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DK3166925T3 - Isoindolinderivater til anvendelse i behandlingen af en viral infektion. - Google Patents

Isoindolinderivater til anvendelse i behandlingen af en viral infektion. Download PDF

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Publication number
DK3166925T3
DK3166925T3 DK15742106.6T DK15742106T DK3166925T3 DK 3166925 T3 DK3166925 T3 DK 3166925T3 DK 15742106 T DK15742106 T DK 15742106T DK 3166925 T3 DK3166925 T3 DK 3166925T3
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tert
lcms
butoxv
nmr
acetic acid
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DK15742106.6T
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Brian Alvin Johns
Emile Johann Velthuisen
Lita Suwandi
David Temelkoff
Jason Gordon Weatherhead
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Viiv Healthcare Uk Ltd
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    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • A—HUMAN NECESSITIES
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
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    • A61P31/18—Antivirals for RNA viruses for HIV
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    • C07D407/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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Claims (16)

1. Forbindelse ifolge formel I:
Formel I hvor: R1 er Ci-6alkyl; R2 er C5-i4aryl, C3-7cycloalkyl, C3-7cycloalkenyl, C2-9heterocyklus, eller C2-9heteroaryl, hvor hver R2 gruppe eventuelt er substitueret med en til fire substituenter valgt blandt halo, Ci-6alkyl, Ci-6hetereoalkyl eller Ci-6alkylen eller Ci-6hetereoalklylen, hvor Ci-6alkylenen eller Ci-6hetereoalklylenen er bundet til tilstodende carbonatomer pa Cs-^arylen, C3-7cycloalkylen, C3-7cycloalkenylen, Ci-gheterocyklen eller Cs-gheteroarylen, for at danne en kondenseret ring; L er en binding, -CFhCCO)-, -Ci-3alkylen-, -SO2-, -C(O)-, -C(S)-, -C(NFI)-, -C(0)NH-,-C(0)NHCH2-,-C(0)N-, -C(0)0CH2-, -C(0)0-, -C(0)C(0)-, -SO2-NH- eller -CH2C(0)-; R3 er H, CN, Ci-6alkyl, C5-i4aryl, CFhCs-waryl, CFl2C3-7cycloalkyl, C3-7cycloalkyl, C3-7spirocycloalkyl, C3-7cycloalkenyl, C2-gheterocyklus eller C2-gheteroaryl, hvor hver R3-gruppe eventuelt er substitueret med en til fire substituenter valgt blandt halo, Ci-6alkyl, C2-sbrokoblet-heterocyklus, C3-7cycloalkyl, Ci-3fluoroalkyl, -OCi-6alkyl, -C(0)R4, -C(0)NR4, -C(0)NHR4, C5-i4aryl, Ci-6hetereoalkyl, -B(OFI)2, C2-gheterocyklus, Ci-6heteroaryl, -C(0)0Ci-6alkyl eller to substituenter bundet til tilstodende atomer kan hinde sammen for at danne en kondenseret ring og den kondenserede ring kan eventuelt vaere substitueret med R4; R4 er CN, halo, -OCi-6alkyl, Ci-6alkyl, C3-7cycloalkyl, C2-gheterocyklus eller C5-i4aryl; og hvor hver heterocyklus, heteroaryl, heteroalkyl og heteroalkylen omfatter en til tre heteroatomer valgt blandt S, N, B eller O.
2. Forbindelse ifolge krav 1, hvor R1 ert-butyl.
3. Forbindelse ifolge et hvilket som helst af krav 1-2, hvor R2 eventuelt er substitueret phenyl.
4. Forbindelse ifolge krav 3, hvor R2 er phenyl substitueret med en til fire substituenter valgt blandt fluor, methyl, -CFI2CFI2CFI2O-, hvor naevnte -CFI2CFI2CFI2O- er bundet til tilstodende carbonatomer pa phenylen for at danne en bicyklisk ring, eller -NFICFI2CFI2O- hvor naevnte -NFICFI2CFI2O- er bundet til tilstodende carbonatomer pa phenylen for at danne en bicyklisk ring.
5. Forbindelse ifolge et hvilket som helst af krav 1-4, hvor R3 er Ci-6alkyl, phenyl, naphthyl, cyclopentyl, cyclohexyl, pyridyl eller tetrahydropyranyl, som hver isaer eventuelt er substitueret med 1-3 substituenter valgt blandt halogen, Ci-6alkyl, -OCi-6alky, Ci- 3fluoroalkyl eller phenyl.
6. Forbindelse ifolge et hvilket som helst af krav 1-5, hvor stereokemien pa kulstoffet hvor OR1 er bundet er som vist nedenfor
7. Forbindelse ifolge krav 1, hvor forbindelsen er
8. Forbindelse ifolge krav 1, hvor forbindelsen er
9. Forbindelse ifolge krav 1, hvor forbindelsen er
10. Et farmaceutisk acceptabelt salt af en forbindelse ifolge et hvilket som helst af krav 1-9.
11. Farmaceutisk sammensaetning omfattende en forbindelse eller salt ifolge et hvilket som helst af krav 1-10.
12. Farmaceutisk sammensaetning ifolge krav 11 til anvendelse i behandling af en viral infektion hos en patient medieret mindst delvist af en virus fra retrovirusfamilien.
13. Farmaceutisk sammensaetning til anvendelse ifolge krav 12, hvor den virale infektion er medieret af FlIV-virusen.
14. Forbindelse eller salt som defineret i et hvilket som helst af krav 1-10 til anvendelse i medicinsk terapi.
15. Forbindelse eller salt som defineret i et hvilket som helst af krav 1-10 til anvendelse i behandling af en viral infektion hos et menneske.
16. Anvendelse af en forbindelse eller salt som defineret i et hvilket som helst af krav 1-10 til fremstilling af et laegemiddel til anvendelse i behandling af en viral infektion hos et menneske.
DK15742106.6T 2014-07-08 2015-07-06 Isoindolinderivater til anvendelse i behandlingen af en viral infektion. DK3166925T3 (da)

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US201462021844P 2014-07-08 2014-07-08
US201462064615P 2014-10-16 2014-10-16
US201562134616P 2015-03-18 2015-03-18
PCT/IB2015/055095 WO2016005878A1 (en) 2014-07-08 2015-07-06 Isoindoline derivatives for use in the treatment of a viral infection

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US9975906B2 (en) 2014-05-16 2018-05-22 Shionogi & Co., Ltd. Tricyclic heterocycle derivatives having HIV replication inhibitory effect
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