ZA200400525B - Isoxazolopyridinones and use thereof in the treatment of parkinson's disease. - Google Patents
Isoxazolopyridinones and use thereof in the treatment of parkinson's disease. Download PDFInfo
- Publication number
- ZA200400525B ZA200400525B ZA200400525A ZA200400525A ZA200400525B ZA 200400525 B ZA200400525 B ZA 200400525B ZA 200400525 A ZA200400525 A ZA 200400525A ZA 200400525 A ZA200400525 A ZA 200400525A ZA 200400525 B ZA200400525 B ZA 200400525B
- Authority
- ZA
- South Africa
- Prior art keywords
- compound
- phenyl
- hydroxy
- methyl
- free base
- Prior art date
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- 208000018737 Parkinson disease Diseases 0.000 title claims description 13
- WJLKGZPFGUBCPD-UHFFFAOYSA-N 1h-[1,2]oxazolo[4,3-b]pyridin-3-one Chemical class C1=CN=C2C(=O)ONC2=C1 WJLKGZPFGUBCPD-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 75
- 150000003839 salts Chemical group 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 17
- 239000012458 free base Substances 0.000 claims description 16
- -1 benzo[1 ,2,5]oxadiazol-5-yl Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- KPXIVOYDTAKEBC-UHFFFAOYSA-N 6-[4-[(dimethylamino)methyl]phenyl]-3-phenyl-5H-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=CC(CN(C)C)=CC=C1C(NC1=O)=CC2=C1C(C=1C=CC=CC=1)=NO2 KPXIVOYDTAKEBC-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229940088679 drug related substance Drugs 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- YCAACZFPADQMAR-UHFFFAOYSA-N 6-[4-(2-methoxyethoxymethyl)phenyl]-5-methyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=CC(COCCOC)=CC=C1C(N(C1=O)C)=CC2=C1C(C=1C=CC=CC=1)=NO2 YCAACZFPADQMAR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 9
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 238000001819 mass spectrum Methods 0.000 description 39
- 239000007787 solid Substances 0.000 description 34
- 239000000243 solution Substances 0.000 description 26
- 239000003795 chemical substances by application Substances 0.000 description 19
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 101150026563 NR4A2 gene Proteins 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
- 150000002825 nitriles Chemical class 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- DCKOQOHEZADEJX-UHFFFAOYSA-N n,5-dimethyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CNC(=O)C1=C(C)ON=C1C1=CC=CC=C1 DCKOQOHEZADEJX-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- LWRSYTXEQUUTKW-UHFFFAOYSA-N 2,4-dimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1 LWRSYTXEQUUTKW-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
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- 108700008625 Reporter Genes Proteins 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 229960003638 dopamine Drugs 0.000 description 4
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- 210000001259 mesencephalon Anatomy 0.000 description 4
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- CABBIZSFTLIHJT-UHFFFAOYSA-N 5-methyl-3,6-diphenyl-[1,2]oxazolo[4,3-c]pyridin-4-one Chemical compound C=12C(=O)N(C)C(C=3C=CC=CC=3)=CC2=NOC=1C1=CC=CC=C1 CABBIZSFTLIHJT-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
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- PPUUWHCQKUSMQV-UHFFFAOYSA-N 6-[4-(2-hydroxyethoxymethyl)phenyl]-5-methyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C=3C=CC(COCCO)=CC=3)=CC=2ON=C1C1=CC=CC=C1 PPUUWHCQKUSMQV-UHFFFAOYSA-N 0.000 description 2
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- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- FEIOASZZURHTHB-UHFFFAOYSA-N Methyl-p-formylbenzoate Natural products COC(=O)C1=CC=C(C=O)C=C1 FEIOASZZURHTHB-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
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- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 2
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- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
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- DQNUZURLZCIRLZ-UHFFFAOYSA-N n,3-dimethyl-5-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC1=NOC(C=2C=CC=CC=2)=C1C(=O)NC DQNUZURLZCIRLZ-UHFFFAOYSA-N 0.000 description 2
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- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
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- GJNGXPDXRVXSEH-UHFFFAOYSA-N 4-chlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1 GJNGXPDXRVXSEH-UHFFFAOYSA-N 0.000 description 1
- VCZNNAKNUVJVGX-UHFFFAOYSA-N 4-methylbenzonitrile Chemical compound CC1=CC=C(C#N)C=C1 VCZNNAKNUVJVGX-UHFFFAOYSA-N 0.000 description 1
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- BTYZVJMWTDCGTR-UHFFFAOYSA-N 5,6-dimethyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C)=CC=2ON=C1C1=CC=CC=C1 BTYZVJMWTDCGTR-UHFFFAOYSA-N 0.000 description 1
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- PENHKTNQUJMHIR-UHFFFAOYSA-N 5-methyl-3-phenyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=CC=C1 PENHKTNQUJMHIR-UHFFFAOYSA-N 0.000 description 1
- QKGMJCLWMCCRRB-UHFFFAOYSA-N 5-methyl-3-phenyl-6-[4-(phenylmethoxymethyl)phenyl]-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C=3C=CC(COCC=4C=CC=CC=4)=CC=3)=CC=2ON=C1C1=CC=CC=C1 QKGMJCLWMCCRRB-UHFFFAOYSA-N 0.000 description 1
- IBQKWQHKJWZQRA-UHFFFAOYSA-N 5-methyl-3-phenyl-6-[4-(pyrrol-1-ylmethyl)phenyl]-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C=3C=CC(CN4C=CC=C4)=CC=3)=CC=2ON=C1C1=CC=CC=C1 IBQKWQHKJWZQRA-UHFFFAOYSA-N 0.000 description 1
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- QIPODYCQCKHDDA-UHFFFAOYSA-N 6-[4-[(dimethylamino)methyl]phenyl]-3-phenyl-5H-[1,2]oxazolo[4,3-c]pyridin-4-one Chemical compound C1=CC(CN(C)C)=CC=C1C1=CC2=NOC(C=3C=CC=CC=3)=C2C(=O)N1 QIPODYCQCKHDDA-UHFFFAOYSA-N 0.000 description 1
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- FMSSTTMLKQLLII-UHFFFAOYSA-N 6-cyclohexyl-5-methyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C3CCCCC3)=CC=2ON=C1C1=CC=CC=C1 FMSSTTMLKQLLII-UHFFFAOYSA-N 0.000 description 1
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- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 238000011795 OF1 mouse Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- YSXKPIUOCJLQIE-UHFFFAOYSA-N biperiden Chemical compound C1C(C=C2)CC2C1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 YSXKPIUOCJLQIE-UHFFFAOYSA-N 0.000 description 1
- 229960003003 biperiden Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
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- 230000018109 developmental process Effects 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
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- 210000004002 dopaminergic cell Anatomy 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 description 1
- 229960003337 entacapone Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
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- 239000003112 inhibitor Substances 0.000 description 1
- 150000002545 isoxazoles Chemical class 0.000 description 1
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- 239000003446 ligand Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- JTUQHTUQSMTHHC-UHFFFAOYSA-N methyl 4-(5-methyl-4-oxo-3-phenyl-[1,2]oxazolo[4,3-c]pyridin-6-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC2=NOC(C=3C=CC=CC=3)=C2C(=O)N1C JTUQHTUQSMTHHC-UHFFFAOYSA-N 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 description 1
- 230000009427 motor defect Effects 0.000 description 1
- HCUIEGLRDNPODU-UHFFFAOYSA-N n-cyclopropyl-5-methyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C(=O)NC1CC1 HCUIEGLRDNPODU-UHFFFAOYSA-N 0.000 description 1
- WUZODTCWKPXULS-UHFFFAOYSA-N n-ethyl-5-methyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CCNC(=O)C1=C(C)ON=C1C1=CC=CC=C1 WUZODTCWKPXULS-UHFFFAOYSA-N 0.000 description 1
- MFDUBANTKQQBFU-UHFFFAOYSA-N n-methoxy-4-(2-methoxyethoxymethyl)-n-methylbenzamide Chemical compound COCCOCC1=CC=C(C(=O)N(C)OC)C=C1 MFDUBANTKQQBFU-UHFFFAOYSA-N 0.000 description 1
- NCCHARWOCKOHIH-UHFFFAOYSA-N n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1 NCCHARWOCKOHIH-UHFFFAOYSA-N 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- 102000006255 nuclear receptors Human genes 0.000 description 1
- 108091008686 nuclear receptors type II Proteins 0.000 description 1
- 102000027507 nuclear receptors type II Human genes 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- QVYRGXJJSLMXQH-UHFFFAOYSA-N orphenadrine Chemical compound C=1C=CC=C(C)C=1C(OCCN(C)C)C1=CC=CC=C1 QVYRGXJJSLMXQH-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960003089 pramipexole Drugs 0.000 description 1
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 229960003946 selegiline Drugs 0.000 description 1
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229960004603 tolcapone Drugs 0.000 description 1
- MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
Classifications
-
- 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
- A61K31/435—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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0119911.6A GB0119911D0 (en) | 2001-08-15 | 2001-08-15 | Organic Compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200400525B true ZA200400525B (en) | 2005-04-01 |
Family
ID=9920454
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200400525A ZA200400525B (en) | 2001-08-15 | 2004-01-23 | Isoxazolopyridinones and use thereof in the treatment of parkinson's disease. |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US7087756B2 (enExample) |
| EP (1) | EP1418912B1 (enExample) |
| JP (1) | JP2005501847A (enExample) |
| KR (1) | KR20040029429A (enExample) |
| CN (1) | CN100384418C (enExample) |
| AR (1) | AR036351A1 (enExample) |
| AT (1) | ATE355059T1 (enExample) |
| BR (1) | BR0211903A (enExample) |
| CA (1) | CA2454762A1 (enExample) |
| CO (1) | CO5560566A2 (enExample) |
| DE (1) | DE60218484T2 (enExample) |
| EC (1) | ECSP044971A (enExample) |
| ES (1) | ES2282467T3 (enExample) |
| GB (1) | GB0119911D0 (enExample) |
| HU (1) | HUP0401325A3 (enExample) |
| IL (1) | IL160018A0 (enExample) |
| MX (1) | MXPA04001419A (enExample) |
| NO (1) | NO20040659L (enExample) |
| PE (1) | PE20030356A1 (enExample) |
| PL (1) | PL366848A1 (enExample) |
| PT (1) | PT1418912E (enExample) |
| RU (1) | RU2004107847A (enExample) |
| WO (1) | WO2003015780A2 (enExample) |
| ZA (1) | ZA200400525B (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1408042A4 (en) * | 2001-06-14 | 2005-02-02 | Banyu Pharma Co Ltd | NEW ISOXAZOLOPYRIDONE DERIVATIVES AND THEIR USE |
| US7820705B2 (en) * | 2004-05-14 | 2010-10-26 | Irm Llc | Compounds and compositions as PPAR modulators |
| AU2007217892A1 (en) * | 2006-02-16 | 2007-08-30 | The Mclean Hospital Corporation | Methods and compositions for the treatment of Parkinson's Disease |
| EP2051977A2 (en) | 2006-07-20 | 2009-04-29 | Amgen Inc. | SUBSTITUTED AZOLE AROMATIC HETEROCYCLES AS INHIBITORS OF LLbeta-HSD-1 |
| FR2906250B1 (fr) * | 2006-09-22 | 2008-10-31 | Sanofi Aventis Sa | Derives de 2-aryl-6phenyl-imidazo(1,2-a) pyridines, leur preparation et leur application en therapeutique |
| FR2933609B1 (fr) * | 2008-07-10 | 2010-08-27 | Fournier Lab Sa | Utilisation de derives d'indole comme activateurs de nurr-1, pour le traitement de la maladie de parkinson. |
| US8173670B2 (en) * | 2009-01-13 | 2012-05-08 | Van Andel Research Institute | Methods of using substituted isoxazolo pyridinones as dissociated glucocorticoids |
| FR2950053B1 (fr) | 2009-09-11 | 2014-08-01 | Fournier Lab Sa | Utilisation de derives d'indole benzoique comme activateurs de nurr-1, pour le traitement de la maladie de parkinson |
| FR2955110A1 (fr) | 2010-01-08 | 2011-07-15 | Fournier Lab Sa | Nouveaux derives de type pyrrolopyridine benzoique |
| DE102011085038A1 (de) | 2011-10-21 | 2013-04-25 | Tesa Se | Verfahren zur Kapselung einer elektronischen Anordnung |
| EP3049089B1 (en) | 2013-09-25 | 2019-08-21 | Van Andel Research Institute | Highly potent glucocorticoids |
| KR20170033630A (ko) | 2015-09-17 | 2017-03-27 | (주)다올 | 도로용 경계블럭 |
| EP3525870B1 (en) | 2016-10-14 | 2023-05-10 | Van Andel Research Institute | Highly potent glucocorticoids |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE7602542L (sv) | 1975-03-14 | 1976-09-15 | Sandoz Ag | 3-(alfa-iminobensyl)-4-hydroxi-2(lh)-pyridoner |
| US4064251A (en) * | 1976-06-25 | 1977-12-20 | Sandoz, Inc. | Substituted hydroxy pyridones |
| US4049813A (en) * | 1976-07-15 | 1977-09-20 | Sandoz, Inc. | Substituted isoxazolo pyridinones |
| DE2801190A1 (de) * | 1977-01-19 | 1978-07-20 | Sandoz Ag | 3-(alpha-iminobenzyl)-4-hydroxy-2(1h)- pyridon-derivat |
| US4238616A (en) * | 1977-01-19 | 1980-12-09 | Sandoz, Inc. | 3-(Substituted)phenyl-5-(β-hydroxyphenethyl)-N-(alkyl)-isoxazole-4-carboxamides |
| US4113727A (en) * | 1977-04-26 | 1978-09-12 | Sandoz, Inc. | Process for the preparation of substituted isoxazolo[4,5-c]pyridin-4-(5H)-ones |
| EP1408042A4 (en) * | 2001-06-14 | 2005-02-02 | Banyu Pharma Co Ltd | NEW ISOXAZOLOPYRIDONE DERIVATIVES AND THEIR USE |
-
2001
- 2001-08-15 GB GBGB0119911.6A patent/GB0119911D0/en not_active Ceased
-
2002
- 2002-08-13 AR ARP020103046A patent/AR036351A1/es unknown
- 2002-08-14 CN CNB028159268A patent/CN100384418C/zh not_active Expired - Fee Related
- 2002-08-14 EP EP02772157A patent/EP1418912B1/en not_active Expired - Lifetime
- 2002-08-14 PL PL02366848A patent/PL366848A1/xx not_active Application Discontinuation
- 2002-08-14 PT PT02772157T patent/PT1418912E/pt unknown
- 2002-08-14 DE DE60218484T patent/DE60218484T2/de not_active Expired - Lifetime
- 2002-08-14 IL IL16001802A patent/IL160018A0/xx unknown
- 2002-08-14 RU RU2004107847/15A patent/RU2004107847A/ru not_active Application Discontinuation
- 2002-08-14 BR BR0211903-0A patent/BR0211903A/pt not_active IP Right Cessation
- 2002-08-14 JP JP2003520739A patent/JP2005501847A/ja not_active Withdrawn
- 2002-08-14 WO PCT/EP2002/009134 patent/WO2003015780A2/en not_active Ceased
- 2002-08-14 ES ES02772157T patent/ES2282467T3/es not_active Expired - Lifetime
- 2002-08-14 HU HU0401325A patent/HUP0401325A3/hu unknown
- 2002-08-14 AT AT02772157T patent/ATE355059T1/de not_active IP Right Cessation
- 2002-08-14 KR KR10-2004-7002124A patent/KR20040029429A/ko not_active Ceased
- 2002-08-14 MX MXPA04001419A patent/MXPA04001419A/es unknown
- 2002-08-14 PE PE2002000734A patent/PE20030356A1/es not_active Application Discontinuation
- 2002-08-14 US US10/486,569 patent/US7087756B2/en not_active Expired - Fee Related
- 2002-08-14 CA CA002454762A patent/CA2454762A1/en not_active Abandoned
-
2004
- 2004-01-23 ZA ZA200400525A patent/ZA200400525B/en unknown
- 2004-02-03 EC EC2004004971A patent/ECSP044971A/es unknown
- 2004-02-13 NO NO20040659A patent/NO20040659L/no not_active Application Discontinuation
- 2004-03-12 CO CO04023011A patent/CO5560566A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| RU2004107847A (ru) | 2005-05-10 |
| ECSP044971A (es) | 2004-03-23 |
| PE20030356A1 (es) | 2003-05-14 |
| CN100384418C (zh) | 2008-04-30 |
| EP1418912A2 (en) | 2004-05-19 |
| ES2282467T3 (es) | 2007-10-16 |
| BR0211903A (pt) | 2004-09-21 |
| WO2003015780A8 (en) | 2004-05-21 |
| ATE355059T1 (de) | 2006-03-15 |
| CN1635889A (zh) | 2005-07-06 |
| NO20040659D0 (no) | 2004-02-13 |
| EP1418912B1 (en) | 2007-02-28 |
| CA2454762A1 (en) | 2003-02-27 |
| GB0119911D0 (en) | 2001-10-10 |
| PT1418912E (pt) | 2007-05-31 |
| MXPA04001419A (es) | 2004-05-27 |
| HUP0401325A3 (en) | 2005-09-28 |
| WO2003015780A3 (en) | 2003-11-13 |
| US7087756B2 (en) | 2006-08-08 |
| JP2005501847A (ja) | 2005-01-20 |
| KR20040029429A (ko) | 2004-04-06 |
| AR036351A1 (es) | 2004-09-01 |
| NO20040659L (no) | 2004-02-13 |
| HUP0401325A2 (hu) | 2004-10-28 |
| PL366848A1 (en) | 2005-02-07 |
| WO2003015780A2 (en) | 2003-02-27 |
| DE60218484T2 (de) | 2007-11-15 |
| IL160018A0 (en) | 2004-06-20 |
| DE60218484D1 (de) | 2007-04-12 |
| US20040248893A1 (en) | 2004-12-09 |
| CO5560566A2 (es) | 2005-09-30 |
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