JP2006501273A5 - - Google Patents
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- JP2006501273A5 JP2006501273A5 JP2004537020A JP2004537020A JP2006501273A5 JP 2006501273 A5 JP2006501273 A5 JP 2006501273A5 JP 2004537020 A JP2004537020 A JP 2004537020A JP 2004537020 A JP2004537020 A JP 2004537020A JP 2006501273 A5 JP2006501273 A5 JP 2006501273A5
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- Japan
- Prior art keywords
- group
- alkyl
- amino
- substituted
- alkoxy
- Prior art date
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- -1 C 1-3 -alkoxy Chemical group 0.000 claims 106
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 98
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 70
- 125000006842 cycloalkyleneimino group Chemical group 0.000 claims 51
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 50
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 38
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims 34
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 34
- 125000000217 alkyl group Chemical group 0.000 claims 29
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 27
- 150000001875 compounds Chemical class 0.000 claims 26
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 25
- 125000004434 sulfur atom Chemical group 0.000 claims 24
- 229910052717 sulfur Inorganic materials 0.000 claims 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 19
- 229910052760 oxygen Inorganic materials 0.000 claims 19
- 239000001301 oxygen Substances 0.000 claims 19
- 125000004430 oxygen atom Chemical group O* 0.000 claims 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 18
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 17
- 229910052801 chlorine Inorganic materials 0.000 claims 17
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 15
- 229910052757 nitrogen Inorganic materials 0.000 claims 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 14
- 229910052731 fluorine Inorganic materials 0.000 claims 14
- 239000011737 fluorine Substances 0.000 claims 14
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 12
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 11
- 239000000460 chlorine Substances 0.000 claims 11
- 125000004076 pyridyl group Chemical group 0.000 claims 11
- 150000003839 salts Chemical class 0.000 claims 11
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 10
- 125000003277 amino group Chemical group 0.000 claims 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims 10
- 125000001072 heteroaryl group Chemical group 0.000 claims 10
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims 9
- 150000001721 carbon Chemical group 0.000 claims 9
- 229910052799 carbon Inorganic materials 0.000 claims 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 8
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 8
- 229910052794 bromium Inorganic materials 0.000 claims 8
- 125000004432 carbon atom Chemical group C* 0.000 claims 8
- NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical group N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 8
- 229910052740 iodine Inorganic materials 0.000 claims 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 6
- 125000003545 alkoxy group Chemical group 0.000 claims 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims 6
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 125000001841 imino group Chemical group [H]N=* 0.000 claims 6
- 239000000651 prodrug Substances 0.000 claims 6
- 229940002612 prodrug Drugs 0.000 claims 6
- 125000006602 (C1-C3) alkylsulfonylamino group Chemical group 0.000 claims 5
- 125000003282 alkyl amino group Chemical group 0.000 claims 5
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 5
- 125000006239 protecting group Chemical group 0.000 claims 5
- 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 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 4
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 4
- 125000004122 cyclic group Chemical group 0.000 claims 4
- 125000002993 cycloalkylene group Chemical group 0.000 claims 4
- 150000003951 lactams Chemical group 0.000 claims 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 4
- 239000007790 solid phase Substances 0.000 claims 4
- 125000006603 (C1-C3) alkylaminosulfonyl group Chemical group 0.000 claims 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 3
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 125000002950 monocyclic group Chemical group 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims 3
- 125000001425 triazolyl group Chemical group 0.000 claims 3
- JTTYBEQWOFZMFP-RQZHXJHFSA-N (3z)-3-[1,3-benzodioxol-5-yl-[4-[(4-methylpiperazin-1-yl)methyl]anilino]methylidene]-6-chloro-1h-indol-2-one Chemical compound C1CN(C)CCN1CC(C=C1)=CC=C1N\C(C=1C=C2OCOC2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O JTTYBEQWOFZMFP-RQZHXJHFSA-N 0.000 claims 2
- KWFUYECTBFRIRG-IZHYLOQSSA-N (3z)-3-[1,3-benzodioxol-5-yl-[4-[[ethyl(methyl)amino]methyl]anilino]methylidene]-6-chloro-1h-indol-2-one Chemical compound C1=CC(CN(C)CC)=CC=C1N\C(C=1C=C2OCOC2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O KWFUYECTBFRIRG-IZHYLOQSSA-N 0.000 claims 2
- KSJXPOZSSRPFPB-IZHYLOQSSA-N (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-(ethylaminomethyl)anilino]methylidene]-6-fluoro-1h-indol-2-one Chemical compound C1=CC(CNCC)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(F)C=C2NC\1=O KSJXPOZSSRPFPB-IZHYLOQSSA-N 0.000 claims 2
- ODEQWQXGCAYNQS-IZHYLOQSSA-N (3z)-6-chloro-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-[(dimethylamino)methyl]anilino]methylidene]-1h-indol-2-one Chemical compound C1=CC(CN(C)C)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O ODEQWQXGCAYNQS-IZHYLOQSSA-N 0.000 claims 2
- YAJULHYYDWJESD-IZHYLOQSSA-N (3z)-6-chloro-3-[[4-[(dimethylamino)methyl]anilino]-(1-methylbenzimidazol-5-yl)methylidene]-1h-indol-2-one Chemical compound C1=CC(CN(C)C)=CC=C1N\C(C=1C=C2N=CN(C)C2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O YAJULHYYDWJESD-IZHYLOQSSA-N 0.000 claims 2
- LKURCHRXPCDQMT-IZHYLOQSSA-N (3z)-6-fluoro-3-[(1-methylbenzimidazol-5-yl)-[4-(1,2,4-triazol-1-ylmethyl)anilino]methylidene]-1h-indol-2-one Chemical compound C=1C=C2N(C)C=NC2=CC=1C(=C\1C2=CC=C(F)C=C2NC/1=O)\NC(C=C1)=CC=C1CN1C=NC=N1 LKURCHRXPCDQMT-IZHYLOQSSA-N 0.000 claims 2
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 claims 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 2
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 2
- 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 claims 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 2
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical group OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 claims 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 125000002619 bicyclic group Chemical group 0.000 claims 2
- 239000000969 carrier Substances 0.000 claims 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- IXJISIDVDXYLTI-RQZHXJHFSA-N methyl (3z)-3-[1,3-benzodioxol-5-yl-[4-(diethylaminomethyl)anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound C1=CC(CN(CC)CC)=CC=C1N\C(C=1C=C2OCOC2=CC=1)=C/1C2=CC=C(C(=O)OC)C=C2NC\1=O IXJISIDVDXYLTI-RQZHXJHFSA-N 0.000 claims 2
- YDJNGVGZHOABKD-IZHYLOQSSA-N methyl (3z)-3-[1,3-benzodioxol-5-yl-[4-[(dimethylamino)methyl]anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCOC2=CC=1)\NC1=CC=C(CN(C)C)C=C1 YDJNGVGZHOABKD-IZHYLOQSSA-N 0.000 claims 2
- XUKMQAUQPSBMPQ-RQZHXJHFSA-N methyl (3z)-3-[1,3-benzodioxol-5-yl-[4-[2-(dimethylamino)ethyl-methylcarbamoyl]anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCOC2=CC=1)\NC1=CC=C(C(=O)N(C)CCN(C)C)C=C1 XUKMQAUQPSBMPQ-RQZHXJHFSA-N 0.000 claims 2
- VZCBAERILCJERL-QPLCGJKRSA-N methyl (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-(ethylaminomethyl)anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound C1=CC(CNCC)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(C(=O)OC)C=C2NC\1=O VZCBAERILCJERL-QPLCGJKRSA-N 0.000 claims 2
- DJNBIJXUUAGOGV-DQSJHHFOSA-N methyl (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-(pyrrolidin-1-ylmethyl)anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCCOC2=CC=1)\NC(C=C1)=CC=C1CN1CCCC1 DJNBIJXUUAGOGV-DQSJHHFOSA-N 0.000 claims 2
- ISQFIECKXMSFOU-ZIADKAODSA-N methyl (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-[(4-methylpiperazin-1-yl)methyl]anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCCOC2=CC=1)\NC(C=C1)=CC=C1CN1CCN(C)CC1 ISQFIECKXMSFOU-ZIADKAODSA-N 0.000 claims 2
- HPODJPLRFPIIGJ-QPLCGJKRSA-N methyl (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-[(dimethylamino)methyl]anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCCOC2=CC=1)\NC1=CC=C(CN(C)C)C=C1 HPODJPLRFPIIGJ-QPLCGJKRSA-N 0.000 claims 2
- MXWVZQNZTKXKKO-DQSJHHFOSA-N methyl (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-[2-(dimethylamino)ethyl-methylcarbamoyl]anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCCOC2=CC=1)\NC1=CC=C(C(=O)N(C)CCN(C)C)C=C1 MXWVZQNZTKXKKO-DQSJHHFOSA-N 0.000 claims 2
- PAIOVUWLCWJFCV-DQSJHHFOSA-N methyl (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-[2-(dimethylamino)ethyl-methylsulfonylamino]anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCCOC2=CC=1)\NC1=CC=C(N(CCN(C)C)S(C)(=O)=O)C=C1 PAIOVUWLCWJFCV-DQSJHHFOSA-N 0.000 claims 2
- AOPHCTKRYHULCH-ZIADKAODSA-N methyl (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-[3-(dimethylamino)propyl-methylcarbamoyl]anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCCOC2=CC=1)\NC1=CC=C(C(=O)N(C)CCCN(C)C)C=C1 AOPHCTKRYHULCH-ZIADKAODSA-N 0.000 claims 2
- SXWOVUCGBCAXQL-DQSJHHFOSA-N methyl (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-[[2-(dimethylamino)acetyl]-methylamino]anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCCOC2=CC=1)\NC1=CC=C(N(C)C(=O)CN(C)C)C=C1 SXWOVUCGBCAXQL-DQSJHHFOSA-N 0.000 claims 2
- ODQMWYRZGUKRRX-KTMFPKCZSA-N methyl (3z)-3-[2,3-dihydro-1,4-benzodioxin-6-yl-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCCOC2=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 ODQMWYRZGUKRRX-KTMFPKCZSA-N 0.000 claims 2
- NLWJTHWHZRNPHE-ZIADKAODSA-N methyl (3z)-3-[[4-[acetyl-[2-(dimethylamino)ethyl]amino]anilino]-(2,3-dihydro-1,4-benzodioxin-6-yl)methylidene]-2-oxo-1h-indole-6-carboxylate Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=C2OCCOC2=CC=1)\NC1=CC=C(N(CCN(C)C)C(C)=O)C=C1 NLWJTHWHZRNPHE-ZIADKAODSA-N 0.000 claims 2
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims 2
- YIFIFSOAJPIGIJ-DQSJHHFOSA-N n-[4-[[(z)-(6-chloro-2-oxo-1h-indol-3-ylidene)-(2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino]phenyl]-n-[2-(dimethylamino)ethyl]acetamide Chemical compound C1=CC(N(C(C)=O)CCN(C)C)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O YIFIFSOAJPIGIJ-DQSJHHFOSA-N 0.000 claims 2
- LAUNLLGATPLKLE-RQZHXJHFSA-N n-[4-[[(z)-(6-chloro-2-oxo-1h-indol-3-ylidene)-(2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino]phenyl]-n-[2-(dimethylamino)ethyl]methanesulfonamide Chemical compound C1=CC(N(CCN(C)C)S(C)(=O)=O)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O LAUNLLGATPLKLE-RQZHXJHFSA-N 0.000 claims 2
- LMCVWVYZMQAGJZ-ZIADKAODSA-N n-[4-[[(z)-(6-chloro-2-oxo-1h-indol-3-ylidene)-(2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino]phenyl]-n-[2-(dimethylamino)ethyl]propanamide Chemical compound C1=CC(N(CCN(C)C)C(=O)CC)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O LMCVWVYZMQAGJZ-ZIADKAODSA-N 0.000 claims 2
- DVEVDZVUEOLBQR-ZIADKAODSA-N n-[4-[[(z)-(6-chloro-2-oxo-1h-indol-3-ylidene)-(2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino]phenyl]-n-[3-(dimethylamino)propyl]acetamide Chemical compound C1=CC(N(C(C)=O)CCCN(C)C)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O DVEVDZVUEOLBQR-ZIADKAODSA-N 0.000 claims 2
- JDSVKRGOXWZTOV-FLWNBWAVSA-N n-[4-[[(z)-(6-chloro-2-oxo-1h-indol-3-ylidene)-(2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino]phenyl]-n-[3-(dimethylamino)propyl]propanamide Chemical compound C1=CC(N(CCCN(C)C)C(=O)CC)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O JDSVKRGOXWZTOV-FLWNBWAVSA-N 0.000 claims 2
- NGHNVCYNFAUQID-ZIADKAODSA-N n-[4-[[(z)-1,3-benzodioxol-5-yl-(6-chloro-2-oxo-1h-indol-3-ylidene)methyl]amino]phenyl]-n-methyl-2-(4-methylpiperazin-1-yl)acetamide Chemical compound C=1C=C(N\C(=C/2C3=CC=C(Cl)C=C3NC\2=O)C=2C=C3OCOC3=CC=2)C=CC=1N(C)C(=O)CN1CCN(C)CC1 NGHNVCYNFAUQID-ZIADKAODSA-N 0.000 claims 2
- NVIHLCZLWCZJBD-DQSJHHFOSA-N n-[4-[[(z)-2,3-dihydro-1,4-benzodioxin-6-yl-(6-fluoro-2-oxo-1h-indol-3-ylidene)methyl]amino]phenyl]-3-(dimethylamino)-n-methylpropanamide Chemical compound C1=CC(N(C)C(=O)CCN(C)C)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(F)C=C2NC\1=O NVIHLCZLWCZJBD-DQSJHHFOSA-N 0.000 claims 2
- MFYUMLZIDDEUAL-DQSJHHFOSA-N n-[4-[[(z)-2,3-dihydro-1,4-benzodioxin-6-yl-(6-fluoro-2-oxo-1h-indol-3-ylidene)methyl]amino]phenyl]-n-[2-(dimethylamino)ethyl]acetamide Chemical compound C1=CC(N(C(C)=O)CCN(C)C)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(F)C=C2NC\1=O MFYUMLZIDDEUAL-DQSJHHFOSA-N 0.000 claims 2
- VENAFAWDQVOHSC-RQZHXJHFSA-N n-[4-[[(z)-2,3-dihydro-1,4-benzodioxin-6-yl-(6-fluoro-2-oxo-1h-indol-3-ylidene)methyl]amino]phenyl]-n-[2-(dimethylamino)ethyl]methanesulfonamide Chemical compound C1=CC(N(CCN(C)C)S(C)(=O)=O)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(F)C=C2NC\1=O VENAFAWDQVOHSC-RQZHXJHFSA-N 0.000 claims 2
- TUSQYMMJEGRGEE-ZIADKAODSA-N n-[4-[[(z)-2,3-dihydro-1,4-benzodioxin-6-yl-(6-fluoro-2-oxo-1h-indol-3-ylidene)methyl]amino]phenyl]-n-[2-(dimethylamino)ethyl]propanamide Chemical compound C1=CC(N(CCN(C)C)C(=O)CC)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(F)C=C2NC\1=O TUSQYMMJEGRGEE-ZIADKAODSA-N 0.000 claims 2
- HRPALFYCQQDKHS-FLWNBWAVSA-N n-[4-[[(z)-2,3-dihydro-1,4-benzodioxin-6-yl-(6-fluoro-2-oxo-1h-indol-3-ylidene)methyl]amino]phenyl]-n-[3-(dimethylamino)propyl]propanamide Chemical compound C1=CC(N(CCCN(C)C)C(=O)CC)=CC=C1N\C(C=1C=C2OCCOC2=CC=1)=C/1C2=CC=C(F)C=C2NC\1=O HRPALFYCQQDKHS-FLWNBWAVSA-N 0.000 claims 2
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 claims 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 2
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims 2
- 125000006850 spacer group Chemical group 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- NWXVVFGMDWXASW-VHXPQNKSSA-N (3z)-3-[1,3-benzodioxol-5-yl-[4-[(dimethylamino)methyl]anilino]methylidene]-6-chloro-1h-indol-2-one Chemical compound C1=CC(CN(C)C)=CC=C1N\C(C=1C=C2OCOC2=CC=1)=C/1C2=CC=C(Cl)C=C2NC\1=O NWXVVFGMDWXASW-VHXPQNKSSA-N 0.000 claims 1
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims 1
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 claims 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims 1
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims 1
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical group OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 230000009435 amidation Effects 0.000 claims 1
- 238000007112 amidation reaction Methods 0.000 claims 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims 1
- 230000004663 cell proliferation Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000032050 esterification Effects 0.000 claims 1
- 238000005886 esterification reaction Methods 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 239000012948 isocyanate Substances 0.000 claims 1
- 150000002513 isocyanates Chemical class 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- WWULUXRSBUVGLP-FLWNBWAVSA-N n-[4-[[(z)-(6-chloro-2-oxo-1h-indol-3-ylidene)-quinoxalin-6-ylmethyl]amino]phenyl]-n-methyl-2-(4-methylpiperazin-1-yl)acetamide Chemical compound C=1C=C(N\C(=C/2C3=CC=C(Cl)C=C3NC\2=O)C=2C=C3N=CC=NC3=CC=2)C=CC=1N(C)C(=O)CN1CCN(C)CC1 WWULUXRSBUVGLP-FLWNBWAVSA-N 0.000 claims 1
- ORCORJGKVRYZMU-ZIADKAODSA-N n-[4-[[(z)-1,3-benzodioxol-5-yl-(6-bromo-2-oxo-1h-indol-3-ylidene)methyl]amino]phenyl]-n-methyl-2-(4-methylpiperazin-1-yl)acetamide Chemical compound C=1C=C(N\C(=C/2C3=CC=C(Br)C=C3NC\2=O)C=2C=C3OCOC3=CC=2)C=CC=1N(C)C(=O)CN1CCN(C)CC1 ORCORJGKVRYZMU-ZIADKAODSA-N 0.000 claims 1
- AEKCMFSCXYBMTH-ZIADKAODSA-N n-[4-[[(z)-1,3-benzodioxol-5-yl-(6-fluoro-2-oxo-1h-indol-3-ylidene)methyl]amino]phenyl]-n-methyl-2-(4-methylpiperazin-1-yl)acetamide Chemical compound C=1C=C(N\C(=C/2C3=CC=C(F)C=C3NC\2=O)C=2C=C3OCOC3=CC=2)C=CC=1N(C)C(=O)CN1CCN(C)CC1 AEKCMFSCXYBMTH-ZIADKAODSA-N 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 235000005985 organic acids Nutrition 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 238000006722 reduction reaction Methods 0.000 claims 1
- 238000005932 reductive alkylation reaction Methods 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 230000006103 sulfonylation Effects 0.000 claims 1
- 238000005694 sulfonylation reaction Methods 0.000 claims 1
- 125000005505 thiomorpholino group Chemical group 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2002142350 DE10242350A1 (de) | 2002-09-12 | 2002-09-12 | Heterocyclisch substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE10252969A DE10252969A1 (de) | 2002-11-14 | 2002-11-14 | Heterocyclisch substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| PCT/EP2003/009978 WO2004026829A2 (de) | 2002-09-12 | 2003-09-09 | Heterocyclisch substituierte indolinone und deren verwendung als rezeptor-tyrosinkinasen inhibitoren |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006501273A JP2006501273A (ja) | 2006-01-12 |
| JP2006501273A5 true JP2006501273A5 (https=) | 2006-02-23 |
Family
ID=32031471
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004537020A Pending JP2006501273A (ja) | 2002-09-12 | 2003-09-09 | ヘテロ環置換インドリノン、その製法及び薬物としてのその使用 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7148249B2 (https=) |
| EP (1) | EP1551830B1 (https=) |
| JP (1) | JP2006501273A (https=) |
| AR (1) | AR041194A1 (https=) |
| AT (1) | ATE427947T1 (https=) |
| AU (1) | AU2003273842A1 (https=) |
| CA (1) | CA2498781A1 (https=) |
| DE (1) | DE50311397D1 (https=) |
| ES (1) | ES2324710T3 (https=) |
| PE (1) | PE20041080A1 (https=) |
| TW (1) | TW200407125A (https=) |
| WO (1) | WO2004026829A2 (https=) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6982260B1 (en) | 1999-11-22 | 2006-01-03 | Warner-Lambert Company | Quinazolines and their use for inhibiting cyclin-dependent kinase enzymes |
| JP4564713B2 (ja) | 2000-11-01 | 2010-10-20 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | 窒素性複素環式化合物、ならびに窒素性複素環式化合物およびその中間体を作製するための方法 |
| US20040204458A1 (en) * | 2002-08-16 | 2004-10-14 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Use of Lck inhibitors for treatment of immunologic diseases |
| MXPA06007017A (es) | 2003-12-18 | 2006-08-31 | Janssen Pharmaceutica Nv | Derivados de pirido y pirimidopirimidina como agentes antiproliferativos. |
| KR100629713B1 (ko) * | 2004-04-10 | 2006-09-29 | (주)아모레퍼시픽 | 펜타에리스리톨 유도체와 이의 제조방법, 및 이를포함하는 액정베이스 |
| NI200700147A (es) | 2004-12-08 | 2019-05-10 | Janssen Pharmaceutica Nv | Derivados de quinazolina inhibidores de cinasas dirigidos a multip |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| JP2009542778A (ja) | 2006-07-13 | 2009-12-03 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｍｔｋｉキナゾリン誘導体 |
| JP2010502741A (ja) * | 2006-09-11 | 2010-01-28 | キュリス，インコーポレイテッド | Ｐｔｋインヒビターとしての亜鉛結合部分を含む置換２−インドリノン |
| CA2687909C (en) | 2007-06-21 | 2015-09-15 | Janssen Pharmaceutica Nv | Indolin-2-ones and aza-indolin-2-ones |
| AU2008281849B2 (en) | 2007-07-27 | 2013-11-28 | Janssen Pharmaceutica Nv | Pyrrolopyrimidines |
| UY31506A1 (es) * | 2007-12-03 | 2009-08-03 | Derivados de indolinona y procedimiento para su preparacion | |
| RU2525114C2 (ru) * | 2007-12-03 | 2014-08-10 | Бёрингер Ингельхайм Интернациональ Гмбх | Способ получения производного индолинона |
| EP2235004A4 (en) * | 2007-12-21 | 2011-05-04 | Univ Health Network | INDAZOLYL, BENZIMIDAZOLYL, BENZOTRIAZOLYL-SUBSTITUTED INDOLUND DERIVATIVES AS A KINASE-HEMMER FOR CANCER TREATMENT |
| ME02273B (me) * | 2008-06-06 | 2016-02-20 | Boehringer Ingelheim Int | Farmaceutska kombinacija |
| AR072538A1 (es) * | 2008-07-29 | 2010-09-01 | Boehringer Ingelheim Int | Derivados de indolinonas, composiciones farmacéuticas y usos |
| ES2465971T3 (es) | 2009-04-06 | 2014-06-09 | University Health Network | Inhibidores de quinasa y método para tratar cáncer con los mismos |
| SI2556071T1 (sl) | 2010-04-06 | 2016-12-30 | University Health Network | Kinazni inhibitorji in njihova uporaba pri zdravljenju raka |
| WO2012048411A1 (en) * | 2010-10-13 | 2012-04-19 | University Health Network | Plk-4 inhibitors and method of treating cancer with same |
| CN103848814B (zh) * | 2012-12-06 | 2016-08-17 | 山东亨利医药科技有限责任公司 | 作为酪氨酸激酶抑制剂的取代吲哚满酮衍生物 |
| WO2014086102A1 (zh) * | 2012-12-06 | 2014-06-12 | 山东亨利医药科技有限责任公司 | 作为酪氨酸激酶抑制剂的吲哚满酮衍生物 |
| EP3012248B1 (en) * | 2013-06-20 | 2019-09-11 | Institute of Radiation Medicine, Academy of Military Medical Sciences, People's Liberation Army of China | Substance having tyrosine kinase inhibitory activity and preparation method and use thereof |
| WO2015054781A1 (en) | 2013-10-18 | 2015-04-23 | University Health Network | Treatment for pancreatic cancer |
| WO2018124001A1 (ja) | 2016-12-27 | 2018-07-05 | 国立研究開発法人理化学研究所 | Ｂｍｐシグナル阻害化合物 |
| CN112174943A (zh) * | 2019-07-03 | 2021-01-05 | 四川大学 | 一种吲哚-2-酮类化合物在制备防治口腔细菌产品中的用途 |
| CN114213396B (zh) * | 2022-01-27 | 2023-03-24 | 深圳市乐土生物医药有限公司 | 一种吲哚-2-酮类化合物及其制备方法与用途 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20010216A2 (en) * | 1998-09-25 | 2002-04-30 | Boehringer Ingelheim Pharma | New substituted indolinones, their preparation and their use as medicaments |
| CA2381821A1 (en) | 1999-08-27 | 2001-03-08 | Boehringer Ingelheim Pharma Kg | Substituted indolinones, their manufacture and their use as medicaments |
| US6762180B1 (en) * | 1999-10-13 | 2004-07-13 | Boehringer Ingelheim Pharma Kg | Substituted indolines which inhibit receptor tyrosine kinases |
| UA75054C2 (uk) | 1999-10-13 | 2006-03-15 | Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг | Заміщені в положенні 6 індолінони, їх одержання та їх застосування як лікарського засобу |
| DE19949209A1 (de) | 1999-10-13 | 2001-04-19 | Boehringer Ingelheim Pharma | In 5-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE10117204A1 (de) * | 2001-04-06 | 2002-10-10 | Boehringer Ingelheim Pharma | In 6-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
-
2003
- 2003-09-05 US US10/656,863 patent/US7148249B2/en not_active Expired - Lifetime
- 2003-09-09 CA CA002498781A patent/CA2498781A1/en not_active Abandoned
- 2003-09-09 DE DE50311397T patent/DE50311397D1/de not_active Expired - Lifetime
- 2003-09-09 EP EP03757806A patent/EP1551830B1/de not_active Expired - Lifetime
- 2003-09-09 AT AT03757806T patent/ATE427947T1/de not_active IP Right Cessation
- 2003-09-09 ES ES03757806T patent/ES2324710T3/es not_active Expired - Lifetime
- 2003-09-09 JP JP2004537020A patent/JP2006501273A/ja active Pending
- 2003-09-09 AU AU2003273842A patent/AU2003273842A1/en not_active Abandoned
- 2003-09-09 WO PCT/EP2003/009978 patent/WO2004026829A2/de not_active Ceased
- 2003-09-10 PE PE2003000915A patent/PE20041080A1/es not_active Application Discontinuation
- 2003-09-10 TW TW092125060A patent/TW200407125A/zh unknown
- 2003-09-12 AR ARP030103306A patent/AR041194A1/es unknown
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