DK2597955T3 - QUINOLINE DERIVATIVES AND MILK INHIBITORS CONTAINING THESE - Google Patents
QUINOLINE DERIVATIVES AND MILK INHIBITORS CONTAINING THESE Download PDFInfo
- Publication number
- DK2597955T3 DK2597955T3 DK11813209.1T DK11813209T DK2597955T3 DK 2597955 T3 DK2597955 T3 DK 2597955T3 DK 11813209 T DK11813209 T DK 11813209T DK 2597955 T3 DK2597955 T3 DK 2597955T3
- Authority
- DK
- Denmark
- Prior art keywords
- mmol
- bromo
- quinolin
- afford
- esi
- Prior art date
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- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title description 14
- 239000003112 inhibitor Substances 0.000 title description 3
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title 1
- 239000008267 milk Substances 0.000 title 1
- 210000004080 milk Anatomy 0.000 title 1
- 235000013336 milk Nutrition 0.000 title 1
- 239000000047 product Substances 0.000 description 501
- 239000007787 solid Substances 0.000 description 498
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 428
- 238000000034 method Methods 0.000 description 411
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 369
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 282
- 238000005160 1H NMR spectroscopy Methods 0.000 description 231
- 238000004128 high performance liquid chromatography Methods 0.000 description 231
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 222
- 239000000243 solution Substances 0.000 description 203
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 163
- -1 aminopropyl Chemical group 0.000 description 160
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 158
- 239000011541 reaction mixture Substances 0.000 description 135
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 124
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 113
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 112
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 103
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 94
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 87
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- 239000000203 mixture Substances 0.000 description 84
- IAVSUBSFIDLDNW-UHFFFAOYSA-N 2,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(Cl)=C(O)C(Cl)=C1 IAVSUBSFIDLDNW-UHFFFAOYSA-N 0.000 description 78
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 75
- AUELWJRRASQDKI-UHFFFAOYSA-N cyclohexyl carbamate Chemical compound NC(=O)OC1CCCCC1 AUELWJRRASQDKI-UHFFFAOYSA-N 0.000 description 67
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 62
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 61
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 61
- 239000000725 suspension Substances 0.000 description 59
- 125000001424 substituent group Chemical group 0.000 description 58
- 238000006243 chemical reaction Methods 0.000 description 57
- 239000000377 silicon dioxide Substances 0.000 description 57
- SKMHXQZCLNKWIE-UHFFFAOYSA-N (6-bromo-4-chloroquinolin-3-yl)-cyclopropylmethanone Chemical compound C1=NC2=CC=C(Br)C=C2C(Cl)=C1C(=O)C1CC1 SKMHXQZCLNKWIE-UHFFFAOYSA-N 0.000 description 56
- 239000012044 organic layer Substances 0.000 description 56
- 125000005466 alkylenyl group Chemical group 0.000 description 54
- CEBBVCKDURRDBD-UHFFFAOYSA-N 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(F)=C(O)C(Cl)=C1 CEBBVCKDURRDBD-UHFFFAOYSA-N 0.000 description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 53
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 50
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 46
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 45
- 239000000543 intermediate Substances 0.000 description 42
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 41
- 238000004440 column chromatography Methods 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
- XBEJPOZGAPQFPL-UHFFFAOYSA-N 2-chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound ClC1=C(O)C(OC)=CC(B2OC(C)(C)C(C)(C)O2)=C1 XBEJPOZGAPQFPL-UHFFFAOYSA-N 0.000 description 38
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 36
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- 239000002244 precipitate Substances 0.000 description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
- 125000001931 aliphatic group Chemical group 0.000 description 32
- 238000000746 purification Methods 0.000 description 31
- 150000001875 compounds Chemical class 0.000 description 30
- TZSUMDMNMCGUEP-UHFFFAOYSA-N 1-(6-bromo-4-chloroquinolin-3-yl)ethanone Chemical compound C1=CC(Br)=CC2=C(Cl)C(C(=O)C)=CN=C21 TZSUMDMNMCGUEP-UHFFFAOYSA-N 0.000 description 29
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 230000002829 reductive effect Effects 0.000 description 24
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 23
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 239000007789 gas Substances 0.000 description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000012043 crude product Substances 0.000 description 19
- 150000003839 salts Chemical class 0.000 description 19
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 238000006722 reduction reaction Methods 0.000 description 18
- BAZVFQBTJPBRTJ-UHFFFAOYSA-N 2-chloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1 BAZVFQBTJPBRTJ-UHFFFAOYSA-N 0.000 description 17
- 150000001412 amines Chemical class 0.000 description 17
- 229910052736 halogen Inorganic materials 0.000 description 17
- 150000002367 halogens Chemical class 0.000 description 17
- 125000000623 heterocyclic group Chemical group 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 16
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 238000002953 preparative HPLC Methods 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 125000003545 alkoxy group Chemical group 0.000 description 13
- 125000004103 aminoalkyl group Chemical group 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 13
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 12
- 101710154611 Maternal embryonic leucine zipper kinase Proteins 0.000 description 11
- 102100024299 Maternal embryonic leucine zipper kinase Human genes 0.000 description 11
- 125000003282 alkyl amino group Chemical group 0.000 description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 11
- 125000004093 cyano group Chemical group *C#N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 239000012458 free base Substances 0.000 description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 11
- WWQIKFZZILXJHG-UHFFFAOYSA-N (3-chloro-4-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(O)C(Cl)=C1 WWQIKFZZILXJHG-UHFFFAOYSA-N 0.000 description 10
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 10
- 229910021529 ammonia Inorganic materials 0.000 description 10
- 238000005342 ion exchange Methods 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 9
- 235000015320 potassium carbonate Nutrition 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 9
- 239000012264 purified product Substances 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- OLOLNAQGBLYQRK-UHFFFAOYSA-N 1-(6-bromo-4-chloroquinolin-3-yl)propan-1-one Chemical compound C1=CC(Br)=CC2=C(Cl)C(C(=O)CC)=CN=C21 OLOLNAQGBLYQRK-UHFFFAOYSA-N 0.000 description 8
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 8
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 8
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 7
- WFSJROCEOJANPD-UHFFFAOYSA-N 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound C1=C(O)C(OC)=CC(B2OC(C)(C)C(C)(C)O2)=C1 WFSJROCEOJANPD-UHFFFAOYSA-N 0.000 description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 7
- 206010006187 Breast cancer Diseases 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 6
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- 150000007945 N-acyl ureas Chemical class 0.000 description 6
- 125000005236 alkanoylamino group Chemical group 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 6
- LPTMGLRSJZIYAE-UHFFFAOYSA-N 1-(6-bromo-4-chloroquinolin-3-yl)-2-methylpropan-1-one Chemical compound C1=CC(Br)=CC2=C(Cl)C(C(=O)C(C)C)=CN=C21 LPTMGLRSJZIYAE-UHFFFAOYSA-N 0.000 description 5
- RGCFVPSBPNJZAU-UHFFFAOYSA-N 1-(6-bromo-4-chloroquinolin-3-yl)butan-1-one Chemical compound C1=CC(Br)=CC2=C(Cl)C(C(=O)CCC)=CN=C21 RGCFVPSBPNJZAU-UHFFFAOYSA-N 0.000 description 5
- KTQYJNVSVKKLGQ-UHFFFAOYSA-N 2,6-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(F)=C(O)C(F)=C1 KTQYJNVSVKKLGQ-UHFFFAOYSA-N 0.000 description 5
- OFCBNMYNAHUDGE-UHFFFAOYSA-N 2-chloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1 OFCBNMYNAHUDGE-UHFFFAOYSA-N 0.000 description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 5
- DKLRMTJDWREBQA-UHFFFAOYSA-N 6-bromo-4-chloro-3-methylsulfonylquinoline Chemical compound C1=CC(Br)=CC2=C(Cl)C(S(=O)(=O)C)=CN=C21 DKLRMTJDWREBQA-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 229930040373 Paraformaldehyde Natural products 0.000 description 5
- BMMUAHBETDHMFP-UHFFFAOYSA-N [6-bromo-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]quinolin-3-yl]-cyclopropylmethanone Chemical compound C1CN(C)CCN1C1CCN(C=2C3=CC(Br)=CC=C3N=CC=2C(=O)C2CC2)CC1 BMMUAHBETDHMFP-UHFFFAOYSA-N 0.000 description 5
- LYERWNWLCXUXLV-UHFFFAOYSA-N [6-bromo-4-[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]quinolin-3-yl]-cyclopropylmethanone Chemical compound C1CC(CN2CCCC2)CCN1C=1C2=CC(Br)=CC=C2N=CC=1C(=O)C1CC1 LYERWNWLCXUXLV-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-GUEYOVJQSA-N acetic acid-d4 Chemical compound [2H]OC(=O)C([2H])([2H])[2H] QTBSBXVTEAMEQO-GUEYOVJQSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 5
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 5
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 229920002866 paraformaldehyde Polymers 0.000 description 5
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- NDYMQOUYJJXCKJ-UHFFFAOYSA-N (4-fluorophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CCOCC1 NDYMQOUYJJXCKJ-UHFFFAOYSA-N 0.000 description 4
- PHJOQCVXKGKDRW-UHFFFAOYSA-N 1-[6-bromo-4-[4-[(dimethylamino)methyl]anilino]quinolin-3-yl]ethanone Chemical compound C1=CC(CN(C)C)=CC=C1NC1=C(C(C)=O)C=NC2=CC=C(Br)C=C12 PHJOQCVXKGKDRW-UHFFFAOYSA-N 0.000 description 4
- NNCCQALFJIMRKB-UHFFFAOYSA-N 4-[(dimethylamino)methyl]aniline Chemical compound CN(C)CC1=CC=C(N)C=C1 NNCCQALFJIMRKB-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 208000030761 polycystic kidney disease Diseases 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- AVYZECDGRVLACB-UHFFFAOYSA-N pyridin-2-yl N-piperidin-3-ylcarbamate Chemical compound N1=C(C=CC=C1)OC(NC1CNCCC1)=O AVYZECDGRVLACB-UHFFFAOYSA-N 0.000 description 1
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
- MIROPXUFDXCYLG-UHFFFAOYSA-N pyridine-2,5-diamine Chemical compound NC1=CC=C(N)N=C1 MIROPXUFDXCYLG-UHFFFAOYSA-N 0.000 description 1
- IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000024642 stem cell division Effects 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- AKQXKEBCONUWCL-UHFFFAOYSA-N tert-butyl 3-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N)C1 AKQXKEBCONUWCL-UHFFFAOYSA-N 0.000 description 1
- CMIBWIAICVBURI-UHFFFAOYSA-N tert-butyl 3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)C1 CMIBWIAICVBURI-UHFFFAOYSA-N 0.000 description 1
- RMHRRMBFHGEDSR-UHFFFAOYSA-N tert-butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=N1 RMHRRMBFHGEDSR-UHFFFAOYSA-N 0.000 description 1
- UOFXCDLVMBOPFE-UHFFFAOYSA-N tert-butyl 4-(5-aminopyrimidin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(N)C=N1 UOFXCDLVMBOPFE-UHFFFAOYSA-N 0.000 description 1
- CUIDOEHSIWDYJI-UHFFFAOYSA-N tert-butyl 4-[5-[(3-acetyl-6-bromoquinolin-4-yl)amino]pyridin-2-yl]piperazine-1-carboxylate Chemical compound CC(=O)C1=CN=C2C=CC(Br)=CC2=C1NC(C=N1)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 CUIDOEHSIWDYJI-UHFFFAOYSA-N 0.000 description 1
- AXMULTJEVLRTGI-UHFFFAOYSA-N tert-butyl 4-[5-[(3-acetyl-6-bromoquinolin-4-yl)amino]pyrimidin-2-yl]piperazine-1-carboxylate Chemical compound CC(=O)C1=CN=C2C=CC(Br)=CC2=C1NC(C=N1)=CN=C1N1CCN(C(=O)OC(C)(C)C)CC1 AXMULTJEVLRTGI-UHFFFAOYSA-N 0.000 description 1
- JCSWPWOSWNXOCJ-UHFFFAOYSA-N tert-butyl 4-[5-[[3-acetyl-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-4-yl]amino]pyridin-2-yl]piperazine-1-carboxylate Chemical compound CC(=O)C1=CN=C2C=CC(C=3C=C(Cl)C(O)=C(Cl)C=3)=CC2=C1NC(C=N1)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 JCSWPWOSWNXOCJ-UHFFFAOYSA-N 0.000 description 1
- SWKROQOSIRFTBH-UHFFFAOYSA-N tert-butyl 4-[5-[[3-acetyl-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-4-yl]amino]pyrimidin-2-yl]piperazine-1-carboxylate Chemical compound CC(=O)C1=CN=C2C=CC(C=3C=C(Cl)C(O)=C(F)C=3)=CC2=C1NC(C=N1)=CN=C1N1CCN(C(=O)OC(C)(C)C)CC1 SWKROQOSIRFTBH-UHFFFAOYSA-N 0.000 description 1
- AMEWSQWCYGIREA-UHFFFAOYSA-N tert-butyl 4-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyridin-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 AMEWSQWCYGIREA-UHFFFAOYSA-N 0.000 description 1
- GPTXCAZYUMDUMN-UHFFFAOYSA-N tert-butyl n-(2-hydroxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCO GPTXCAZYUMDUMN-UHFFFAOYSA-N 0.000 description 1
- FEYLUKDSKVSMSZ-UHFFFAOYSA-N tert-butyl n-(4-aminocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(N)CC1 FEYLUKDSKVSMSZ-UHFFFAOYSA-N 0.000 description 1
- WQBYRXFGNMDMDB-UHFFFAOYSA-N tert-butyl n-[1-[5-[(3-acetyl-6-bromoquinolin-4-yl)amino]pyridin-2-yl]pyrrolidin-3-yl]-n-methylcarbamate Chemical compound C1C(N(C)C(=O)OC(C)(C)C)CCN1C(N=C1)=CC=C1NC1=C(C(C)=O)C=NC2=CC=C(Br)C=C12 WQBYRXFGNMDMDB-UHFFFAOYSA-N 0.000 description 1
- NSTGWEBFFVHFJD-UHFFFAOYSA-N tert-butyl n-[1-[5-[(3-acetyl-6-bromoquinolin-4-yl)amino]pyridin-2-yl]pyrrolidin-3-yl]carbamate Chemical compound CC(=O)C1=CN=C2C=CC(Br)=CC2=C1NC(C=N1)=CC=C1N1CCC(NC(=O)OC(C)(C)C)C1 NSTGWEBFFVHFJD-UHFFFAOYSA-N 0.000 description 1
- MNKMDCPJBUUFRC-UHFFFAOYSA-N tert-butyl n-[1-[5-[(6-bromo-3-propanoylquinolin-4-yl)amino]pyridin-2-yl]piperidin-3-yl]carbamate Chemical compound CCC(=O)C1=CN=C2C=CC(Br)=CC2=C1NC(C=N1)=CC=C1N1CCCC(NC(=O)OC(C)(C)C)C1 MNKMDCPJBUUFRC-UHFFFAOYSA-N 0.000 description 1
- KVLCRXMJDKQZQU-UHFFFAOYSA-N tert-butyl n-[1-[5-[(6-bromo-3-propanoylquinolin-4-yl)amino]pyridin-2-yl]pyrrolidin-3-yl]carbamate Chemical compound CCC(=O)C1=CN=C2C=CC(Br)=CC2=C1NC(C=N1)=CC=C1N1CCC(NC(=O)OC(C)(C)C)C1 KVLCRXMJDKQZQU-UHFFFAOYSA-N 0.000 description 1
- IKEQNPGLEVVBJE-UHFFFAOYSA-N tert-butyl n-[1-[5-[[6-(3-chloro-5-fluoro-4-hydroxyphenyl)-3-propanoylquinolin-4-yl]amino]pyridin-2-yl]piperidin-3-yl]carbamate Chemical compound CCC(=O)C1=CN=C2C=CC(C=3C=C(Cl)C(O)=C(F)C=3)=CC2=C1NC(C=N1)=CC=C1N1CCCC(NC(=O)OC(C)(C)C)C1 IKEQNPGLEVVBJE-UHFFFAOYSA-N 0.000 description 1
- XHIMNUDJTUOAIU-UHFFFAOYSA-N tert-butyl n-[1-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 XHIMNUDJTUOAIU-UHFFFAOYSA-N 0.000 description 1
- VRHQIMMGKZZFIK-UHFFFAOYSA-N tert-butyl n-[1-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyrimidin-2-yl]piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C(N=C1)=NC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 VRHQIMMGKZZFIK-UHFFFAOYSA-N 0.000 description 1
- YKGOJBCBAUQJFY-UHFFFAOYSA-N tert-butyl n-[2-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyridin-2-yl]oxyethyl]carbamate Chemical compound C1=NC(OCCNC(=O)OC(C)(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 YKGOJBCBAUQJFY-UHFFFAOYSA-N 0.000 description 1
- KJFFKWZRBGVSOJ-UHFFFAOYSA-N tert-butyl n-[4-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]-1-adamantyl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)(CC2C3)CC3CC1C2NC(C1=CC(Br)=CC=C1N=C1)=C1C(=O)C1CC1 KJFFKWZRBGVSOJ-UHFFFAOYSA-N 0.000 description 1
- DIVXUHKRFRDNQR-UHFFFAOYSA-N tert-butyl n-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 DIVXUHKRFRDNQR-UHFFFAOYSA-N 0.000 description 1
- KDLVVPMTCYKKCH-UHFFFAOYSA-N tert-butyl n-[[4-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]phenyl]methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 KDLVVPMTCYKKCH-UHFFFAOYSA-N 0.000 description 1
- SKIATQYFADHZNJ-UHFFFAOYSA-N tert-butyl n-methyl-n-[1-(5-nitropyridin-2-yl)pyrrolidin-3-yl]carbamate Chemical compound C1C(N(C)C(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=N1 SKIATQYFADHZNJ-UHFFFAOYSA-N 0.000 description 1
- RTXNDTNDOHQMTI-UHFFFAOYSA-N tert-butyl n-methyl-n-piperidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C1CCCNC1 RTXNDTNDOHQMTI-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36951910P | 2010-07-30 | 2010-07-30 | |
| PCT/US2011/045792 WO2012016082A1 (en) | 2010-07-30 | 2011-07-28 | Quinoline derivatives and melk inhibitors containing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2597955T3 true DK2597955T3 (en) | 2016-03-14 |
Family
ID=45530500
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK11813209.1T DK2597955T3 (en) | 2010-07-30 | 2011-07-28 | QUINOLINE DERIVATIVES AND MILK INHIBITORS CONTAINING THESE |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US9120749B2 (enExample) |
| EP (1) | EP2597955B1 (enExample) |
| JP (1) | JP5849303B2 (enExample) |
| KR (1) | KR101826382B1 (enExample) |
| CN (1) | CN103153063B (enExample) |
| AU (1) | AU2011282588B2 (enExample) |
| BR (1) | BR112013002182B8 (enExample) |
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