ES2284964T3 - Nuevos derivados de indol-2-ona. - Google Patents
Nuevos derivados de indol-2-ona. Download PDFInfo
- Publication number
- ES2284964T3 ES2284964T3 ES02793678T ES02793678T ES2284964T3 ES 2284964 T3 ES2284964 T3 ES 2284964T3 ES 02793678 T ES02793678 T ES 02793678T ES 02793678 T ES02793678 T ES 02793678T ES 2284964 T3 ES2284964 T3 ES 2284964T3
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- Prior art keywords
- alkyl
- alkoxy
- hydrogen
- independently
- rent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 206010012289 Dementia Diseases 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 201000010099 disease Diseases 0.000 claims abstract description 18
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 17
- 230000002265 prevention Effects 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 5
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 96
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 239000001257 hydrogen Substances 0.000 claims description 56
- 229910052760 oxygen Inorganic materials 0.000 claims description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
- 229910052717 sulfur Inorganic materials 0.000 claims description 47
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 150000002431 hydrogen Chemical class 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 27
- -1 trifluoromethoxy, cyano, amino Chemical group 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
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- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 9
- 125000001589 carboacyl group Chemical group 0.000 claims description 9
- 239000012458 free base Substances 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 230000007170 pathology Effects 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 201000004384 Alopecia Diseases 0.000 claims description 6
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 6
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
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- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 5
- 230000004770 neurodegeneration Effects 0.000 claims description 5
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
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- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 230000006999 cognitive decline Effects 0.000 claims description 4
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims description 4
- 230000003676 hair loss Effects 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- WLLRPFPHVRJYBG-UHFFFAOYSA-N 3-[6-(2-methoxyethoxy)isoquinolin-1-yl]-2-oxo-1,3-dihydroindole-5-carbonitrile Chemical group O=C1NC2=CC=C(C#N)C=C2C1C1=NC=CC2=CC(OCCOC)=CC=C21 WLLRPFPHVRJYBG-UHFFFAOYSA-N 0.000 claims description 3
- JXIMQRCXMARPHT-UHFFFAOYSA-N 3-[6-[2-(2-methoxyethoxy)ethoxy]isoquinolin-1-yl]-2-oxo-1,3-dihydroindole-5-carbonitrile;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1NC2=CC=C(C#N)C=C2C1C1=NC=CC2=CC(OCCOCCOC)=CC=C21 JXIMQRCXMARPHT-UHFFFAOYSA-N 0.000 claims description 3
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- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 230000007423 decrease Effects 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 208000024963 hair loss Diseases 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 3
- NZZCNZYQMWLVCQ-UHFFFAOYSA-N methyl 2-hydroxy-3-(5,6,7,8-tetrahydroquinazolin-4-yl)-1H-indole-5-carboxylate Chemical compound C1CCCC2=C1N=CN=C2C1=C(O)NC2=CC=C(C(=O)OC)C=C21 NZZCNZYQMWLVCQ-UHFFFAOYSA-N 0.000 claims description 3
- PAGNCSCNSYJTIB-UHFFFAOYSA-N methyl 2-hydroxy-3-thieno[2,3-d]pyrimidin-4-yl-1H-indole-5-carboxylate Chemical compound C12=CC(C(=O)OC)=CC=C2NC(O)=C1C1=NC=NC2=C1C=CS2 PAGNCSCNSYJTIB-UHFFFAOYSA-N 0.000 claims description 3
- 230000000750 progressive effect Effects 0.000 claims description 3
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 3
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 2
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 2
- ULSGICPPPXWHNK-UHFFFAOYSA-N 3-[6-[2-(2-methoxyethoxy)ethoxy]isoquinolin-1-yl]-2-oxo-1,3-dihydroindole-5-carbonitrile Chemical compound O=C1NC2=CC=C(C#N)C=C2C1C1=NC=CC2=CC(OCCOCCOC)=CC=C21 ULSGICPPPXWHNK-UHFFFAOYSA-N 0.000 claims description 2
- 208000000044 Amnesia Diseases 0.000 claims description 2
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 201000002832 Lewy body dementia Diseases 0.000 claims description 2
- 208000026139 Memory disease Diseases 0.000 claims description 2
- 201000004810 Vascular dementia Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 239000003433 contraceptive agent Substances 0.000 claims description 2
- 230000002254 contraceptive effect Effects 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 230000006984 memory degeneration Effects 0.000 claims description 2
- 206010027175 memory impairment Diseases 0.000 claims description 2
- 208000023060 memory loss Diseases 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 230000001149 cognitive effect Effects 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims 1
- 231100000360 alopecia Toxicity 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000010901 lateral sclerosis Diseases 0.000 claims 1
- 208000005264 motor neuron disease Diseases 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 abstract description 40
- 239000000543 intermediate Substances 0.000 abstract description 9
- 230000008569 process Effects 0.000 abstract description 5
- 102000001267 GSK3 Human genes 0.000 abstract 1
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 39
- 239000000243 solution Substances 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 29
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 14
- 239000003921 oil Substances 0.000 description 13
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000012267 brine Substances 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 description 7
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- 102000015735 Beta-catenin Human genes 0.000 description 6
- 108060000903 Beta-catenin Proteins 0.000 description 6
- 208000020925 Bipolar disease Diseases 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 125000001544 thienyl group Chemical group 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 125000002541 furyl group Chemical group 0.000 description 5
- 125000002883 imidazolyl group Chemical group 0.000 description 5
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- 125000000842 isoxazolyl group Chemical group 0.000 description 5
- 229910052744 lithium Inorganic materials 0.000 description 5
- 125000002971 oxazolyl group Chemical group 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 125000000168 pyrrolyl group Chemical group 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 125000000335 thiazolyl group Chemical group 0.000 description 5
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 108010001483 Glycogen Synthase Proteins 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
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- 125000002632 imidazolidinyl group Chemical group 0.000 description 4
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
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- 125000002757 morpholinyl group Chemical group 0.000 description 4
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 125000004193 piperazinyl group Chemical group 0.000 description 4
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- 239000011541 reaction mixture Substances 0.000 description 4
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- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
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- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 4
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- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
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- 241000124008 Mammalia Species 0.000 description 3
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- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 208000014060 Niemann-Pick disease Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 3
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
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- 238000011161 development Methods 0.000 description 3
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- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Psychology (AREA)
- Reproductive Health (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Gynecology & Obstetrics (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0104340A SE0104340D0 (sv) | 2001-12-20 | 2001-12-20 | New compounds |
| SE0104340 | 2001-12-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2284964T3 true ES2284964T3 (es) | 2007-11-16 |
Family
ID=20286439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02793678T Expired - Lifetime ES2284964T3 (es) | 2001-12-20 | 2002-12-18 | Nuevos derivados de indol-2-ona. |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7205314B2 (enExample) |
| EP (1) | EP1458707B1 (enExample) |
| JP (2) | JP4465188B2 (enExample) |
| AT (1) | ATE361287T1 (enExample) |
| AU (1) | AU2002359164A1 (enExample) |
| DE (1) | DE60219954T2 (enExample) |
| ES (1) | ES2284964T3 (enExample) |
| SE (1) | SE0104340D0 (enExample) |
| WO (1) | WO2003053330A2 (enExample) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002359162A1 (en) | 2001-12-21 | 2003-07-15 | Astrazeneca Ab | Use of oxindole derivatives in the treatment of dementia related diseases, alzheimer's disease and conditions associated with glycogen synthase kinase-3 |
| SE0200979D0 (sv) * | 2002-03-28 | 2002-03-28 | Astrazeneca Ab | New compounds |
| SE0302546D0 (sv) * | 2003-09-24 | 2003-09-24 | Astrazeneca Ab | New compounds |
| US20040242568A1 (en) | 2003-03-25 | 2004-12-02 | Syrrx, Inc. | Dipeptidyl peptidase inhibitors |
| JP2007511467A (ja) | 2003-05-14 | 2007-05-10 | タケダ サン ディエゴ インコーポレイテッド | ジペプチジルペプチダーゼインヒビター |
| MXPA06001601A (es) | 2003-08-13 | 2006-08-25 | Takeda Pharmaceutical | Derivados de 4-pirimidona y su uso como inhibidores de dipeptidilpeptidasa. |
| SG146683A1 (en) | 2003-09-17 | 2008-10-30 | Janssen Pharmaceutica Nv | Fused heterocyclic compounds as serotonin receptor modulators |
| WO2006023931A2 (en) | 2004-08-18 | 2006-03-02 | Takeda San Diego, Inc. | Kinase inhibitors |
| EP1812439B2 (en) | 2004-10-15 | 2017-12-06 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| EP1899322B1 (en) | 2005-06-28 | 2009-09-02 | Sanofi-Aventis | Isoquinoline derivatives as inhibitors of rho-kinase |
| HRP20110839T1 (hr) | 2005-07-26 | 2011-12-31 | Sanofi | Derivati cikloheksaminizokinolona kao inhibitori rho-kinaze |
| PT1910333E (pt) | 2005-07-26 | 2013-08-01 | Sanofi Sa | Derivados de isoquinolona substituída com piperidinilo como inibidores da rho-cinase |
| US7598255B2 (en) | 2005-08-04 | 2009-10-06 | Janssen Pharmaceutica Nv | Pyrimidine compounds as serotonin receptor modulators |
| EP2275096A3 (en) | 2005-08-26 | 2011-07-13 | Braincells, Inc. | Neurogenesis via modulation of the muscarinic receptors |
| EP2258357A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| NZ566799A (en) | 2005-09-14 | 2011-04-29 | Takeda Pharmaceutical | Dipeptidyl peptidase inhibitors for treating diabetes |
| WO2007035629A2 (en) | 2005-09-16 | 2007-03-29 | Takeda Pharmaceutical Company Limited | Process for the preparation of pyrimidinedione derivatives |
| US8119655B2 (en) | 2005-10-07 | 2012-02-21 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| WO2007047978A2 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| EP2314289A1 (en) | 2005-10-31 | 2011-04-27 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| WO2007100880A1 (en) * | 2006-02-28 | 2007-09-07 | Amgen Inc. | Cinnoline and quinazoline derivates as phosphodiesterase 10 inhibitors |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| WO2007112347A1 (en) | 2006-03-28 | 2007-10-04 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| EP2021000A2 (en) | 2006-05-09 | 2009-02-11 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| US7851468B2 (en) * | 2006-05-15 | 2010-12-14 | Cephalon, Inc. | Substituted pyrazolo[3,4-d]pyrimidines |
| US8324383B2 (en) | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| JP2010505962A (ja) | 2006-10-09 | 2010-02-25 | 武田薬品工業株式会社 | キナーゼ阻害剤 |
| WO2008046919A2 (en) | 2006-10-21 | 2008-04-24 | Abbott Gmbh & Co. Kg | Heterocyclic compounds and their use as glycogen synthase kinase 3 inhibitors |
| TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| ATE502027T1 (de) | 2006-12-27 | 2011-04-15 | Sanofi Aventis | Substituierte isochinoline und ihre verwendung als rho-kinase-inhibitoren |
| AU2007338410B2 (en) | 2006-12-27 | 2012-08-16 | Sanofi-Aventis | Cycloalkylamine substituted isoquinoline derivatives |
| KR20090094338A (ko) | 2006-12-27 | 2009-09-04 | 사노피-아벤티스 | 치환된 이소퀴놀린 및 이소퀴놀리논 유도체 |
| EP2102164B1 (en) | 2006-12-27 | 2010-12-01 | Sanofi-Aventis | Cycloalkylamine substituted isoquinoline and isoquinolinone derivatives |
| CN101595094B (zh) | 2006-12-27 | 2013-02-20 | 塞诺菲-安万特股份有限公司 | 环烷基胺取代的异喹诺酮衍生物 |
| BRPI0720710A2 (pt) | 2006-12-27 | 2014-12-23 | Sanofi Aventis | Derivados de isoquinolona e isoquinolinona substituídos com cicloalquilamina |
| JP5421783B2 (ja) | 2006-12-27 | 2014-02-19 | サノフイ | Ｒｈｏキナーゼ阻害剤としての置換イソキノロン及びイソキノリノン誘導体 |
| US8093236B2 (en) | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
| US20090291982A1 (en) * | 2008-05-22 | 2009-11-26 | Astrazeneca Ab | New Substituted Oxindole Derivative 352 |
| PE20110059A1 (es) | 2008-06-24 | 2011-02-15 | Sanofi Aventis | Isoquinolinas e isoquinolinonas sustituidas en calidad de inhibidores de la rho-quinasa |
| SI2303845T1 (sl) | 2008-06-24 | 2013-12-31 | Sanofi | Bi- in policiklični substituirani izokinolin in izokinolinski derivati kot inhibitorji rho-kinaze |
| PL2313374T3 (pl) | 2008-06-24 | 2014-03-31 | Sanofi Sa | 6-podstawione izochinoliny i izochinolinony |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| TW201040191A (en) | 2009-03-27 | 2010-11-16 | Abbott Gmbh & Co Kg | Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors |
| US9266855B2 (en) | 2010-09-27 | 2016-02-23 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors |
| US9090592B2 (en) | 2010-12-30 | 2015-07-28 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors |
| WO2023097151A1 (en) * | 2021-11-29 | 2023-06-01 | Woolsey Pharmaceuticals, Inc. | Methods of treating agitation and other dementia-associated behavioral symptoms |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW574214B (en) * | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
| GB9707800D0 (en) | 1996-05-06 | 1997-06-04 | Zeneca Ltd | Chemical compounds |
| DE69838172T2 (de) * | 1997-08-22 | 2008-04-10 | Astrazeneca Ab | Oxindolylchinazolinderivate als angiogenesehemmer |
| CN1161333C (zh) | 1998-08-20 | 2004-08-11 | 住友制药株式会社 | 作为生长激素释放剂的2-羟基吲哚衍生物 |
| EP1136493A1 (en) | 2000-03-23 | 2001-09-26 | Sanofi-Synthelabo | 2-(Thienopyridinyl)pyrimidone, 2-(furopyridinyl)pyrimidone 2-(isoquinolinyl)pyrimidone, 2-(pyridoindolyl)pyrimidone and 2-(benzofuropyridinyl)pyrimidone derivatives |
-
2001
- 2001-12-20 SE SE0104340A patent/SE0104340D0/xx unknown
-
2002
- 2002-12-18 AU AU2002359164A patent/AU2002359164A1/en not_active Abandoned
- 2002-12-18 US US10/499,217 patent/US7205314B2/en not_active Expired - Fee Related
- 2002-12-18 WO PCT/SE2002/002373 patent/WO2003053330A2/en not_active Ceased
- 2002-12-18 AT AT02793678T patent/ATE361287T1/de not_active IP Right Cessation
- 2002-12-18 ES ES02793678T patent/ES2284964T3/es not_active Expired - Lifetime
- 2002-12-18 JP JP2003554090A patent/JP4465188B2/ja not_active Expired - Fee Related
- 2002-12-18 EP EP02793678A patent/EP1458707B1/en not_active Expired - Lifetime
- 2002-12-18 DE DE60219954T patent/DE60219954T2/de not_active Expired - Lifetime
-
2009
- 2009-09-01 JP JP2009201189A patent/JP2009280618A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20050065170A1 (en) | 2005-03-24 |
| AU2002359164A1 (en) | 2003-07-09 |
| JP2009280618A (ja) | 2009-12-03 |
| WO2003053330A2 (en) | 2003-07-03 |
| JP4465188B2 (ja) | 2010-05-19 |
| US7205314B2 (en) | 2007-04-17 |
| AU2002359164A8 (en) | 2003-07-09 |
| EP1458707B1 (en) | 2007-05-02 |
| DE60219954D1 (de) | 2007-06-14 |
| SE0104340D0 (sv) | 2001-12-20 |
| EP1458707A2 (en) | 2004-09-22 |
| DE60219954T2 (de) | 2008-01-17 |
| ATE361287T1 (de) | 2007-05-15 |
| WO2003053330A3 (en) | 2003-10-30 |
| JP2005513082A (ja) | 2005-05-12 |
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