JP5386508B2 - インドリル−ピリドン誘導体類 - Google Patents
インドリル−ピリドン誘導体類 Download PDFInfo
- Publication number
- JP5386508B2 JP5386508B2 JP2010543556A JP2010543556A JP5386508B2 JP 5386508 B2 JP5386508 B2 JP 5386508B2 JP 2010543556 A JP2010543556 A JP 2010543556A JP 2010543556 A JP2010543556 A JP 2010543556A JP 5386508 B2 JP5386508 B2 JP 5386508B2
- Authority
- JP
- Japan
- Prior art keywords
- title compound
- carboxylic acid
- oxo
- dihydro
- pyrazole
- 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.)
- Expired - Fee Related
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- NRGVEGWSRITVOR-UHFFFAOYSA-N 3-(1h-indol-2-yl)-1h-pyridin-2-one Chemical class OC1=NC=CC=C1C1=CC2=CC=CC=C2N1 NRGVEGWSRITVOR-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 520
- -1 hydroxy, methyl Chemical group 0.000 claims description 114
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 150000002431 hydrogen Chemical class 0.000 claims description 25
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 22
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 201000011510 cancer Diseases 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 239000011593 sulfur Chemical group 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- KGDOHXYALMXHLF-UHFFFAOYSA-N 1-benzylpyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC=C1 KGDOHXYALMXHLF-UHFFFAOYSA-N 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 238000001959 radiotherapy Methods 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- YRNZHBVRTDDGNB-UHFFFAOYSA-N 1-benzyl-n-[5-(1h-indol-2-yl)-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C=1NC(=O)C(C=2NC3=CC=CC=C3C=2)=CC=1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 YRNZHBVRTDDGNB-UHFFFAOYSA-N 0.000 claims description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 238000002512 chemotherapy Methods 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 229940127089 cytotoxic agent Drugs 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- GEBXRQMORXJPGN-UHFFFAOYSA-N 1-[(4-methylphenyl)methyl]-n-[6-oxo-5-[5-(piperidin-1-ylmethyl)-1h-indol-2-yl]-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1CN1N=CC(C(=O)NC=2C=C(C(=O)NC=2)C=2NC3=CC=C(CN4CCCCC4)C=C3C=2)=C1 GEBXRQMORXJPGN-UHFFFAOYSA-N 0.000 claims description 2
- DISCGKGWZKLOSH-UHFFFAOYSA-N 1-benzyl-n-[5-[5-(2,2-dimethyl-3-piperidin-1-ylpropoxy)-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1CCCCN1CC(C)(C)COC(C=C1C=2)=CC=C1NC=2C(C(NC=1)=O)=CC=1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 DISCGKGWZKLOSH-UHFFFAOYSA-N 0.000 claims description 2
- ZSYVTFSMHIZBJT-UHFFFAOYSA-N 1-benzyl-n-[5-[5-(2,2-dimethyl-3-pyrrolidin-1-ylpropoxy)-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1CCCN1CC(C)(C)COC(C=C1C=2)=CC=C1NC=2C(C(NC=1)=O)=CC=1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 ZSYVTFSMHIZBJT-UHFFFAOYSA-N 0.000 claims description 2
- DKDWHPAIWPQMDV-UHFFFAOYSA-N 1-benzyl-n-[5-[5-[(4-fluoropiperidin-1-yl)methyl]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1CC(F)CCN1CC1=CC=C(NC(=C2)C=3C(NC=C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)C=3)=O)C2=C1 DKDWHPAIWPQMDV-UHFFFAOYSA-N 0.000 claims description 2
- QENZBLJVRSQXHR-UHFFFAOYSA-N 1-benzyl-n-[5-[5-[(4-methylpiperidin-1-yl)methyl]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1CC(C)CCN1CC1=CC=C(NC(=C2)C=3C(NC=C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)C=3)=O)C2=C1 QENZBLJVRSQXHR-UHFFFAOYSA-N 0.000 claims description 2
- OUZSVHBSAIWGAB-UHFFFAOYSA-N 1-benzyl-n-[5-[5-[1-(dimethylamino)-2-methylpropan-2-yl]oxy-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C=1C2=CC(OC(C)(C)CN(C)C)=CC=C2NC=1C(C(NC=1)=O)=CC=1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 OUZSVHBSAIWGAB-UHFFFAOYSA-N 0.000 claims description 2
- WMBKHLMCZPQUSY-UHFFFAOYSA-N 1-benzyl-n-[5-[5-[3-(diethylamino)-2,2-dimethylpropoxy]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C=1C2=CC(OCC(C)(C)CN(CC)CC)=CC=C2NC=1C(C(NC=1)=O)=CC=1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 WMBKHLMCZPQUSY-UHFFFAOYSA-N 0.000 claims description 2
- REQMZUHAMVOEON-UHFFFAOYSA-N 1-benzyl-n-[5-[5-[3-(dimethylamino)-2,2-dimethylpropoxy]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C=1C2=CC(OCC(C)(C)CN(C)C)=CC=C2NC=1C(C(NC=1)=O)=CC=1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 REQMZUHAMVOEON-UHFFFAOYSA-N 0.000 claims description 2
- PZNCUDMYMQBNPI-OAQYLSRUSA-N 1-benzyl-n-[5-[5-[[(2r)-2-methylpiperidin-1-yl]methyl]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C[C@@H]1CCCCN1CC1=CC=C(NC(=C2)C=3C(NC=C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)C=3)=O)C2=C1 PZNCUDMYMQBNPI-OAQYLSRUSA-N 0.000 claims description 2
- ITWISLBDFHAZFK-OYRHEFFESA-N 1-benzyl-n-[5-[5-[[(2r,6s)-2,6-dimethylmorpholin-4-yl]methyl]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1CC1=CC=C(NC(=C2)C=3C(NC=C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)C=3)=O)C2=C1 ITWISLBDFHAZFK-OYRHEFFESA-N 0.000 claims description 2
- KIBWTTYZBWVWLR-SZPZYZBQSA-N 1-benzyl-n-[5-[5-[[(2r,6s)-2,6-dimethylpiperidin-1-yl]methyl]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C[C@H]1CCC[C@@H](C)N1CC1=CC=C(NC(=C2)C=3C(NC=C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)C=3)=O)C2=C1 KIBWTTYZBWVWLR-SZPZYZBQSA-N 0.000 claims description 2
- PZNCUDMYMQBNPI-NRFANRHFSA-N 1-benzyl-n-[5-[5-[[(2s)-2-methylpiperidin-1-yl]methyl]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C[C@H]1CCCCN1CC1=CC=C(NC(=C2)C=3C(NC=C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)C=3)=O)C2=C1 PZNCUDMYMQBNPI-NRFANRHFSA-N 0.000 claims description 2
- NOMVGDXJBPVSOA-UHFFFAOYSA-N 1-benzyl-n-[5-[5-[[[3-(dimethylamino)-2,2-dimethylpropyl]-ethylamino]methyl]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C=1C2=CC(CN(CC)CC(C)(C)CN(C)C)=CC=C2NC=1C(C(NC=1)=O)=CC=1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 NOMVGDXJBPVSOA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 206010052779 Transplant rejections Diseases 0.000 claims description 2
- 239000000824 cytostatic agent Substances 0.000 claims description 2
- 239000002254 cytotoxic agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- APAITVFDOPBSBV-UHFFFAOYSA-N n-[5-[5-[(4-fluoropiperidin-1-yl)methyl]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]-1-(1-phenylethyl)pyrazole-4-carboxamide Chemical compound C1=C(C(=O)NC=2C=C(C(=O)NC=2)C=2NC3=CC=C(CN4CCC(F)CC4)C=C3C=2)C=NN1C(C)C1=CC=CC=C1 APAITVFDOPBSBV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 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 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 102000001253 Protein Kinase Human genes 0.000 claims 5
- 108060006633 protein kinase Proteins 0.000 claims 5
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 claims 2
- 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 claims 2
- 208000024891 symptom Diseases 0.000 claims 2
- OEKPFDMUKNSTBS-UHFFFAOYSA-N 1-benzyl-n-[6-oxo-5-[5-(piperidin-1-ylmethyl)-1h-indol-2-yl]-1h-pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C=1)=CNC(=O)C=1C(NC1=CC=2)=CC1=CC=2CN1CCCCC1 OEKPFDMUKNSTBS-UHFFFAOYSA-N 0.000 claims 1
- 230000005856 abnormality Effects 0.000 claims 1
- 230000001363 autoimmune Effects 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- WZFHXTBJQNYCNB-BHIFYINESA-N n-[5-[5-[[(2r,6s)-2,6-dimethylmorpholin-4-yl]methyl]-1h-indol-2-yl]-6-oxo-1h-pyridin-3-yl]-1-[(1r)-1-phenylethyl]pyrazole-4-carboxamide Chemical compound C1([C@@H](C)N2N=CC(=C2)C(=O)NC=2C=C(C(=O)NC=2)C=2NC3=CC=C(CN4C[C@@H](C)O[C@@H](C)C4)C=C3C=2)=CC=CC=C1 WZFHXTBJQNYCNB-BHIFYINESA-N 0.000 claims 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 543
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 369
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 255
- 239000007787 solid Substances 0.000 description 215
- 238000005481 NMR spectroscopy Methods 0.000 description 191
- 238000002474 experimental method Methods 0.000 description 188
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 186
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 141
- 238000001665 trituration Methods 0.000 description 139
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 130
- 238000000746 purification Methods 0.000 description 89
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 77
- 238000002360 preparation method Methods 0.000 description 74
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- 239000012043 crude product Substances 0.000 description 60
- 238000003818 flash chromatography Methods 0.000 description 58
- 239000011541 reaction mixture Substances 0.000 description 57
- 239000000243 solution Substances 0.000 description 56
- 229910004298 SiO 2 Inorganic materials 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 41
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 239000011734 sodium Substances 0.000 description 28
- 108010019244 Checkpoint Kinase 1 Proteins 0.000 description 27
- 102000006459 Checkpoint Kinase 1 Human genes 0.000 description 27
- 239000010410 layer Substances 0.000 description 27
- 238000002953 preparative HPLC Methods 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
- 239000012267 brine Substances 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- 239000003921 oil Substances 0.000 description 20
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- 229960005277 gemcitabine Drugs 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 17
- 238000010626 work up procedure Methods 0.000 description 17
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000001816 cooling Methods 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- AGBUHNSJFSPPNR-UHFFFAOYSA-N tert-butyl 5-(2-tert-butylsilyloxypropan-2-yl)indole-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1C=CC2=CC(=CC=C12)C(O[SiH2]C(C)(C)C)(C)C AGBUHNSJFSPPNR-UHFFFAOYSA-N 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- 239000006260 foam Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- 238000001914 filtration Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
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Images
Classifications
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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| GBGB0818695.9A GB0818695D0 (en) | 2008-10-11 | 2008-10-11 | New chemical compounds |
| GB0818695.9 | 2008-10-11 | ||
| PCT/GB2009/000149 WO2009093012A1 (en) | 2008-01-22 | 2009-01-20 | Indolyl- pyridone derivatives having checkpoint kinase 1 inhibitory activity |
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| JP5386508B2 (ja) | 2008-01-22 | 2014-01-15 | ヴァーナリス アールアンドディー リミテッド | インドリル−ピリドン誘導体類 |
| GB0912499D0 (en) * | 2009-07-18 | 2009-08-26 | Vernalis R&D Ltd | Indopyl-pyridone derivatives |
| CN102933572B (zh) | 2010-04-07 | 2015-01-07 | 霍夫曼-拉罗奇有限公司 | 吡唑-4-基-杂环基-甲酰胺化合物及其使用方法 |
| EP2463289A1 (en) * | 2010-11-26 | 2012-06-13 | Almirall, S.A. | Imidazo[1,2-b]pyridazine derivatives as JAK inhibitors |
| BR112014007203A2 (pt) | 2011-09-27 | 2017-06-13 | F.Hoffmann-La Roche Ag | composto, composição farmacêutica, método de tratamento, utilização de um composto, conjunto e invenção |
| GB201201566D0 (en) | 2012-01-30 | 2012-03-14 | Vernalis R&D Ltd | New chemical compounds |
| KR20160099081A (ko) | 2013-07-26 | 2016-08-19 | 업데이트 파마 인코포레이트 | 비산트렌의 치료 효과 개선용 조합 방법 |
| CR20170345A (es) * | 2015-01-28 | 2017-09-29 | Bayer Pharma Aktiengesellchaft | Derivados de 4h-pirrol[3,2-c]piridin-4-ona |
| SG11202005700SA (en) * | 2017-12-19 | 2020-07-29 | Bristol Myers Squibb Co | Amide substituted indole compounds useful as tlr inhibitors |
| KR20210038911A (ko) * | 2018-07-24 | 2021-04-08 | 에피자임, 인코포레이티드 | Smarca2 길항제로서 유용한 피리딘-2-온 화합물 |
| US10253606B1 (en) | 2018-07-27 | 2019-04-09 | Upwing Energy, LLC | Artificial lift |
| US10280721B1 (en) | 2018-07-27 | 2019-05-07 | Upwing Energy, LLC | Artificial lift |
| US10787873B2 (en) | 2018-07-27 | 2020-09-29 | Upwing Energy, LLC | Recirculation isolator for artificial lift and method of use |
| US10370947B1 (en) * | 2018-07-27 | 2019-08-06 | Upwing Energy, LLC | Artificial lift |
| WO2020038460A1 (zh) * | 2018-08-24 | 2020-02-27 | 南京药捷安康生物科技有限公司 | 一种新型的喹啉衍生物抑制剂 |
| US11686161B2 (en) | 2018-12-28 | 2023-06-27 | Upwing Energy, Inc. | System and method of transferring power within a wellbore |
| EP4036086A1 (en) * | 2019-09-24 | 2022-08-03 | Transthera Sciences (Nanjing), Inc. | Heterocyclic derivative and use thereof |
| JP2025523514A (ja) * | 2022-06-24 | 2025-07-23 | エナラーレ セラピューティクス インコーポレイテッド | 神経性換気不全の処置方法 |
| CN115594634B (zh) * | 2022-10-26 | 2024-10-01 | 浙江工业大学 | 一种连续化制备4-硝基吡唑的新工艺 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20030844A2 (en) * | 2001-03-28 | 2005-08-31 | Bristol-Myers Squibb Company | Novel tyrosine kinase inhibitors |
| EP1441725A1 (en) | 2001-10-26 | 2004-08-04 | Aventis Pharmaceuticals Inc. | Benzimidazoles and analogues and their use as protein kinases inhibitors |
| US20050256157A1 (en) * | 2002-08-23 | 2005-11-17 | Chiron Corporation | Combination therapy with CHK1 inhibitors |
| JP2006526654A (ja) | 2003-06-05 | 2006-11-24 | メルク エンド カムパニー インコーポレーテッド | 置換インドールおよび置換インドールの調製方法 |
| TWI372050B (en) * | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| WO2007084135A2 (en) * | 2005-01-28 | 2007-07-26 | Merck & Co., Inc. | Inhibitors of checkpoint kinases |
| EP1891048A1 (en) * | 2005-06-11 | 2008-02-27 | Vernalis (R&D) Limited | Pyrazole-substituted benzimidazole derivatives for use in the treatment of cancer and autoimmune disorders |
| WO2008007122A2 (en) * | 2006-07-14 | 2008-01-17 | Astex Therapeutics Limited | Combinations of pyrazole derivatives for the inhibition of cdks and gsk's |
| WO2008025526A1 (en) | 2006-08-31 | 2008-03-06 | F. Hoffmann-La Roche Ag | Indole derivatives, their manufacture and use as pharmaceutical agents |
| JP5386508B2 (ja) | 2008-01-22 | 2014-01-15 | ヴァーナリス アールアンドディー リミテッド | インドリル−ピリドン誘導体類 |
| US8778972B2 (en) * | 2009-05-15 | 2014-07-15 | Novartis Ag | 5-pyridin-3-yl-1, 3-dihydro-indol-2-on derivatives and their use as modulators of aldosterone synthase and/or CYP11B1 |
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| ES2461799T3 (es) | 2014-05-21 |
| BRPI0906495A8 (pt) | 2015-10-06 |
| BRPI0906495B1 (pt) | 2020-11-10 |
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