ES2320905T3 - Nuevas 5-acilindolinonas con contenido en alquilo, su preparacion y su uso como medicamentos. - Google Patents
Nuevas 5-acilindolinonas con contenido en alquilo, su preparacion y su uso como medicamentos. Download PDFInfo
- Publication number
- ES2320905T3 ES2320905T3 ES05715811T ES05715811T ES2320905T3 ES 2320905 T3 ES2320905 T3 ES 2320905T3 ES 05715811 T ES05715811 T ES 05715811T ES 05715811 T ES05715811 T ES 05715811T ES 2320905 T3 ES2320905 T3 ES 2320905T3
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- Spain
- Prior art keywords
- alkyl
- group
- amino
- carbonyl
- alkoxy
- 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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- 238000002360 preparation method Methods 0.000 title claims description 26
- 239000003814 drug Substances 0.000 title claims description 9
- 229940079593 drug Drugs 0.000 title claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 216
- -1 nitro, cyano, amino Chemical group 0.000 claims abstract description 99
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 85
- 150000001875 compounds Chemical class 0.000 claims abstract description 75
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 45
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 34
- 239000000203 mixture Substances 0.000 claims abstract description 26
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 22
- 239000000460 chlorine Substances 0.000 claims abstract description 20
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 19
- 125000006842 cycloalkyleneimino group Chemical group 0.000 claims abstract description 19
- 125000001424 substituent group Chemical group 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 125000004429 atom Chemical group 0.000 claims abstract description 17
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000011737 fluorine Substances 0.000 claims abstract description 16
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 16
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 16
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 13
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 13
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
- 239000001301 oxygen Substances 0.000 claims abstract description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims abstract description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000003277 amino group Chemical group 0.000 claims abstract description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 8
- 125000005129 aryl carbonyl group Chemical group 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims abstract description 7
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 125000006602 (C1-C3) alkylsulfonylamino group Chemical group 0.000 claims abstract description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims abstract description 6
- 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims abstract description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 5
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 5
- 125000006597 (C1-C3) alkylcarbonylamino group Chemical group 0.000 claims abstract description 4
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 4
- 239000011630 iodine Substances 0.000 claims abstract description 4
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 4
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims abstract description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 3
- 125000001769 aryl amino group Chemical group 0.000 claims abstract description 3
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims abstract description 3
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims abstract description 3
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 3
- 125000005241 heteroarylamino group Chemical group 0.000 claims abstract description 3
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims abstract description 3
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims abstract description 3
- 125000005553 heteroaryloxy group Chemical group 0.000 claims abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- 125000005544 phthalimido group Chemical group 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims description 44
- 239000000126 substance Substances 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 239000011593 sulfur Substances 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 208000012902 Nervous system disease Diseases 0.000 claims description 4
- 208000025966 Neurological disease Diseases 0.000 claims description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 3
- 230000003412 degenerative effect Effects 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 150000003951 lactams Chemical group 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- PRRYKQCBNLEMKK-UHFFFAOYSA-N 5-acetyl-3-[(3,4-difluorophenyl)-(2,2-dimethylhydrazinyl)methylidene]-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C(C)=O)C=C2C1=C(NN(C)C)C1=CC=C(F)C(F)=C1 PRRYKQCBNLEMKK-UHFFFAOYSA-N 0.000 claims description 2
- GEDCCZDGOSWMCN-UHFFFAOYSA-N 5-acetyl-3-[8-(dimethylamino)oct-2-en-4-ylidene]-1h-indol-2-one Chemical compound C1=C(C(C)=O)C=C2C(=C(CCCCN(C)C)C=CC)C(=O)NC2=C1 GEDCCZDGOSWMCN-UHFFFAOYSA-N 0.000 claims description 2
- RRIMEAIVEAJAJM-UHFFFAOYSA-N 5-acetyl-3-[phenyl(propylamino)methylidene]-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C(C)=O)C=C2C1=C(NCCC)C1=CC=CC=C1 RRIMEAIVEAJAJM-UHFFFAOYSA-N 0.000 claims description 2
- HFWLYTNHGAQFOU-UHFFFAOYSA-N 5-acetyl-3-[phenyl-(3-pyridin-3-ylpropylamino)methylidene]-1h-indol-2-one Chemical compound C12=CC(C(=O)C)=CC=C2NC(=O)C1=C(C=1C=CC=CC=1)NCCCC1=CC=CN=C1 HFWLYTNHGAQFOU-UHFFFAOYSA-N 0.000 claims description 2
- OYSQUGVVMMVTHE-UHFFFAOYSA-N 5-acetyl-3-[phenyl-(propan-2-ylamino)methylidene]-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C(C)=O)C=C2C1=C(NC(C)C)C1=CC=CC=C1 OYSQUGVVMMVTHE-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 230000003902 lesion Effects 0.000 claims description 2
- HCXMWFUMXGBEQA-UHFFFAOYSA-N methyl 4-[[(5-acetyl-2-oxo-1h-indol-3-ylidene)-(2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino]butanoate Chemical compound O1CCOC2=CC(C(=C3C4=CC(=CC=C4NC3=O)C(C)=O)NCCCC(=O)OC)=CC=C21 HCXMWFUMXGBEQA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- FSQQJBYLRCHDQO-UHFFFAOYSA-N n-[3-[[(5-acetyl-2-oxo-1h-indol-3-ylidene)-phenylmethyl]amino]propyl]methanesulfonamide Chemical compound C12=CC(C(=O)C)=CC=C2NC(=O)C1=C(NCCCNS(C)(=O)=O)C1=CC=CC=C1 FSQQJBYLRCHDQO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 2
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims 1
- 239000003701 inert diluent Substances 0.000 claims 1
- 201000001119 neuropathy Diseases 0.000 claims 1
- 230000007823 neuropathy Effects 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 235000005985 organic acids Nutrition 0.000 claims 1
- 208000033808 peripheral neuropathy Diseases 0.000 claims 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 claims 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 abstract 7
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 abstract 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract 2
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 abstract 2
- 125000004434 sulfur atom Chemical group 0.000 abstract 2
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 abstract 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 abstract 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 1
- 125000002993 cycloalkylene group Chemical group 0.000 abstract 1
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 228
- 238000001819 mass spectrum Methods 0.000 description 87
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 66
- 239000000741 silica gel Substances 0.000 description 60
- 229910002027 silica gel Inorganic materials 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- OGDZTLONCPVKCE-UHFFFAOYSA-N 1,5-diacetyl-3h-indol-2-one Chemical compound CC(=O)C1=CC=C2N(C(=O)C)C(=O)CC2=C1 OGDZTLONCPVKCE-UHFFFAOYSA-N 0.000 description 41
- 102000001267 GSK3 Human genes 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000013543 active substance Substances 0.000 description 17
- 235000002639 sodium chloride Nutrition 0.000 description 17
- 239000003112 inhibitor Substances 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical group C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 9
- 239000012141 concentrate Substances 0.000 description 9
- 239000008103 glucose Substances 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- 229920002527 Glycogen Polymers 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 229940096919 glycogen Drugs 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000002585 base Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 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 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 108010001483 Glycogen Synthase Proteins 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008298 dragée Substances 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 102000013498 tau Proteins Human genes 0.000 description 5
- 108010026424 tau Proteins Proteins 0.000 description 5
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 4
- CMULJQRPNMIROG-UHFFFAOYSA-N 5-acetyl-3-[1,3-benzodioxol-5-yl-[3-(methylamino)propylamino]methylidene]-1h-indol-2-one Chemical compound C1=C2OCOC2=CC(C(=C2C3=CC(=CC=C3NC2=O)C(C)=O)NCCCNC)=C1 CMULJQRPNMIROG-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 229960001729 voglibose Drugs 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
- C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61P25/18—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
- A61P25/28—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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- C07D403/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004012068A DE102004012068A1 (de) | 2004-03-12 | 2004-03-12 | Neue alkyl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel |
| DE102004012068 | 2004-03-12 | ||
| US55947104P | 2004-04-05 | 2004-04-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2320905T3 true ES2320905T3 (es) | 2009-05-29 |
Family
ID=34987190
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES05715811T Expired - Lifetime ES2320905T3 (es) | 2004-03-12 | 2005-03-05 | Nuevas 5-acilindolinonas con contenido en alquilo, su preparacion y su uso como medicamentos. |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US7560480B2 (enExample) |
| EP (1) | EP1727799B1 (enExample) |
| JP (1) | JP2007528883A (enExample) |
| AR (1) | AR048009A1 (enExample) |
| AT (1) | ATE420072T1 (enExample) |
| CA (1) | CA2559139A1 (enExample) |
| DE (2) | DE102004012068A1 (enExample) |
| ES (1) | ES2320905T3 (enExample) |
| UY (1) | UY28804A1 (enExample) |
| WO (1) | WO2005087727A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2348099T3 (es) * | 2005-06-10 | 2010-11-30 | Merck Patent Gmbh | Oxindoles como inhibidores de cinasa. |
| JP2010500300A (ja) | 2006-08-08 | 2010-01-07 | サノフィ−アベンティス | アリールアミノアリール−アルキル−置換イミダゾリジン−２，４−ジオン、それらの製造法、それらの化合物を含有する薬剤、およびそれらの使用 |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| AU2009207861A1 (en) * | 2008-01-25 | 2009-07-30 | Boehringer Ingelheim International Gmbh | Process for the manufacture of a 6-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene derivative |
| WO2010003624A2 (en) | 2008-07-09 | 2010-01-14 | Sanofi-Aventis | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| SG178880A1 (en) | 2009-08-26 | 2012-04-27 | Sanofi Sa | Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| US8809324B2 (en) | 2011-03-08 | 2014-08-19 | Sanofi | Substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
| US8846666B2 (en) | 2011-03-08 | 2014-09-30 | Sanofi | Oxathiazine derivatives which are substituted with benzyl or heteromethylene groups, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| EP2683703B1 (de) | 2011-03-08 | 2015-05-27 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120055A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683698B1 (de) | 2011-03-08 | 2017-10-04 | Sanofi | Mit adamantan- oder noradamantan substituierte benzyl-oxathiazinderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US9492430B2 (en) * | 2011-11-14 | 2016-11-15 | Ligand Pharmaceuticals, Incorporated | Methods and compositions associated with the granulocyte colony-stimulating factor receptor |
| BR112021002207A2 (pt) | 2018-08-10 | 2021-05-04 | Diapin Therapeutics, Llc | tri-peptídeos e tratamento de distúrbios metabólicos, cardiovasculares e inflamatórios |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19949209A1 (de) * | 1999-10-13 | 2001-04-19 | Boehringer Ingelheim Pharma | In 5-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE102004012069A1 (de) | 2004-03-12 | 2005-09-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue aryl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel |
-
2004
- 2004-03-12 DE DE102004012068A patent/DE102004012068A1/de not_active Withdrawn
-
2005
- 2005-03-05 EP EP05715811A patent/EP1727799B1/de not_active Expired - Lifetime
- 2005-03-05 ES ES05715811T patent/ES2320905T3/es not_active Expired - Lifetime
- 2005-03-05 WO PCT/EP2005/002406 patent/WO2005087727A1/de not_active Ceased
- 2005-03-05 JP JP2007502261A patent/JP2007528883A/ja active Pending
- 2005-03-05 AT AT05715811T patent/ATE420072T1/de not_active IP Right Cessation
- 2005-03-05 CA CA002559139A patent/CA2559139A1/en not_active Abandoned
- 2005-03-05 DE DE502005006424T patent/DE502005006424D1/de not_active Expired - Fee Related
- 2005-03-10 US US11/077,399 patent/US7560480B2/en active Active
- 2005-03-11 UY UY28804A patent/UY28804A1/es not_active Application Discontinuation
- 2005-03-11 AR ARP050100966A patent/AR048009A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20050209302A1 (en) | 2005-09-22 |
| EP1727799B1 (de) | 2009-01-07 |
| DE502005006424D1 (de) | 2009-02-26 |
| JP2007528883A (ja) | 2007-10-18 |
| CA2559139A1 (en) | 2005-09-22 |
| UY28804A1 (es) | 2005-10-31 |
| DE102004012068A1 (de) | 2005-09-29 |
| WO2005087727A1 (de) | 2005-09-22 |
| AR048009A1 (es) | 2006-03-15 |
| US7560480B2 (en) | 2009-07-14 |
| EP1727799A1 (de) | 2006-12-06 |
| ATE420072T1 (de) | 2009-01-15 |
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