JP2015504093A5 - - Google Patents
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- Publication number
- JP2015504093A5 JP2015504093A5 JP2014553451A JP2014553451A JP2015504093A5 JP 2015504093 A5 JP2015504093 A5 JP 2015504093A5 JP 2014553451 A JP2014553451 A JP 2014553451A JP 2014553451 A JP2014553451 A JP 2014553451A JP 2015504093 A5 JP2015504093 A5 JP 2015504093A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- ylamino
- pyrazol
- indol
- pyrimidin
- 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.)
- Granted
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- -1 amino, hydroxy Chemical group 0.000 claims 25
- 150000001875 compounds Chemical class 0.000 claims 15
- 125000005843 halogen group Chemical group 0.000 claims 15
- 125000003118 aryl group Chemical group 0.000 claims 13
- 229920006395 saturated elastomer Polymers 0.000 claims 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims 10
- 125000002950 monocyclic group Chemical group 0.000 claims 10
- 229910052757 nitrogen Inorganic materials 0.000 claims 10
- 125000005842 heteroatom Chemical group 0.000 claims 8
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- 125000001072 heteroaryl group Chemical group 0.000 claims 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 7
- 125000001188 haloalkyl group Chemical group 0.000 claims 6
- 125000003545 alkoxy group Chemical group 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 4
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims 2
- QTNLJTSGFKCIKB-UHFFFAOYSA-N cyclopropyl-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1,2-dimethylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=C(C)N(C)C4=CC=3)N=CC=2)C=C1CN1CC(O)C1 QTNLJTSGFKCIKB-UHFFFAOYSA-N 0.000 claims 2
- ZRYVEASTNWHZKR-ZRZAMGCNSA-N cyclopropyl-[5-[[4-[4-[[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1,2-dimethylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=C(C)N(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 ZRYVEASTNWHZKR-ZRZAMGCNSA-N 0.000 claims 2
- 230000003325 follicular Effects 0.000 claims 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 239000001301 oxygen Chemical group 0.000 claims 2
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 150000003457 sulfones Chemical group 0.000 claims 2
- 150000003462 sulfoxides Chemical group 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 239000011593 sulfur Chemical group 0.000 claims 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 2
- BDZYVSQZYKURPZ-RBUKOAKNSA-N (3r,5s)-5-(hydroxymethyl)-1-[[3-methyl-1-[2-[(1-methyl-3-methylsulfonylindol-5-yl)amino]pyrimidin-4-yl]pyrazol-4-yl]methyl]pyrrolidin-3-ol Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(=CN(C)C4=CC=3)S(C)(=O)=O)N=CC=2)C=C1CN1C[C@H](O)C[C@H]1CO BDZYVSQZYKURPZ-RBUKOAKNSA-N 0.000 claims 1
- JCZPOYAMKJFOLA-ZXZARUISSA-N (3s,4r)-pyrrolidine-3,4-diol Chemical compound O[C@H]1CNC[C@H]1O JCZPOYAMKJFOLA-ZXZARUISSA-N 0.000 claims 1
- LVDAOOBTKGLDAK-UHFFFAOYSA-N 1-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound C1=C2C(C(=O)C)=CN(C)C2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1CC(O)C1 LVDAOOBTKGLDAK-UHFFFAOYSA-N 0.000 claims 1
- FLGSFJVMDOPSIH-GOSISDBHSA-N 1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound C1=C2C(C(=O)C)=CNC2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1CC[C@@H](O)C1 FLGSFJVMDOPSIH-GOSISDBHSA-N 0.000 claims 1
- QSHBGWBTDPULOV-BGYRXZFFSA-N 1-[5-[[4-[4-[[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2,2-trifluoroethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 QSHBGWBTDPULOV-BGYRXZFFSA-N 0.000 claims 1
- BOAWZTDHVMBMEN-KDURUIRLSA-N 1-[5-[[4-[4-[[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]-2,2,2-trifluoroethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 BOAWZTDHVMBMEN-KDURUIRLSA-N 0.000 claims 1
- RBKBIFWYNLXUJN-KDURUIRLSA-N 1-[5-[[4-[4-[[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]-2,2-difluoroethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 RBKBIFWYNLXUJN-KDURUIRLSA-N 0.000 claims 1
- LHGNCEUWLNJOPN-ZRZAMGCNSA-N 1-[5-[[4-[4-[[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2-dimethylpropan-1-one Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(C)(C)C)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 LHGNCEUWLNJOPN-ZRZAMGCNSA-N 0.000 claims 1
- WXWUQOPWCPNTJP-ZRZAMGCNSA-N 1-[5-[[4-[4-[[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2-methylpropan-1-one Chemical compound C1=C2C(C(=O)C(C)C)=CN(C)C2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1C[C@H](O)[C@H](O)C1 WXWUQOPWCPNTJP-ZRZAMGCNSA-N 0.000 claims 1
- NQRYGQAPAJNGLL-OYRHEFFESA-N 1-[5-[[4-[4-[[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound C1=C2C(C(=O)C)=CNC2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1C[C@H](O)[C@H](O)C1 NQRYGQAPAJNGLL-OYRHEFFESA-N 0.000 claims 1
- KBAODVSDRBXPFB-BJKOFHAPSA-N 1-[5-[[4-[4-[[(3s,4r)-3-hydroxy-4-methoxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2-methylpropan-1-one Chemical compound C1[C@H](O)[C@H](OC)CN1CC1=CN(C=2N=C(NC=3C=C4C(C(=O)C(C)C)=CN(C)C4=CC=3)N=CC=2)N=C1C KBAODVSDRBXPFB-BJKOFHAPSA-N 0.000 claims 1
- MUGXJGHVJPIMFQ-PMACEKPBSA-N 1-[5-[[4-[4-[[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2-difluoroethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@@H](O)C1 MUGXJGHVJPIMFQ-PMACEKPBSA-N 0.000 claims 1
- LHGNCEUWLNJOPN-GOTSBHOMSA-N 1-[5-[[4-[4-[[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2-dimethylpropan-1-one Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(C)(C)C)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@@H](O)C1 LHGNCEUWLNJOPN-GOTSBHOMSA-N 0.000 claims 1
- WXWUQOPWCPNTJP-GOTSBHOMSA-N 1-[5-[[4-[4-[[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2-methylpropan-1-one Chemical compound C1=C2C(C(=O)C(C)C)=CN(C)C2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1C[C@H](O)[C@@H](O)C1 WXWUQOPWCPNTJP-GOTSBHOMSA-N 0.000 claims 1
- RBKBIFWYNLXUJN-OALUTQOASA-N 1-[5-[[4-[4-[[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]-2,2-difluoroethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@@H](O)C1 RBKBIFWYNLXUJN-OALUTQOASA-N 0.000 claims 1
- SWRICVFADHWLJK-UHFFFAOYSA-N 1-[[3-methyl-1-[2-[(1-methyl-3-pyrrolidin-1-ylsulfonylindol-5-yl)amino]pyrimidin-4-yl]pyrazol-4-yl]methyl]azetidin-3-ol Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(=CN(C)C4=CC=3)S(=O)(=O)N3CCCC3)N=CC=2)C=C1CN1CC(O)C1 SWRICVFADHWLJK-UHFFFAOYSA-N 0.000 claims 1
- BVJHIQCBENLSSV-UHFFFAOYSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC(O)C1 BVJHIQCBENLSSV-UHFFFAOYSA-N 0.000 claims 1
- ADWAHBOJNVCGRU-UHFFFAOYSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-2,3-dihydroindol-1-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4CCN(C4=CC=3)C(=O)C(F)(F)F)N=CC=2)C=C1CN1CC(O)C1 ADWAHBOJNVCGRU-UHFFFAOYSA-N 0.000 claims 1
- QMUBTSPFECNPLS-ZWKOTPCHSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[[(2s,4r)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)C[C@H]1CO QMUBTSPFECNPLS-ZWKOTPCHSA-N 0.000 claims 1
- HNWPDSDZWHSCID-DLBZAZTESA-N 2,2,2-trifluoro-1-[5-[[4-[4-[[(2s,4r)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1C[C@H](O)C[C@H]1CO HNWPDSDZWHSCID-DLBZAZTESA-N 0.000 claims 1
- PQBYPDZGIKKGIO-MRXNPFEDSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 PQBYPDZGIKKGIO-MRXNPFEDSA-N 0.000 claims 1
- IWVWEZSFZACKGC-LEWJYISDSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[[(3s,4r)-3-hydroxy-4-methoxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound C1[C@H](O)[C@H](OC)CN1CC1=CN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CN(C)C4=CC=3)N=CC=2)N=C1C IWVWEZSFZACKGC-LEWJYISDSA-N 0.000 claims 1
- ZRDGIOZDUKGYCA-QGZVFWFLSA-N 2,2-difluoro-1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 ZRDGIOZDUKGYCA-QGZVFWFLSA-N 0.000 claims 1
- UGQOCPKHBJZKAA-MRXNPFEDSA-N 2,2-difluoro-1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 UGQOCPKHBJZKAA-MRXNPFEDSA-N 0.000 claims 1
- FFPFVVNGWCWOPW-LEWJYISDSA-N 2,2-difluoro-1-[5-[[4-[4-[[(3s,4r)-3-hydroxy-4-methoxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound C1[C@H](O)[C@H](OC)CN1CC1=CN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CN(C)C4=CC=3)N=CC=2)N=C1C FFPFVVNGWCWOPW-LEWJYISDSA-N 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- VNVRFKHKLIDRLN-UHFFFAOYSA-N 5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-n,n,1-trimethylindole-3-carboxamide Chemical compound C1=C2C(C(=O)N(C)C)=CN(C)C2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1CC(O)C1 VNVRFKHKLIDRLN-UHFFFAOYSA-N 0.000 claims 1
- 101100079984 Caenorhabditis elegans nhr-9 gene Proteins 0.000 claims 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
- 206010052178 Lymphocytic lymphoma Diseases 0.000 claims 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims 1
- 206010042971 T-cell lymphoma Diseases 0.000 claims 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims 1
- KQVUHDMIGFMKFO-UHFFFAOYSA-N [1-[2-[(1-cyclopropyl-3-methylindol-5-yl)amino]pyrimidin-4-yl]-3-methylpyrazol-4-yl]-(3-hydroxyazetidin-1-yl)methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C)=CN(C4=CC=3)C3CC3)N=CC=2)C=C1C(=O)N1CC(O)C1 KQVUHDMIGFMKFO-UHFFFAOYSA-N 0.000 claims 1
- FOMMYQUZCYYMNG-UHFFFAOYSA-N [5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1,2-dimethylindol-3-yl]-pyrrolidin-1-ylmethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)N5CCCC5)=C(C)N(C)C4=CC=3)N=CC=2)C=C1CN1CC(O)C1 FOMMYQUZCYYMNG-UHFFFAOYSA-N 0.000 claims 1
- SWHDWSNBGVEIKM-UHFFFAOYSA-N [5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-morpholin-4-ylmethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)N5CCOCC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC(O)C1 SWHDWSNBGVEIKM-UHFFFAOYSA-N 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000002393 azetidinyl group Chemical group 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- VLSXAYNYBJKZAV-JOCHJYFZSA-N cyclopropyl-[1-cyclopropyl-5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]indol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C4=CC=3)C3CC3)N=CC=2)C=C1CN1CC[C@@H](O)C1 VLSXAYNYBJKZAV-JOCHJYFZSA-N 0.000 claims 1
- AAJLSZLYZUDYIH-HSZRJFAPSA-N cyclopropyl-[1-cyclopropyl-5-[[4-[4-[[(3r)-3-methoxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]indol-3-yl]methanone Chemical compound C1[C@H](OC)CCN1CC1=CN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C4=CC=3)C3CC3)N=CC=2)N=C1C AAJLSZLYZUDYIH-HSZRJFAPSA-N 0.000 claims 1
- WPXHOAVIWQSSDK-PLQXJYEYSA-N cyclopropyl-[1-cyclopropyl-5-[[4-[4-[[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]indol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C4=CC=3)C3CC3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 WPXHOAVIWQSSDK-PLQXJYEYSA-N 0.000 claims 1
- RSTFXRMMGRWYGT-UHFFFAOYSA-N cyclopropyl-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC(O)C1 RSTFXRMMGRWYGT-UHFFFAOYSA-N 0.000 claims 1
- AROPBXPDYKPBNJ-UHFFFAOYSA-N cyclopropyl-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]indol-1-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C=CN(C4=CC=3)C(=O)C3CC3)N=CC=2)C=C1CN1CC(O)C1 AROPBXPDYKPBNJ-UHFFFAOYSA-N 0.000 claims 1
- JSFJBYKBNANORA-OAQYLSRUSA-N cyclopropyl-[5-[[4-[4-[[(3r)-3-hydroxypiperidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CCC[C@@H](O)C1 JSFJBYKBNANORA-OAQYLSRUSA-N 0.000 claims 1
- FNGJTJGYKVSXHA-HXUWFJFHSA-N cyclopropyl-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 FNGJTJGYKVSXHA-HXUWFJFHSA-N 0.000 claims 1
- VUAQDGAQHZEJRI-LJQANCHMSA-N cyclopropyl-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CNC4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 VUAQDGAQHZEJRI-LJQANCHMSA-N 0.000 claims 1
- HNSGGOLPCJWHBE-ZRZAMGCNSA-N cyclopropyl-[5-[[4-[4-[[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 HNSGGOLPCJWHBE-ZRZAMGCNSA-N 0.000 claims 1
- PHFOPTLWGQJGMW-SZPZYZBQSA-N cyclopropyl-[5-[[4-[4-[[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CNC4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 PHFOPTLWGQJGMW-SZPZYZBQSA-N 0.000 claims 1
- CBNDBWHBUUWRCT-BJKOFHAPSA-N cyclopropyl-[5-[[4-[4-[[(3s,4r)-3-hydroxy-4-methoxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound C1[C@H](O)[C@H](OC)CN1CC1=CN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)N=C1C CBNDBWHBUUWRCT-BJKOFHAPSA-N 0.000 claims 1
- XTSXBUUVDQZQBR-XZOQPEGZSA-N cyclopropyl-[5-[[4-[4-[[(3s,4r)-3-hydroxy-4-methoxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]methanone Chemical compound C1[C@H](O)[C@H](OC)CN1CC1=CN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CNC4=CC=3)N=CC=2)N=C1C XTSXBUUVDQZQBR-XZOQPEGZSA-N 0.000 claims 1
- HNSGGOLPCJWHBE-GOTSBHOMSA-N cyclopropyl-[5-[[4-[4-[[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@@H](O)C1 HNSGGOLPCJWHBE-GOTSBHOMSA-N 0.000 claims 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 206010025135 lupus erythematosus Diseases 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 125000000168 pyrrolyl group Chemical group 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
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| PCT/US2013/022135 WO2013109882A1 (en) | 2012-01-20 | 2013-01-18 | Substituted pyrimidine compounds and their use as syk inhibitors |
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| SG11201602566XA (en) * | 2013-10-21 | 2016-05-30 | Genosco | Substituted pyrimidine compounds and their use as syk inhibitors |
| CN103969445B (zh) * | 2014-05-08 | 2015-09-30 | 中南大学 | 亚铁血红素—二氧化锰复合物的制备及其用于检测人IgG的方法 |
| EP3929190B1 (en) | 2014-10-13 | 2024-12-25 | Yuhan Corporation | Compounds and compositions for modulating egfr mutant kinase activities |
| CA2978823C (en) | 2014-12-29 | 2023-10-10 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Small molecule inhibitors of lactate dehydrogenase and methods of use thereof |
| WO2018228475A1 (zh) | 2017-06-14 | 2018-12-20 | 正大天晴药业集团股份有限公司 | Syk抑制剂及其使用方法 |
| DK3658547T3 (da) * | 2017-07-28 | 2023-10-16 | Yuhan Corp | Fremgangsmåde til fremstilling af n-(5-(4-(4-formyl-3-phenyl-1h-pyrazol-1-yl)pyrimidin-2-ylamino)-4-methoxy-2-morpholinophenyl)acrylamid |
| JP7109013B2 (ja) | 2019-03-19 | 2022-07-29 | ボロノイ インコーポレイテッド | ヘテロアリール誘導体、ヘテロアリール誘導体の生成方法、およびヘテロアリール誘導体を有効成分として含む医薬組成物 |
| US12157730B2 (en) | 2019-03-19 | 2024-12-03 | Voronoi Inc. | Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component |
| CA3129665A1 (en) | 2019-03-21 | 2020-09-24 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| KR20210152312A (ko) * | 2020-06-08 | 2021-12-15 | 주식회사 종근당 | 카나비노이드 수용체 (cb1 수용체) 길항제로서의 4-(4,5-디하이드로-1h-피라졸-1-닐)피리미딘 화합물 및 이를 포함하는 약제학적 조성물 |
| US20240285621A1 (en) * | 2020-09-23 | 2024-08-29 | Nerviano Medical Sciences S.R.L. | Pyrazolyl-pyrimidine derivatives as kinase inhibitors |
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| JP2000516231A (ja) * | 1996-08-09 | 2000-12-05 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 免疫調節物質としての４―置換β―カルボリン |
| JP2006524688A (ja) * | 2003-03-25 | 2006-11-02 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼのインヒビターとして有用なチアゾール |
| TW201016676A (en) * | 2008-10-03 | 2010-05-01 | Astrazeneca Ab | Heterocyclic derivatives and methods of use thereof |
| CA2780892C (en) * | 2009-11-13 | 2017-02-14 | Genosco | Kinase inhibitors |
| EP2668177B1 (en) * | 2011-01-28 | 2014-10-22 | Boehringer Ingelheim International GmbH | Substituted pyridinyl-pyrimidines and their use as medicaments |
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