DK2882428T3 - Fremgangsmåde til at inhibere tau-phosphorylering - Google Patents
Fremgangsmåde til at inhibere tau-phosphorylering Download PDFInfo
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- DK2882428T3 DK2882428T3 DK13816713.5T DK13816713T DK2882428T3 DK 2882428 T3 DK2882428 T3 DK 2882428T3 DK 13816713 T DK13816713 T DK 13816713T DK 2882428 T3 DK2882428 T3 DK 2882428T3
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Claims (11)
1. Forbindelse af serie C-2 eller et farmaceutisk acceptabelt salt deraf der inhiberer mindst 60 procent af den FITC-mærkede naloxonbinding når den er til stede i en 10 μΜ koncentration og under anvendelse af umærket naloxon som kontrolinhibitoren i den samme koncentration, til anvendelse til at inhibere phosphorylering af tau-proteinet i en fremgangsmåde til behandling af kronisk traumatisk encefalopati, hvor fremgangsmåden omfatter indgivelse af forbindelsen eller det farmaceutisk acceptable salt deraf i fraværet af en effektiv mængde afen mu opioid receptor- (MOR-) binding afen separat MOR-agonist eller -antagonist, og hvor forbindelsen af serie C-2 er beskrevet med formlen I nedenfor:
hvor Q er CHR9 eller C(O), Z er CHR10 eller C(O), og kun en af Q og Z er C(O); hver af m, n og p er nul eller en, og summen af m+n + p er 2 eller 3; W er valgt fra gruppen bestående af NR20, NR2, NR7, S og O, hvor R7 og R2 er de samme eller forskellige og er H, C(H)v(D)h, hvor hver af v og h er 0, 1, 2 eller 3 og v+h = 3, C(H)q(D)r-alifatisk Ci-Cn-hydrocarbyl, hvor hver af q og r er 0, 1, eller 2 og q + r = 0, 1 eller 2, alifatisk C1-C12-hydrocarbylsulfonyl eller alifatisk Ci-Ci2-hydrocarboyl, og R20 er X-cirkel A-R1 som defineret i det følgende; J og Fer de samme eller forskellige og er CH2, CHD eller CD2 (hvor D er deuterium) X er SO2, C(O), CH2, CD2, OC(O), NHC(NH), NHC(S) eller NHC(O); cirkel A er et aromatisk eller heteroaromatisk ringsystem der indeholder en enkelt ring eller to fusionerede ringe;
R1 er H eller repræsenterer op til tre substituenter, Rla, Rlb, og Rlc, der selv kan være de samme eller forskellige, hvor hver af disse tre grupper, Rla_c, er valgt separat fra gruppen bestående af H, Ci-Ce-hydrocarbyl, Ci-Ce-hydrocarbyloxy, Ci-Ce-hydrocarbyloxycarbonyl, trifluormethyl, trifluormethoxy, C1-C7 hydrocarboyl, hydroxy-, trifluormethyl- eller halogen-substitueret Ci-Cyhydrocarboyl, Ci-Ce-hydrocarbylsulfonyl, Ci-Ce-hydrocarbyloxysulfonyl, halogen, nitro, phenyl, cyano, carboxyl, C1-C7-hydrocarbylcarboxylat, carboxamid eller sulfonamid, hvor amidonitrogenet i hvilken som helst amidgruppe har formlen NR3R4, hvor R3 og R4 er de samme eller forskellige og er H, Ci-C4-hydrocarbyl, eller R3 og R4 sammen med det viste nitrogen danner en 5-7-leddet ring, der eventuelt indeholder 1 eller 2 yderligere heteroatomer, der uafhængigt er nitrogen, oxygen eller svovl, MAr, hvor M er -CH2-, -O- eller -N = N- og Ar er en aryl- eller heteroarylgruppe med en enkelt ring og NR5R6, hvor R5 og R6 er de samme eller forskellige og er H, Ci-C4-hydrocarbyl, Ci-C4-acyl, C1-C4-hydrocarbylsulfonyl, eller R5 og R6 sammen med det viste nitrogen danner en 5-7-leddet ring, der eventuelt indeholder 1 eller 2 yderligere heteroatomer, der uafhængigt er nitrogen, oxygen eller svovl. R8, R9 og R10 er hver H, eller to af R8, R9 og R10 er H, og en er en Ci-Cs-hydrocarbylgruppe, der er ikke-substitueret eller substitueret med op til tre atomer, der er de samme eller forskellige og er oxygen- eller nitrogenatomer.
2. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge krav 1, hvor forbindelsen udviser mindre end 80 procent af MOR-stimuleringen tilvejebragt med DAMGO i den samme koncentration.
3. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge krav 1, hvor forbindelsen er en forbindelse af serie C-2 der har den samme struktur som formlen II nedenfor:
hvor J og F er de samme eller forskellige og er CH2, CHD eller CD2 (hvor D er deuterium).
4. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge krav 1, hvor forbindelsen er en forbindelse af serie C-2 der har den samme struktur som formlen III nedenfor:
hvor J og F er de samme eller forskellige og er CH2, CHD eller CD2 (hvor D er deuterium); og hver af m og n er en.
5. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge krav 1, hvor forbindelsen er en forbindelse af serie C-2 der har den samme struktur som en forbindelse valgt fra gruppen bestående af:
6. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge et hvilket som helst af kravene 1-5, hvor fremgangsmåden omfatter indgivelse af forbindelsen eller det farmaceutisk acceptable salt deraf flere gange.
7. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge et hvilket som helst af kravene 1-5, hvor fremgangsmåden omfatter indgivelse af forbindelsen eller det farmaceutisk acceptable salt deraf dagligt.
8. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge et hvilket som helst af kravene 1-5, hvor fremgangsmåden omfatter indgivelse af forbindelsen eller det farmaceutisk acceptable salt deraf flere gange dagligt.
9. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge et hvilket som helst af kravene 1-5, hvor forbindelsen eller det farmaceutisk acceptable salt af forbindelsen indgives i en farmaceutisk sammensætning.
10. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge krav 9, hvor den farmaceutiske sammensætning er i flydende form.
11. Forbindelse eller farmaceutisk acceptabelt salt deraf til anvendelse ifølge krav 9, hvor den farmaceutiske sammensætning er i fast form.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US201261671235P | 2012-07-13 | 2012-07-13 | |
US201361789180P | 2013-03-15 | 2013-03-15 | |
PCT/US2013/050126 WO2014011917A2 (en) | 2012-07-13 | 2013-07-11 | A method of inhibiting tau phosphorylation |
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DK2882428T3 true DK2882428T3 (da) | 2019-04-15 |
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WO2020168096A1 (en) * | 2019-02-13 | 2020-08-20 | Yale University | Methods of treating epilepsy |
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WO2022098700A1 (en) * | 2020-11-03 | 2022-05-12 | Cassava Sciences, Inc. | Inhibiting an immune response mediated by one or more of tlr2, rage, ccr5, cxcr4 and cd4 |
CN114252324B (zh) * | 2022-03-02 | 2022-05-13 | 中国人民解放军军事科学院军事医学研究院 | 一种方便使用的多孔脑片孵育装置 |
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2013
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- 2013-07-11 JP JP2015521820A patent/JP6417324B2/ja active Active
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JP6630374B2 (ja) | 2020-01-15 |
ES2716049T3 (es) | 2019-06-07 |
US20240117306A1 (en) | 2024-04-11 |
EP2882428A4 (en) | 2016-09-14 |
US11661580B2 (en) | 2023-05-30 |
JP6417324B2 (ja) | 2018-11-07 |
JP7419486B2 (ja) | 2024-01-22 |
US10760052B2 (en) | 2020-09-01 |
JP2019031520A (ja) | 2019-02-28 |
US20210095248A1 (en) | 2021-04-01 |
JP2023036695A (ja) | 2023-03-14 |
WO2014011917A2 (en) | 2014-01-16 |
EP2882428B1 (en) | 2019-01-16 |
US20140018341A1 (en) | 2014-01-16 |
JP2015523385A (ja) | 2015-08-13 |
US10017736B2 (en) | 2018-07-10 |
JP2018095648A (ja) | 2018-06-21 |
US20190136184A1 (en) | 2019-05-09 |
JP2022000421A (ja) | 2022-01-04 |
US20210389298A1 (en) | 2021-12-16 |
EP2882428A2 (en) | 2015-06-17 |
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