DE15187654T1 - Antivirales Mittel - Google Patents

Antivirales Mittel Download PDF

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Publication number
DE15187654T1
DE15187654T1 DE15187654.7T DE15187654T DE15187654T1 DE 15187654 T1 DE15187654 T1 DE 15187654T1 DE 15187654 T DE15187654 T DE 15187654T DE 15187654 T1 DE15187654 T1 DE 15187654T1
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Germany
Prior art keywords
optionally substituted
ring
solvate
pharmaceutically acceptable
acceptable salt
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DE15187654.7T
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English (en)
Inventor
Yasuhiko Kanda
Takashi Kawasuji
Toshio Fujishita
Shozo Takechi
Yukio Tada
Ryuichi Kiyama
Masahiro Fuji
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Shionogi and Co Ltd
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Shionogi and Co Ltd
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27347328&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DE15187654(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Shionogi and Co Ltd filed Critical Shionogi and Co Ltd
Publication of DE15187654T1 publication Critical patent/DE15187654T1/de
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic 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
    • A61K31/4025Heterocyclic 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 not condensed and containing further heterocyclic rings, e.g. cromakalim
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    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4151,2-Diazoles
    • A61K31/41551,2-Diazoles non condensed and containing further heterocyclic rings
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    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
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    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non 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
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    • A61K31/47Quinolines; Isoquinolines
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    • A61K31/513Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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Abstract

Verbindung der Formel (I):wobei RC und RD zusammen genommen mit den angrenzenden Kohlenstoffatomen einen Ring bilden, der kondensiert sein kann, Y Hydroxy ist; Z O ist; RA ein durch die Formeldargestellter Rest ist, wobei der Ring C ein aromatischer Heterocyclus ist, der N enthält, wobei mindestens ein Atom, angrenzend an das Atom an der Bindestelle, ein nicht substituiertes N-Atom ist; wobei die gestrichelte Linie die Anwesenheit oder Abwesenheit einer Bindung darstellt, oder ein durch die Formel ...

Claims (20)

  1. Verbindung der Formel (I):
    Figure DE000015187654T1_0003
    wobei RC und RD zusammen genommen mit den angrenzenden Kohlenstoffatomen einen Ring bilden, der kondensiert sein kann, Y Hydroxy ist; Z O ist; RA ein durch die Formel
    Figure DE000015187654T1_0004
    dargestellter Rest ist, wobei der Ring C ein aromatischer Heterocyclus ist, der N enthält, wobei mindestens ein Atom, angrenzend an das Atom an der Bindestelle, ein nicht substituiertes N-Atom ist; wobei die gestrichelte Linie die Anwesenheit oder Abwesenheit einer Bindung darstellt, oder ein durch die Formel
    Figure DE000015187654T1_0005
    dargestellter Rest ist, wobei X O ist; RB ein aus der Substitutionsgruppe A ausgewählter Substituent ist; mindestens eines von dem von RC und RD gebildeten Ring, Ring C und RB mit einem Rest -Z1-Z2-Z3-R1 substituiert ist, wobei Z1 und Z3 jeweils unabhängig eine Bindung, gegebenenfalls substituiertes Alkylen oder gegebenenfalls substituiertes Alkenylen sind; Z2 eine Bindung, gegebenenfalls substituiertes Alkylen, gegebenenfalls substituiertes Alkenylen, -CH(OH)-, -S-, -SO-, -SO2-, -SO2NR2-, -NR2SO2-, -O-, -NR2-, -NR2CO-, -CONR2-, -C(=O)-O-, -O-C(=O)- oder -CO- ist; R2 Wasserstoff, gegebenenfalls substituiertes Alkyl, gegebenenfalls substituiertes Alkenyl, gegebenenfalls substituiertes Aryl oder gegebenenfalls substituiertes Heteroaryl ist; R1 gegebenenfalls substituiertes Aryl, gegebenenfalls substituiertes Heteroaryl, gegebenenfalls substituiertes Cycloalkyl, gegebenenfalls substituiertes Cycloalkenyl oder gegebenenfalls substituierter Heterocyclus ist, wobei der von RC und RD gebildete Ring, der Ring C oder RB gegebenenfalls mit einem nicht interferierenden Substituenten substituiert ist an einer Position, an der sich der Rest -Z1-Z2-Z3-R1 nicht befindet (wobei Z1, Z2, Z3 und R1 wie vorstehend definiert sind); die Substitutionsgruppe A aus Alkyl, Alkoxy, Hydroxy, gegebenenfalls substituiertem Amino, gegebenenfalls substituiertem Cycloalkyl, gegebenenfalls substituiertem Cycloalkenyl, gegebenenfalls substituiertem Heterocyclus, gegebenenfalls substituiertem Aryl oder gegebenenfalls substituiertem Heteroaryl besteht, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  2. Verbindung nach Anspruch 1, wobei der von RC und RD gebildete Ring ein 5- bis 6-gliedriger Ring ist, der (ein) Heteroatom(e) enthalten kann und damit kondensiert sein kann, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  3. Verbindung nach Anspruch 2, wobei der von RC und RD gebildete Ring ein 5- bis 6-gliedriger Ring ist, der (ein) Heteroatom(e) O und/oder N enthalten kann und mit einem Benzolring kondensiert ist, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  4. Verbindung nach Anspruch 3, wobei der von RC und RD gebildete Ring ein 6-gliedriger Ring ist, der (ein) Heteroatom(e) N enthält und mit einem Benzolring kondensiert ist, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  5. Verbindung nach Anspruch 3, wobei der von RC und RD gebildete Ring ein 6-gliedriger Ring ist, der (ein) Heteroatom(e) N enthält, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  6. Verbindung nach einem der Ansprüche 1 bis 5, wobei die nicht interferierenden Substituenten unabhängig ausgewählt sind aus Wasserstoff, Halogen, Alkoxycarbonyl, Carboxy, Alkyl, Alkoxy, Alkoxyalkyl, Nitro, Hydroxy, Hydroxyalkyl, Alkenyl, Alkinyl, Alkylsufonyl, gegebenenfalls substituiertem Amino, Alkylthio, Alkylthioalkyl, Haloalkyl, Haloalkoxy, Haloalkoxyalkyl, gegebenenfalls substituiertem Cycloalkyl, gegebenenfalls substituiertem Cycloalkenyl, gegebenenfalls substituiertem Heterocyclus, Oxo, Thioxo, Nitroso, Azid, Amidino, Guanidino, Cyano, Isocyano, Mercapto, gegebenenfalls substituiertem Carbamoyl, Sulfamoyl, Sulfoamino, Formyl, Alkylcarbonyl, Alkylcarbonyloxy, Hydrazino, Morpholino, gegebenenfalls substituiertem Aryl, gegebenenfalls substituiertem Heteroaryl, gegebenenfalls substituiertem Aralkyl, gegebenenfalls substituiertem Heteroarylalkyl, gegebenenfalls substituiertem Aryloxy, gegebenenfalls substituiertem Heteroaryloxy, gegebenenfalls substituiertem Arylthio, gegebenenfalls substituiertem Heteroarylthio, gegebenenfalls substituiertem Aralkyloxy, gegebenenfalls substituiertem Heteroarylalkyloxy, gegebenenfalls substituiertem Aralkylthio, gegebenenfalls substituiertem Heteroarylalkylthio, gegebenenfalls substituiertem Aryloxyalkyl, gegebenenfalls substituiertem Heteroaryloxyalkyl, gegebenenfalls substituiertem Arylthioalkyl, gegebenenfalls substituiertem Heteroarylthioalkyl, gegebenenfalls substituiertem Arylsulfonyl, gegebenenfalls substituiertem Heteroarylsulfonyl, gegebenenfalls substituiertem Aralkylsulfonyl und gegebenenfalls substituiertem Heteroarylalkylsulfonyl, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  7. Verbindung nach einem der Ansprüche 1 bis 5, wobei der nicht interferierende Substituent an dem von RC und RD gebildete Ring ausgewählt ist aus Wasserstoff, Halogen, Alkyl, Aralkyl, Cycloalkyl, gegebenenfalls substituiertem Aryl, Alkoxy, Alkoxyalkyl, gegebenenfalls substituiertem Amino, Hydroxyalkyl, Alkenyl, Alkoxycarbonylalkyl, Heteroarylalkyl oder Hydroxy; und der nicht interferierende Substituent an RB ausgewählt ist aus Halogen, Alkyl, Aralkyl, Cycloalkyl, gegebenenfalls substituiertem Aryl, Alkoxy, Alkoxyalkyl, gegebenenfalls substituiertem Amino, Hydroxyalkyl, Alkenyl, Alkoxycarbonylalkyl, Heteroarylakyl oder Hydroxy, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  8. Verbindung nach einem der Ansprüche 1 bis 7, wobei Z1 eine Bindung oder Alkylen ist, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  9. Verbindung nach einem der Ansprüche 1 bis 8, wobei Z3 eine Bindung oder Alkylen ist, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  10. Verbindung nach einem der Ansprüche 1 bis 9, wobei Z1, Z2 und Z3 nicht gleichzeitig Bindungen sind, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  11. Verbindung nach einem der Ansprüche 1 bis 10, wobei R1 gegebenenfalls substituiertes Cycloalkyl, gegebenenfalls substituiertes Aryl oder gegebenenfalls substituiertes Heteroaryl ist, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  12. Verbindung nach Anspruch 11, wobei R1 gegebenenfalls substituiertes Cycloalkyl ausgewählt aus C3- bis C6-Cycloalkyl, gegebenenfalls substituiertes Aryl ausgewählt aus Phenyl oder Naphthyl, oder gegebenenfalls substituiertes Heteroaryl ausgewählt aus monocyclischem aromatischen heterocyclischem Rest oder kondensiertem aromatischen heterocyclischem Rest ist, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  13. Verbindung nach Anspruch 12, wobei gegebenenfalls substituiertes Heteroaryl ein monocyclischer aromatischer heterocyclischer Rest ist.
  14. Verbindung nach einem der Ansprüche 11 bis 13, wobei der Substituent von gegebenenfalls substituiertem Cycloalkyl, gegebenenfalls substituiertem Aryl und gegebenenfalls substituiertem Heteroaryl ausgewählt ist aus Alkyl, Haloalkyl, Halogen oder Alkoxy, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  15. Verbindung nach einem der Ansprüche 1 bis 14, wobei der Ring C Imidazol-2-yl, Imidazol-4-yl, Pyrazol-3-yl, Triazol-3-yl, Tetrazol-5-yl, Oxazol-2-yl, Oxazol-4-yl, Isoxaxol-3-yl, Thiazol-2-yl, Thiazol-4-yl, 1,3,4-Thiadiazol-2-yl, 1,2,4-Thiadiazol-5-yl, 1,2,4-Thiadiazol-3-yl, 1,3,4-Oxadiazol-2-yl, 1,2,4-Oxadiazol-5-yl, 1,2,4-Oxadiazol-3-yl, Isothiazol-3-yl, Pyridin-2-yl, Pyridazin-3-yl, Pyradin-2-yl, Pyrimidin-2-yl, Pyrimidin-4-yl oder Furazan-3-yl ist, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  16. Verbindung nach Anspruch 15, wobei der Ring C Pyridin-2-yl, Pyrimidin-2-yl, 1,3,4-Oxadiazol-2-yl, 1,2,4-Triazol-3-yl, oder Imidazol-2-yl ist, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  17. Verbindung der Formel (I):
    Figure DE000015187654T1_0006
    wobei RC und RD zusammen genommen mit den angrenzenden Kohlenstoffatomen einen 5- bis 6-gliedrigen Heterocylus bilden, der (ein) Atom(e) N und/oder O enthalten kann und mit einem Benzolring kondensiert sein kann; Y Hydroxy, Mercapto oder Amino ist; Z O, S oder NH ist; RA ein durch die Formel
    Figure DE000015187654T1_0007
    dargestellter Rest ist, wobei der Ring C ein aromatischer Heterocyclus ist, der N enthält, wobei mindestens ein Atom, angrenzend an das Atom an der Bindestelle, ein nicht substituiertes N-Atom ist; die gestrichelte Linie die Anwesenheit oder Abwesenheit einer Bindung darstellt, oder ein durch die Formel
    Figure DE000015187654T1_0008
    dargestellter Rest ist, wobei X O, S oder NH ist; RB Alkyl, Alkoxy, Hydroxy, gegebenenfalls substituiertes Amino, gegebenenfalls substituiertes Aryl, gegebenenfalls substituiertes Heteroaryl, gegebenenfalls substituiertes Cycloalkyl, gegebenenfalls substituiertes Cycloalkenyl oder gegebenenfalls substituierter Heterocyclus ist; mindestens eines von dem von RC und RD gebildeten Ring, Ring C und RB mit einem Rest der Formel -Z1-Z2-Z3-R1 substituiert ist, wobei Z1 und Z3 jeweils unabhängig eine Bindung, gegebenenfalls substituiertes Alkylen oder gegebenenfalls substituiertes Alkenylen sind; Z2 eine Bindung, gegebenenfalls substituiertes Alkylen, gegebenenfalls substituiertes Alkenylen, -CH(OH)-, -S-, -SO-, -SO2-, -SO2N(R2)-, -N(R2)SO2-, -O-, -N(R2)-, -N(R2)CO-, -CON(R2)-, -C(=O)-O-, -O-C(=O) oder -CO- ist; R2 Wasserstoff, gegebenenfalls substituiertes Alkyl, gegebenenfalls substituiertes Alkenyl, gegebenenfalls substituiertes Aryl oder gegebenenfalls substituiertes Heteroaryl ist; R1 gegebenenfalls substituiertes Aryl, gegebenenfalls substituiertes Heteroaryl, gegebenenfalls substituiertes Cycloalkyl, gegebenenfalls substituiertes Cycloalkenyl oder gegebenenfalls substituierter Heterocyclus ist; und der von RC und RD gebildete Ring, der Ring C oder RB gegebenenfalls mit 1 bis 3 Substituenten substituiert ist ausgewählt aus Wasserstoff, Alkyl, Aralkyl, Cycloalkyl, gegebenenfalls substituiertem Aryl, Alkoxy, Alkoxyalkyl, gegebenenfalls substituiertem Amino, Hydroxyalkyl, Alkenyl, Alkoxycarbonylalkyl, Heteroarylalkyl und Hydroxy, an einer Position, an der sich die obige Formel -Z1-Z2-Z3-R1 nicht befindet (wobei Z1, Z2, Z3 und R1 wie vorstehend definiert sind), oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  18. Verbindung nach Anspruch 17, wobei der von RC und RD gebildete Ring ein 5-oder 6-gliedriger Heterocylcus ist, der ein O- und/oder N-Atom enthalten kann und mit einem Benzolring kondensiert sein kann; Y Hydroxy ist; Z O ist; X O ist; der von RC und RD gebildete Ring gegebenenfalls mit 1 bis 3 Substituenten substituiert ist ausgewählt aus Wasserstoff, Alkyl, Aralkyl, Cycloalkyl, gegebenenfalls substituiertem Aryl, Alkoxy, Alkoxyalkyl, gegebenenfalls substituiertem Amino, Hydroxyalkyl, Alkenyl, Alkoxycaronylalkyl und Heteroarylalkyl, und der Ring C und RB gegebenenfalls mit 1 bis 3 Substituenten substituiert ist ausgewählt aus Alkyl, Amino, Halogen und Hydroxy, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  19. Verbindung nach Anspruch 17 oder 18, wobei mindestens eines von der von RC und RD gebildete Ring, der Ring C und RB mit einem Rest der Formel -Z1-Z2-Z3-R1 substituiert ist, wobei Z1 eine Bindung oder Alkylen ist; Z2 Alkylen oder -O- ist; Z3 eine Bindung oder Alkylen ist; R1 gegebenenfalls substituiertes Aryl oder gegebenenfalls substituiertes Heteroaryl ist, oder ein pharmazeutisch verträgliches Salz oder Solvat davon.
  20. Verbindung nach Anspruch 1 bis 19 oder ein pharmazeutisch verträgliches Salz oder Solvat davon zur Verwendung als HIV-Integrase-Inhibitor.
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