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
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- 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
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- 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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| NZ718576A (en) * | 2013-10-21 | 2019-11-29 | 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 |
| NZ730012A (en) | 2014-10-13 | 2019-06-28 | Yuhan Corp | Compounds and compositions for modulating egfr mutant kinase activities |
| PL3240785T3 (pl) | 2014-12-29 | 2021-12-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Inhibitory drobnocząsteczkowe dehydrogenazy mleczanowej i sposoby ich wykorzystania |
| CA3065114A1 (en) * | 2017-06-14 | 2018-12-20 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Syk inhibitor and use method therefor |
| JP7189932B2 (ja) * | 2017-07-28 | 2022-12-14 | ユハン コーポレーション | タンパク質キナーゼに対する選択的阻害剤の合成に有用な中間体及びそれを調製するためのプロセス |
| AU2020240382B2 (en) | 2019-03-19 | 2022-08-25 | Voronoi Inc. | Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component |
| US12157730B2 (en) | 2019-03-19 | 2024-12-03 | Voronoi Inc. | Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component |
| EP3942045A1 (en) | 2019-03-21 | 2022-01-26 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| EP4054579A1 (en) | 2019-11-08 | 2022-09-14 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
| 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 |
| CN116323595B (zh) * | 2020-09-23 | 2025-08-19 | 内尔维亚诺医疗科学公司 | 作为激酶抑制剂的吡唑基-嘧啶衍生物 |
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| WO2004087698A2 (en) * | 2003-03-25 | 2004-10-14 | Vertex Pharmaceuticals Incorporated | Thiazoles useful as inhibitors of protein kinases |
| TW201016676A (en) | 2008-10-03 | 2010-05-01 | Astrazeneca Ab | Heterocyclic derivatives and methods of use thereof |
| US8629132B2 (en) * | 2009-11-13 | 2014-01-14 | Genosco | Kinase inhibitors |
| JP5959537B2 (ja) * | 2011-01-28 | 2016-08-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 置換ピリジニル−ピリミジン及び医薬としてのその使用 |
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