16.17- decahydro-67V-cyclopenta[a]fenantren-3,17-diol; (6S,87?,9S,13S,14S)-6-(((metoxymetyl)amino)metyl)-13-metyl- 7.8.9.11.12.13.14.15.16.17- decahydro-67/-cyclopenta[a]fenantren-3,17-diol; 1 -((((67?,87?,9S,13S,14S)-3,17-dihydroxy-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-6-yl)metyl)amino)propan-2-on; 1 - ((((6S,87?,9S,13S,14S)-3,17-dihydroxy-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-67/-cyclopenta[a]fenantren-6-yl)metyl)amino)propan-2-on; (67?,87?,9S,13S,14S)-6-metoxy-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-677-cyclopenta[a]fenantren-3,17-diol; (6S,87?,9S,13S, 14S)-6-(2-metoxyetyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-67/-cyclopenta[a]fenantren-3,17-diol; (67?,87?,9S,13S,14S-6-(4-metoxybutyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-67/-cyclopenta[a]fenantren-3,17-diol; (67?,87?,9S,13S, 14 S)-6-(6-metoxy hexyl)-13-mety 1-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,13S, 14S)-6-(6-metoxyoctyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,13S,14S)-3-hydroxy-6-(metoxymetyl)-l3-metyl- 7.8.9.11.12.13.14.15.16.17- decahydro-6H-cyclopenta[a]fenantren-17-yl stearat; (6R,8R,9S,10R,13S,14S)-6-(metoxymetyl)-10,13-dimetyl- 7.8.9.10.11.12.13.14.15.16- decahydro-3H-cyclopenta[a]fenantren-3,17(6H)-dion; (6S,8R,9S,10R,13S,14S)-6-(metoxymetyl)-10,13-dimetyl- 7.8.9.10.11.12.13.14.15.16- decahydro-3/-/-cyclopenta[ a]fenantren-3,17(6H-dion; (6R,8R,9S,10R,13S,14S)-6-(metoxymetyl)-10,13-dimetyl- 4.5.6.7.8.9.10.11.12.13.14.15.16.17- tet radecahydro-3H-cyclopenta[a]fenantren- 3.17- diol; (6S,8R,9S,10R,3S,14S)-6-(metoxymetyl)-10,13-dimetyl- 4.5.6.7.8.9.10.11.12.13.14.15.16.17- tetradecahydro-3H-cyclopenta[ ajfenantren- 3.17- diol; (6S,8R,9S13S,14S)-6-(metoxymetyl)-13-metyl-17-oxo- 7.8.9.11.12.13.14.15.16.17- decahydro-6H-cyclopenta[a]fenantren-3-y I hydrogensulfat; (6fl,8R,9S,13S,14S)-6-(metoxymetyl)-13-metyl-17-oxo- 7.8.9.11.12.13.14.15.16.17- decahydro-6H-cyclopenta[a]fenantren-3-yl hydrogensulfat; (6R,8R,9S,13S,14S)-13-metyl-6-(4-propoxybutyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6/-/-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,13 S, 1 4S)-13-metyl-6-(5-ethoxy penty I)-7,8,9,11,12,13,14,15,16,17-decahydro-6/-/-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,1 OR, 13S,14S)-6-(metoxymetyl)-10,13-dimetylhexadecahydro-1 H-cyclopenta[a]fenantren-3,17-diol; og (6R,8S,9S, 14S, 1 7 S)-6-(metoxymetyl)-7,8,9,11,12,13,14,1 5,16,17-decahydro-6 R-cyclopenta[a]fenantren-3,17-diol.
5.
6-substiteret estradiolderivat til anvendelse ved forebyggelse af demyelinering og/eller forstærkning af remyelinering af en axon af en nervecelle i et subjekt ifølge krav 4, hvori forbindelsen er valgt fra gruppen bestående af (6R,8R,9S,13S,14S)-6-(metoxymetyl)-13-metyl-7,8,9,11,12,13,14,15,1 6,17-decahydro-6H-cyclopenta[a]fenantren-3,7-diol og (6R,8R,9S,13S,14S)-6-(6- m etoxy hexy I) -13-mety 1-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol. 6. 6-substitueret estradiolderivat med formlen:
hvori "a"-ringen er valgt fra gruppen bestående af
Ri, R2, R3 og R4 er uafhængigt valgt fra gruppen bestående af H, Ci-C6 alkyl, halogen, et sulfat, et glucuronid, -OH, en sterisk krævende gruppe, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, -N(CH2)n, en fosfatgruppe og en fosfinatgruppe; Ru er valgt fra gruppen bestående af Η, CrCs alkyl, halogen, et sulfat, et gluco-ronid, -S02NH2, -COOH, -CN, -CH2CN-, -NHCN-, -CHO, =CHOCH3,-COO salt, -0S02alkyl, -NH2, og -NHCO(CH2)n; X er valgt fra gruppen bestående af (VC^ alkyl, C2-C12 alkenyl, C2-C12 alkynyl, halogen, et glucoronid, -NH2, -S02NH2, -COOH, -CN, -CH2CN, -NHCN, -CHO, -COOsalt, -0S02alkyl, -SH, -SCH3, -CH[(CH2)nCH3]COOCH3, -(CH2)mCOOCH3, -(CH2)m-0-CH3, -(CH2)m-0-(CH2)nCH3, (CH2)m-S-CH3, -(CH2)m-S-(CH2)nCH3, - (CH2)m-NH-(CH2)nCH3, -C2-C8 alkenyl-0-(CH2)nCH3, -C2-C8 alkenyl-S-(CH2)nCH3, -C2-C8 alkenyl-N-(CH2)nCH3, -C2-C8 alkynyl-0-(CH2)nCH3, -C2-C8 alkynyl-S-(CH2)nCH3, -C2-C8 alkynyl-N-(CH2)nCH3, -(CH2)m-OH, -(CH2)m-NH2, -(CH2)m-0-NH2, -(CH2)m-S-NH2, -NH(CH2)mCH3, -NH(CH2)mOCH3, -NH(CH2)mCHOH-COOH, -N(CH3)2, -(CH2)m(NH)CH2OH, -NHCOOH, -(CH2)mNHCOOH, -N02, -SCN, -S02alkyl, -B(OH)2, -(CH2)m N(CH3)-S02-NH3,-(CH2)m-NH-S02-NH2, -NHC(=S)CH3, og -NHNH2; Y er valgt fra gruppen bestående af H, =0, -OCO(Ci-C20 alkyl) og -OH; Z er valgt fra gruppen bestående af H og metyl; m er et heltal mellem 0-20; n er et heltal mellem 0-8; hvert - - - - symbol repræsenterer uafhængigt enten en enkeltbinding eller en dobbeltbinding, som er i stand til at danne en ketogruppe ved position 3 eller 17; og _»wvvv-symbolet repræsenterer enhver type binding uanset stereokemien; og de respektive enantiomere, andre stereokemiske isomere, hydrater, solvater, tauto-mere og farmaceutisk acceptable salts af disse forbindelser; til anvendelse ved behandling af en demyelineringslidelse. 7. 6-substiteret estradiolderivat til anvendelse ved behandling af en demyelineringslidelse ifølge krav 6, hvori "a"-ringen er
Y er -OH; Z er metyl; R11 er H; R4 er valgt fra gruppen bestående af H, halogen og (VCe alkyl; Ri og R2 er uafhængigt valgt fra gruppen bestående af H, -OH og halogen; R3 er valgt fra gruppen bestående af H, halogen og -OH; m er et heltal fra 1-12; og n er et heltal fra 0-4.
8.
6-substiteret estradiolderivat til anvendelse ved behandling af en demyelineringslidelse ifølge krav 7, hvori X er valgt fra gruppen bestående af CrC12 alkyl, C2-C12 alkenyl, -(CH2)m-0-CH3, -(CH2)m-0-(CH2)nCH3, (CH2)m-S-CH3, og -(CH2)m-S-(CH2)nCH3.
9.
6-substiteret estradiolderivat til anvendelse ved behandling af en demyelineringslidelse ifølge krav 6, hvori forbindelsen er valgt fra gruppen bestående af (6S,8R,9S, 13S, 1 4S)-3-hydroxy-6-(metoxymetyl)-13-metyl-7,8,9,11,12,13,15,16-octahydro-6/-/-cyclopenta[a]fenantren-17(14/-/)-on; (6 77,8 R, 9 S, 13 S, 14 S)-3-hydroxy-6-(met oxy metyl)-13-metyl-7,8,9,11,12,13,15,16-octahydro-6 H-cyclopenta[a] tenant ren-17(14 H)-on; (6S,8F?,9S, 13S, 1 4S)-6-(metoxymetyl)-13-metyl-7,8,9,11,12,13,14,15,1 6,1 7-decahydro-6/-/-cyclopenta[a]fenantren-3,17-diol; (θβ,δβ,θδ, 13S, 14S)-6-(metOxymetyl)-13-metyl-7,8,9,11,12,13,14,1 5,1 6,17-decahydro-6/-/-cyclopenta[a]fenantren-3,17-diol; (6S,8F?,9S, 1 OR, 1 3 S, 14 S)-17-hydroxy-6-(m etoxymetyl)-1 0,13-dimetyl- 6,7,8,9,10,11,12,13,14,15,16,1 7-dodecahydro-3/-/-cyclopenta[a] tenant ren-3-on; (6R,8R,9S,10R,1 3S,14S)-1 7-hydroxy-6-(metoxymetyl)-1 0,13-dimetyl- 6,7,8,9,10,11,12,13,14,1 5,1 6,17-dodecahydro-3/-/-cyclopenta[a]fenantren-3-on; (6S,8R,9S, 13 S, 1 4S)-6-(hydroxymetyl)-13-metyl-7,8,9,11,12,13,14,1 5,1 6,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9 S, 13 S, 14 S) -6-(hydroxy metyl) -13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6A7-cyclopenta[ a]fenantren-3,17-diol; (6 R, 8 H 9 S, 1 Øfl,13S,14S)-6-(metoxymetyl)-10,13-dimetylhexadecahydro-1 H-cyclopenta[a]fenantren-3,17-diol; (6fi,8R,9S,13S,1 4S)-6-((aminooxy)metyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (6 S, 8 R, 9 S, 13 S, 14S)-6-((aminooxy)metyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6R-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,13S, 14S)-6-((aminooxy)metyl)-1 7-hydroxy-13-metyl- 6.7.8.9.10.11.12.13.14.15.16.17- dodecahydro-3/-/-cyclopenta[a]fenantren-3-on; (6S,8R,9S, 13S,14S)-6-((aminooxy)metyl)-17-hydroxy-13-metyl- 6.7.8.9.10.11.12.13.14.15.16.17- dodecahydro-3/-/-cyclopenta[a]fenantren-3-on; (6R,8R,9S,13S,14 S) -6-((( metoxy metyl) amino) metyl)- 13-metyl- 7.8.9.11.12.13.14.15.16.17- decahydro-6R-cyclopenta[a] tenant ren-3,17-diol; (6S,8R,9S,13S,14S)-6-(((metoxymetyl)amino)metyl)-13-metyl- 7.8.9.11.12.13.14.15.16.17- decahydro-6/-/-cyclopenta[a]fenantren-3,17-diol; 1-((((6R,8R,9S,13S,14S)-3,17-dihydroxy-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-6-yl)metyl)amino)propan-2-on; 1 - ((((6S,8R,9S,13S,14S)-3,17-dihydroxy-13-mety 1-7,8,9,11,12,13,14,15,16,17-decahydro-6R-cyclopenta[a]fenantren-6-yl)metyl)amino)propan-2-on; (6R,8R,9S,13S, 14 S)-6-metoxy-13-mety 1-7,8,9,11,12,13,14,15,16,17-decahydro-6R-cyclopenta[a]fenantren-3,17-diol; (6S,8R,9S, 13 S, 14S)-6-(2-metoxy ety I)-13-mety 1-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,13S,14S)-6-(4-metoxybutyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,13S,14S)-6-(6-metoxyhexyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6R-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,13 S, 14S)-6-(6-metoxyocty I)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,13S,14S)-3-hydroxy-6-(metoxymetyl)-13-metyl- 7.8.9.11.12.13.14.15.16.17- decahydro-6H-cyclopenta[a]fenantren-17-yl stearat; (6R,8R,9S,10R,13S,14S)-6-(metoxymetyl)-10,13-dimetyl- 7,8,9,10,11,12,13,14,15,16-decahydro-3 R-cyclopenta[a] tenant ren-3,17(6/-/)- dion; (6S,8R,9S, 1 OR, 13S, 14S)-6-(metoxymetyl)-10,13-dimetyl- 7,8,9,10,11,12,1 3,14,1 5,1 6-decahydro-3R-cyclopenta[a]fenantren-3,17(6H)- dion; (6R8R9S, 10R, 1 3S, 14S)-6-(metoxym etyl)-10,13-dim etyl- 4.5.6.7.8.9.10.11.12.13.14.15.16.17- tetradecahydro-3/-/-cyclopenta[ a] fenantren- 3.17- diol; (6S,8R,9S, 10R, 13 S, 14S)-6-(metoxymetyl)-1 0,13-dimetyl- 4.5.6.7.8.9.10.11.12.13.14.15.16.17- tetradecahydro-3H-cyclopenta[a]fenantren- 3.17- diol; (6S,8R,9S, 13 S, 1 4S)-6-(m etoxy metyl)-13-metyl-17-oxo- 7.8.9.11.12.13.14.15.16.17- decahydro-6R-cyclopenta[a]fenantren-3-yl hydrogensulfat; (6R,8R,9S,13S,14S)-6-(metoxymetyl)-13-metyl-17-oxo- 7.8.9.11.12.13.14.15.16.17- decahydro-6R-cyclopenta[a]fenantren-3-yl hydrogensulfat; (6R,8R,9S,13S,14S)-13-metyl-6-(4-propoxybutyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,13S, 14S)-13-metyl-6-(5-ethoxypentyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6R-cyclopenta[a]fenantren-3,17-diol; (6R,8R,9S,10R,13S,14S)-6-(metoxymetyl)-10,13-dimetylhexadecahydro-1 H-cyclopenta[a]fenantren-3,17-diol; og (6R,8S,9S, 14 S, 1 7S)-6-(metoxymetyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6R-cyclopenta[a]fenantren-3,17-diol.
10.
6-substiteret estradiolderivat til anvendelse ved behandling af en demyeline-ringslidelse ifølge krav 9, hvori forbindelsen er valgt fra gruppen bestående af (6R8R9S, 13S, 14S)-6-(metoxymetyl)-13-metyl-7,8,9,11,12,13,14,1 5,1 6,17-decahydro-6R-cyclopenta[a]fenantren-3,17-diol og (6R,8R,9S,13S,14S)-6-(6-metoxyhexyl)-13-metyl-7,8,9,11,12,13,14,15,16,17-decahydro-6R-cyclopenta[a]fenantren-3,17-diol. 11. 6-substiteret estradiolderivat til anvendelse ved behandling af en demyeline-ringslidelse ifølge krav 10, hvori forbindelsen er valgt fra gruppen bestående af dissemineret sklerose, central pontin myelinolyse, empirisk autoimmun encephalomyelitis, akut dissemineret encephalomyelitis, tværgående myelitis, progressiv multifokal leukoencefalopati; Alzheimers sygdom, subakut sklerosisk panen-cephalitis, post-infektiøs encephalomyelitis, kronisk inflammatorisk demyelineren- de polyneuropati, progressiv supernuklear lammelse, multifokal motorisk neuropath Guillain-Barre Syndrom, progressiv multifokal leukoencefalopati, Devics sygdom, Balos koncentriske sklerose, Krabbe sygdom, adrenoleukodystrofi (ALD), Pelizaeus-Merzbacher sygdom, Canavan sygdom, barndomsataksi med central hypomyelinering, Alexanders sygdom, Cockayne syndrom, Van der Knapp syndrom, Zellweger syndrom og Refsums sygdom. 12. 6-substiteret estradiolderivat til anvendelse ved behandling af en demyeline-ringslidelse ifølge krav 11, hvori lidelsen er dissemineret sklerose. 13. 6-substiteret estradiolderivat til anvendelse ved behandling af en demyeline-ringslidelse ifølge krav 12, hvori remyelineringen overvåges ved en forbedring af et symptom på en demyelineringslidelse. 14. 6-substiteret estradiolderivat til anvendelse ved behandling af en demyelineringslidelse ifølge krav 13, hvori forbindelsen gives i kombination med et antiin-flammatorisk middel eller en immunmodulator.
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