HRP20000209A2 - Bicyclic kinase inhibitors - Google Patents
Bicyclic kinase inhibitors Download PDFInfo
- Publication number
- HRP20000209A2 HRP20000209A2 HR20000209A HRP20000209A HRP20000209A2 HR P20000209 A2 HRP20000209 A2 HR P20000209A2 HR 20000209 A HR20000209 A HR 20000209A HR P20000209 A HRP20000209 A HR P20000209A HR P20000209 A2 HRP20000209 A2 HR P20000209A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- hydrogen
- amino
- heteroalkyl
- formula
- Prior art date
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- 125000002619 bicyclic group Chemical group 0.000 title 1
- 229940043355 kinase inhibitor Drugs 0.000 title 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 219
- 238000000034 method Methods 0.000 claims abstract description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 466
- 239000001257 hydrogen Substances 0.000 claims description 404
- 229910052739 hydrogen Inorganic materials 0.000 claims description 404
- -1 nitro, cyano, amino, monosubstituted amino Chemical group 0.000 claims description 340
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 260
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 165
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 117
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 100
- 125000001424 substituent group Chemical group 0.000 claims description 82
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 77
- 125000000623 heterocyclic group Chemical group 0.000 claims description 71
- 229910052736 halogen Inorganic materials 0.000 claims description 67
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 66
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 66
- 150000002367 halogens Chemical group 0.000 claims description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
- 125000003545 alkoxy group Chemical group 0.000 claims description 55
- 229910052757 nitrogen Inorganic materials 0.000 claims description 53
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 52
- 125000003118 aryl group Chemical group 0.000 claims description 52
- 238000006243 chemical reaction Methods 0.000 claims description 46
- 239000000460 chlorine Chemical group 0.000 claims description 42
- 229910052801 chlorine Chemical group 0.000 claims description 42
- 125000001072 heteroaryl group Chemical group 0.000 claims description 41
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 39
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 39
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 36
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 35
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 34
- 125000001188 haloalkyl group Chemical group 0.000 claims description 34
- 125000003282 alkyl amino group Chemical group 0.000 claims description 32
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 30
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 26
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 26
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 22
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 22
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 22
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 22
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 19
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 18
- 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 17
- 125000002252 acyl group Chemical group 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 239000011737 fluorine Substances 0.000 claims description 14
- 238000009472 formulation Methods 0.000 claims description 14
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical group COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 12
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 239000000651 prodrug Substances 0.000 claims description 9
- 229940002612 prodrug Drugs 0.000 claims description 9
- 125000004442 acylamino group Chemical group 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- ZSMYZLKEZDYVPI-UHFFFAOYSA-N 3-(4-fluorophenyl)-1-hydroxy-2-(pyridin-4-yl)-1h-pyrrolo[3,2-b]pyridine Chemical compound C12=NC=CC=C2N(O)C(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 ZSMYZLKEZDYVPI-UHFFFAOYSA-N 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 6
- LXTFKKVJJMDQNR-UHFFFAOYSA-N 7-(4-fluorophenyl)-6-pyridin-4-yl-5h-pyrrolo[2,3-b]pyrazine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC2=NC=CN=C12 LXTFKKVJJMDQNR-UHFFFAOYSA-N 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 claims description 4
- FWXGTZHINXLKJS-UHFFFAOYSA-N 4-[2-[3-(4-fluorophenyl)-2-pyridin-4-ylpyrrolo[3,2-b]pyridin-1-yl]oxyethyl]morpholine Chemical compound C1=CC(F)=CC=C1C(C1=NC=CC=C1N1OCCN2CCOCC2)=C1C1=CC=NC=C1 FWXGTZHINXLKJS-UHFFFAOYSA-N 0.000 claims description 4
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 4
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- IDYORHLXHWWCGG-UHFFFAOYSA-N 2-[[4-[3-(4-fluorophenyl)-1h-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]amino]ethanol Chemical compound C1=NC(NCCO)=CC(C2=C(C3=NC=CC=C3N2)C=2C=CC(F)=CC=2)=C1 IDYORHLXHWWCGG-UHFFFAOYSA-N 0.000 claims description 3
- SVHIOPOOPNXCLH-UHFFFAOYSA-N 3-(4-fluorophenyl)-1-methyl-2-pyridin-4-ylpyrrolo[3,2-b]pyridine Chemical compound C12=NC=CC=C2N(C)C(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 SVHIOPOOPNXCLH-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 3
- KRIMJAWAOZBDQB-UHFFFAOYSA-N n-[4-[7-(4-fluorophenyl)-5h-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)C)=CC(C2=C(C3=NC=CN=C3N2)C=2C=CC(F)=CC=2)=C1 KRIMJAWAOZBDQB-UHFFFAOYSA-N 0.000 claims description 3
- DPGNJQAIOXNWEY-UHFFFAOYSA-N 3-(4-fluorophenyl)-2-pyridin-4-yl-1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC2=CC=CN=C12 DPGNJQAIOXNWEY-UHFFFAOYSA-N 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 27
- 238000011321 prophylaxis Methods 0.000 claims 3
- POSGPOILCJXRFO-UHFFFAOYSA-N 4-[2-[3-(4-fluorophenyl)-2-pyridin-4-ylpyrrolo[3,2-b]pyridin-1-yl]ethyl]morpholine Chemical compound C1=CC(F)=CC=C1C(C1=NC=CC=C1N1CCN2CCOCC2)=C1C1=CC=NC=C1 POSGPOILCJXRFO-UHFFFAOYSA-N 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 11
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 abstract description 9
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 abstract description 9
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 144
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 71
- 239000011541 reaction mixture Substances 0.000 description 70
- 239000000243 solution Substances 0.000 description 61
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 55
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 46
- 239000007787 solid Substances 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- 201000010099 disease Diseases 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 102100040247 Tumor necrosis factor Human genes 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 16
- 239000002585 base Substances 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 15
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
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- 239000002253 acid Substances 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 150000003254 radicals Chemical class 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- 239000004215 Carbon black (E152) Substances 0.000 description 10
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
- 125000005843 halogen group Chemical group 0.000 description 10
- 229930195733 hydrocarbon Natural products 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
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- 125000004183 alkoxy alkyl group Chemical group 0.000 description 7
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 7
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
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- 108010002352 Interleukin-1 Proteins 0.000 description 5
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- NNYREQBXDUEBDD-UHFFFAOYSA-N ethyl 3-hydroxypyridine-2-carboxylate Chemical compound CCOC(=O)C1=NC=CC=C1O NNYREQBXDUEBDD-UHFFFAOYSA-N 0.000 description 5
- 229960004979 fampridine Drugs 0.000 description 5
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- 125000003884 phenylalkyl group Chemical group 0.000 description 5
- 125000006413 ring segment Chemical group 0.000 description 5
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- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
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- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
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- UGMGEABSYVPOQM-UHFFFAOYSA-N tert-butyl 3-(4-fluorophenyl)-2-pyridin-4-ylpyrrolo[3,2-b]pyridine-1-carboxylate Chemical compound C12=NC=CC=C2N(C(=O)OC(C)(C)C)C(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 UGMGEABSYVPOQM-UHFFFAOYSA-N 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000001149 thermolysis Methods 0.000 description 1
- YJSKZIATOGOJEB-UHFFFAOYSA-N thieno[2,3-b]pyrazine Chemical compound C1=CN=C2SC=CC2=N1 YJSKZIATOGOJEB-UHFFFAOYSA-N 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- MKYRMMMSZSVIGD-UHFFFAOYSA-N thieno[3,2-c]pyridine Chemical compound N1=CC=C2SC=CC2=C1 MKYRMMMSZSVIGD-UHFFFAOYSA-N 0.000 description 1
- GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
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- JSQJUDVTRRCSRU-UHFFFAOYSA-N tributyl(chloro)silane Chemical compound CCCC[Si](Cl)(CCCC)CCCC JSQJUDVTRRCSRU-UHFFFAOYSA-N 0.000 description 1
- MEBRQLCKPRKBOH-UHFFFAOYSA-K trichloro(ethyl)stannane Chemical compound CC[Sn](Cl)(Cl)Cl MEBRQLCKPRKBOH-UHFFFAOYSA-K 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
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- 238000003828 vacuum filtration Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
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- 229910052725 zinc Inorganic materials 0.000 description 1
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Classifications
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/70—Sulfur atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/20—Nitrogen atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
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- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/18—Oxygen or sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
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- C07D487/04—Ortho-condensed systems
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
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US6254897P | 1997-10-20 | 1997-10-20 | |
US7551598P | 1998-02-20 | 1998-02-20 | |
US9691698P | 1998-08-18 | 1998-08-18 | |
PCT/EP1998/006472 WO1999020624A1 (en) | 1997-10-20 | 1998-10-13 | Bicyclic kinase inhibitors |
Publications (1)
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HRP20000209A2 true HRP20000209A2 (en) | 2001-04-30 |
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Application Number | Title | Priority Date | Filing Date |
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HR20000209A HRP20000209A2 (en) | 1997-10-20 | 2000-04-12 | Bicyclic kinase inhibitors |
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US (4) | US6316464B1 (xx) |
EP (1) | EP1025102B1 (xx) |
JP (1) | JP3579350B2 (xx) |
KR (1) | KR100378937B1 (xx) |
CN (1) | CN1279682A (xx) |
AT (1) | ATE267200T1 (xx) |
AU (1) | AU745579B2 (xx) |
BR (1) | BR9812944A (xx) |
CA (1) | CA2306870A1 (xx) |
CO (1) | CO4980857A1 (xx) |
DE (1) | DE69824029T2 (xx) |
ES (1) | ES2221213T3 (xx) |
HR (1) | HRP20000209A2 (xx) |
HU (1) | HUP0100348A3 (xx) |
ID (1) | ID27124A (xx) |
IL (1) | IL135302A0 (xx) |
MA (1) | MA26555A1 (xx) |
NO (1) | NO316734B1 (xx) |
NZ (1) | NZ503685A (xx) |
PE (1) | PE120999A1 (xx) |
PL (1) | PL340412A1 (xx) |
RU (1) | RU2219178C2 (xx) |
TR (1) | TR200001079T2 (xx) |
TW (1) | TWI224596B (xx) |
WO (1) | WO1999020624A1 (xx) |
YU (1) | YU22000A (xx) |
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-
1998
- 1998-10-13 CN CN98811246A patent/CN1279682A/zh active Pending
- 1998-10-13 DE DE69824029T patent/DE69824029T2/de not_active Expired - Fee Related
- 1998-10-13 NZ NZ503685A patent/NZ503685A/en unknown
- 1998-10-13 ES ES98951516T patent/ES2221213T3/es not_active Expired - Lifetime
- 1998-10-13 WO PCT/EP1998/006472 patent/WO1999020624A1/en active IP Right Grant
- 1998-10-13 HU HU0100348A patent/HUP0100348A3/hu unknown
- 1998-10-13 CA CA002306870A patent/CA2306870A1/en not_active Abandoned
- 1998-10-13 ID IDW20000729A patent/ID27124A/id unknown
- 1998-10-13 PL PL98340412A patent/PL340412A1/xx unknown
- 1998-10-13 JP JP2000516966A patent/JP3579350B2/ja not_active Expired - Fee Related
- 1998-10-13 AT AT98951516T patent/ATE267200T1/de not_active IP Right Cessation
- 1998-10-13 EP EP98951516A patent/EP1025102B1/en not_active Expired - Lifetime
- 1998-10-13 TR TR2000/01079T patent/TR200001079T2/xx unknown
- 1998-10-13 YU YU22000A patent/YU22000A/sh unknown
- 1998-10-13 IL IL13530298A patent/IL135302A0/xx unknown
- 1998-10-13 RU RU2000110738/04A patent/RU2219178C2/ru not_active IP Right Cessation
- 1998-10-13 KR KR10-2000-7004272A patent/KR100378937B1/ko not_active IP Right Cessation
- 1998-10-13 BR BR9812944-9A patent/BR9812944A/pt not_active IP Right Cessation
- 1998-10-13 AU AU97499/98A patent/AU745579B2/en not_active Ceased
- 1998-10-16 CO CO98060325A patent/CO4980857A1/es unknown
- 1998-10-16 US US09/174,299 patent/US6316464B1/en not_active Expired - Fee Related
- 1998-10-16 PE PE1998000976A patent/PE120999A1/es not_active Application Discontinuation
- 1998-10-16 MA MA25301A patent/MA26555A1/fr unknown
- 1998-10-19 TW TW087117244A patent/TWI224596B/zh not_active IP Right Cessation
-
2000
- 2000-04-12 HR HR20000209A patent/HRP20000209A2/hr not_active Application Discontinuation
- 2000-04-13 NO NO20001940A patent/NO316734B1/no not_active IP Right Cessation
-
2001
- 2001-04-19 US US09/839,710 patent/US6630485B2/en not_active Expired - Fee Related
- 2001-04-19 US US09/839,712 patent/US6479507B2/en not_active Expired - Fee Related
-
2002
- 2002-09-17 US US10/245,906 patent/US20030139462A1/en not_active Abandoned
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