EA015574B1 - Триазолиламинопиримидиновые соединения - Google Patents
Триазолиламинопиримидиновые соединения Download PDFInfo
- Publication number
- EA015574B1 EA015574B1 EA200971067A EA200971067A EA015574B1 EA 015574 B1 EA015574 B1 EA 015574B1 EA 200971067 A EA200971067 A EA 200971067A EA 200971067 A EA200971067 A EA 200971067A EA 015574 B1 EA015574 B1 EA 015574B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- ethyl
- mmol
- fluoro
- benzo
- alkyl
- Prior art date
Links
- -1 Triazolyl aminopyrimidine compounds Chemical class 0.000 title claims abstract description 237
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
- 201000011510 cancer Diseases 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 162
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 23
- 239000011737 fluorine Substances 0.000 claims description 23
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 7
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000006525 methoxy ethyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])OC([H])([H])[H] 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- NGZYRKGJWYJGRS-UHFFFAOYSA-N n-methylpyrrolidin-3-amine Chemical compound CNC1CCNC1 NGZYRKGJWYJGRS-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 199
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 189
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 143
- 239000000243 solution Substances 0.000 description 135
- 239000000203 mixture Substances 0.000 description 134
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 124
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 101
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
- 238000002360 preparation method Methods 0.000 description 71
- 239000007787 solid Substances 0.000 description 64
- 229920006395 saturated elastomer Polymers 0.000 description 57
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 55
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- 239000011780 sodium chloride Substances 0.000 description 50
- 125000005605 benzo group Chemical group 0.000 description 45
- 238000000034 method Methods 0.000 description 44
- 238000004440 column chromatography Methods 0.000 description 43
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 42
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 42
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 41
- 229910052938 sodium sulfate Inorganic materials 0.000 description 41
- 235000011152 sodium sulphate Nutrition 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 32
- 239000003921 oil Substances 0.000 description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 239000000543 intermediate Substances 0.000 description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 238000010411 cooking Methods 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- 239000012043 crude product Substances 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 17
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 12
- 238000004811 liquid chromatography Methods 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 229910021529 ammonia Inorganic materials 0.000 description 10
- 239000012141 concentrate Substances 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000000908 ammonium hydroxide Substances 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 229910052740 iodine Inorganic materials 0.000 description 8
- 239000011630 iodine Substances 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000003550 marker Substances 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000010802 sludge Substances 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 230000000394 mitotic effect Effects 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 6
- ZOSIXKLMVJHENK-UHFFFAOYSA-N 5-(bromomethyl)-2-fluoro-4-iodopyridine Chemical compound FC1=CC(I)=C(CBr)C=N1 ZOSIXKLMVJHENK-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000012279 sodium borohydride Substances 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- CHEYEJGXQSHSFE-UHFFFAOYSA-N 2-(triazol-1-yl)ethanamine Chemical compound NCCN1C=CN=N1 CHEYEJGXQSHSFE-UHFFFAOYSA-N 0.000 description 5
- DVJNMERQFYKTEG-UHFFFAOYSA-N 6-fluoro-4-iodopyridin-3-ol Chemical compound OC1=CN=C(F)C=C1I DVJNMERQFYKTEG-UHFFFAOYSA-N 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 5
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 208000029742 colonic neoplasm Diseases 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 108020001507 fusion proteins Proteins 0.000 description 5
- 102000037865 fusion proteins Human genes 0.000 description 5
- 208000006359 hepatoblastoma Diseases 0.000 description 5
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 201000001441 melanoma Diseases 0.000 description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 201000006958 oropharynx cancer Diseases 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 5
- XWYBMCCCOJQFBM-UHFFFAOYSA-N 6-fluoro-4-iodopyridin-3-amine Chemical compound NC1=CN=C(F)C=C1I XWYBMCCCOJQFBM-UHFFFAOYSA-N 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- 206010014733 Endometrial cancer Diseases 0.000 description 4
- 206010014759 Endometrial neoplasm Diseases 0.000 description 4
- 239000005909 Kieselgur Substances 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 4
- 206010031096 Oropharyngeal cancer Diseases 0.000 description 4
- 206010033128 Ovarian cancer Diseases 0.000 description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- 206010060862 Prostate cancer Diseases 0.000 description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 235000011089 carbon dioxide Nutrition 0.000 description 4
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 4
- 201000004101 esophageal cancer Diseases 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 206010017758 gastric cancer Diseases 0.000 description 4
- 208000005017 glioblastoma Diseases 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
- UFEJKYYYVXYMMS-UHFFFAOYSA-N methylcarbamic acid Chemical compound CNC(O)=O UFEJKYYYVXYMMS-UHFFFAOYSA-N 0.000 description 4
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- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 4
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- UKMQGSDZMCVFBC-UHFFFAOYSA-N 1-(6-fluoro-4-iodopyridin-3-yl)ethanol Chemical compound CC(O)C1=CN=C(F)C=C1I UKMQGSDZMCVFBC-UHFFFAOYSA-N 0.000 description 3
- BAXMCVFPJFOSCM-UHFFFAOYSA-N 1-(6-fluoropyridin-3-yl)ethanol Chemical compound CC(O)C1=CC=C(F)N=C1 BAXMCVFPJFOSCM-UHFFFAOYSA-N 0.000 description 3
- NWDIURJMSKKSFV-UHFFFAOYSA-N 1-[4-(1-benzothiophen-7-yl)pyridin-3-yl]ethanamine Chemical compound CC(N)C1=CN=CC=C1C1=CC=CC2=C1SC=C2 NWDIURJMSKKSFV-UHFFFAOYSA-N 0.000 description 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 3
- TWCBACMXWWICMY-UHFFFAOYSA-N 2-(6-fluoro-4-iodopyridin-3-yl)acetonitrile Chemical compound FC1=CC(I)=C(CC#N)C=N1 TWCBACMXWWICMY-UHFFFAOYSA-N 0.000 description 3
- QBCHAVSIELFPPP-UHFFFAOYSA-N 2-chloro-4-iodo-5-(methoxymethoxy)pyridine Chemical compound COCOC1=CN=C(Cl)C=C1I QBCHAVSIELFPPP-UHFFFAOYSA-N 0.000 description 3
- UEHRAKHRJFMBOY-UHFFFAOYSA-N 3-(methoxymethoxy)pyridine Chemical compound COCOC1=CC=CN=C1 UEHRAKHRJFMBOY-UHFFFAOYSA-N 0.000 description 3
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- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
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- 239000008363 phosphate buffer Substances 0.000 description 1
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- 235000011007 phosphoric acid Nutrition 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
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- 108060006633 protein kinase Proteins 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
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- PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 1
- ZZMCISIZXWPJJS-UHFFFAOYSA-N tert-butyl 4-[1-(6-chloro-4-iodopyridin-3-yl)ethyl]piperazine-1-carboxylate Chemical compound C=1N=C(Cl)C=C(I)C=1C(C)N1CCN(C(=O)OC(C)(C)C)CC1 ZZMCISIZXWPJJS-UHFFFAOYSA-N 0.000 description 1
- JJFNIFWNBHFPOX-UHFFFAOYSA-N tert-butyl N-[2-[4-(1-benzothiophen-7-yl)-6-fluoropyridin-3-yl]-2-methylpropyl]carbamate Chemical compound S1C2=C(C=C1)C=CC=C2C1=C(C=NC(=C1)F)C(CNC(OC(C)(C)C)=O)(C)C JJFNIFWNBHFPOX-UHFFFAOYSA-N 0.000 description 1
- MPNFQAUJCISESK-UHFFFAOYSA-N tert-butyl n-(2-fluoroethyl)-n-[1-(6-fluoro-4-iodopyridin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)N(CCF)C(C)C1=CN=C(F)C=C1I MPNFQAUJCISESK-UHFFFAOYSA-N 0.000 description 1
- PGXJXKZUELCAQH-UHFFFAOYSA-N tert-butyl n-[1-(4-iodo-6-methylpyridin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CN=C(C)C=C1I PGXJXKZUELCAQH-UHFFFAOYSA-N 0.000 description 1
- KQSWZIGWXPHDFK-UHFFFAOYSA-N tert-butyl n-[1-(6-chloropyridin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CC=C(Cl)N=C1 KQSWZIGWXPHDFK-UHFFFAOYSA-N 0.000 description 1
- AXUSPXGCUJNNGZ-UHFFFAOYSA-N tert-butyl n-[1-(6-fluoro-4-iodopyridin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CN=C(F)C=C1I AXUSPXGCUJNNGZ-UHFFFAOYSA-N 0.000 description 1
- VASCWXYNPAFMDY-UHFFFAOYSA-N tert-butyl n-[1-(6-methylpyridin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CC=C(C)N=C1 VASCWXYNPAFMDY-UHFFFAOYSA-N 0.000 description 1
- JUNDWJQAMKCXMK-UHFFFAOYSA-N tert-butyl n-[1-[6-chloro-4-[2-[2-[2-(triazol-1-yl)ethylamino]pyrimidin-4-yl]-1-benzothiophen-7-yl]pyridin-3-yl]ethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C(C)C1=CN=C(Cl)C=C1C1=CC=CC2=C1SC(C=1N=C(NCCN3N=NC=C3)N=CC=1)=C2 JUNDWJQAMKCXMK-UHFFFAOYSA-N 0.000 description 1
- MSXKECUMNGTTTR-UHFFFAOYSA-N tert-butyl n-[[4-[2-(2-chloro-5-fluoropyrimidin-4-yl)-1-benzothiophen-7-yl]-6-fluoropyridin-3-yl]methyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(Cl)N=1)F)=C2 MSXKECUMNGTTTR-UHFFFAOYSA-N 0.000 description 1
- JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 1
- GMRIOAVKKGNMMV-UHFFFAOYSA-N tetrabutylazanium;azide Chemical compound [N-]=[N+]=[N-].CCCC[N+](CCCC)(CCCC)CCCC GMRIOAVKKGNMMV-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
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- DUNKXUFBGCUVQW-UHFFFAOYSA-J zirconium tetrachloride Chemical compound Cl[Zr](Cl)(Cl)Cl DUNKXUFBGCUVQW-UHFFFAOYSA-J 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93833307P | 2007-05-16 | 2007-05-16 | |
| PCT/US2008/062799 WO2008144222A2 (en) | 2007-05-16 | 2008-05-07 | Triazolyl aminopyrimidine compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200971067A1 EA200971067A1 (ru) | 2010-04-30 |
| EA015574B1 true EA015574B1 (ru) | 2011-10-31 |
Family
ID=39967594
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200971067A EA015574B1 (ru) | 2007-05-16 | 2008-05-07 | Триазолиламинопиримидиновые соединения |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8114872B2 (enExample) |
| EP (1) | EP2155735A2 (enExample) |
| JP (1) | JP5204838B2 (enExample) |
| KR (1) | KR101131254B1 (enExample) |
| CN (1) | CN101679396B (enExample) |
| AR (1) | AR066472A1 (enExample) |
| AU (1) | AU2008254318B2 (enExample) |
| BR (1) | BRPI0811611A2 (enExample) |
| CA (1) | CA2687474A1 (enExample) |
| CL (1) | CL2008001322A1 (enExample) |
| EA (1) | EA015574B1 (enExample) |
| MX (1) | MX2009012233A (enExample) |
| PE (1) | PE20090803A1 (enExample) |
| TW (1) | TW200902012A (enExample) |
| WO (1) | WO2008144222A2 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010513553A (ja) | 2006-12-21 | 2010-04-30 | イーライ リリー アンド カンパニー | 癌治療用イミダゾリジノニルアミノピリミジン化合物 |
| CN101563342B (zh) | 2006-12-21 | 2012-09-05 | 伊莱利利公司 | 用于治疗癌症的咪唑啉酮基氨基嘧啶化合物 |
| MX2009012228A (es) * | 2007-05-16 | 2009-12-01 | Lilly Co Eli | Compuesto de triazolil aminopirimidina. |
| EA015574B1 (ru) | 2007-05-16 | 2011-10-31 | Эли Лилли Энд Компани | Триазолиламинопиримидиновые соединения |
| MX374634B (es) | 2013-04-15 | 2025-03-06 | Fmc Corp Star | Amidas fungicidas. |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989007599A2 (en) * | 1988-02-09 | 1989-08-24 | Georgia State University Foundation, Inc. | Novel diazines and their method of preparation |
| WO2006066172A1 (en) * | 2004-12-17 | 2006-06-22 | Amgen, Inc. | Aminopyrimidine compounds and methods of use |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004063192A1 (en) | 2003-01-10 | 2004-07-29 | Pharmacopeia Drug Discovery, Inc. | Imidazolyl pyrimidine derivatives useful as il-8 receptor modulators |
| GB0308466D0 (en) | 2003-04-11 | 2003-05-21 | Novartis Ag | Organic compounds |
| US7521457B2 (en) * | 2004-08-20 | 2009-04-21 | Boehringer Ingelheim International Gmbh | Pyrimidines as PLK inhibitors |
| JP2008510771A (ja) * | 2004-08-27 | 2008-04-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ジヒドロプテリジノン、その製造方法および医薬薬剤としてのその使用 |
| TW200800201A (en) | 2005-11-18 | 2008-01-01 | Lilly Co Eli | Pyrimidinyl benzothiophene compounds |
| US8008481B2 (en) | 2006-03-31 | 2011-08-30 | Ericsson Anna M | Indazole compounds |
| CN101563342B (zh) | 2006-12-21 | 2012-09-05 | 伊莱利利公司 | 用于治疗癌症的咪唑啉酮基氨基嘧啶化合物 |
| MX2009012228A (es) | 2007-05-16 | 2009-12-01 | Lilly Co Eli | Compuesto de triazolil aminopirimidina. |
| EA015574B1 (ru) | 2007-05-16 | 2011-10-31 | Эли Лилли Энд Компани | Триазолиламинопиримидиновые соединения |
-
2008
- 2008-05-07 EA EA200971067A patent/EA015574B1/ru not_active IP Right Cessation
- 2008-05-07 CL CL2008001322A patent/CL2008001322A1/es unknown
- 2008-05-07 AR ARP080101931A patent/AR066472A1/es unknown
- 2008-05-07 US US12/596,957 patent/US8114872B2/en not_active Expired - Fee Related
- 2008-05-07 CN CN2008800159078A patent/CN101679396B/zh not_active Expired - Fee Related
- 2008-05-07 TW TW097116887A patent/TW200902012A/zh unknown
- 2008-05-07 JP JP2010508499A patent/JP5204838B2/ja not_active Expired - Fee Related
- 2008-05-07 EP EP08755094A patent/EP2155735A2/en not_active Withdrawn
- 2008-05-07 MX MX2009012233A patent/MX2009012233A/es active IP Right Grant
- 2008-05-07 AU AU2008254318A patent/AU2008254318B2/en not_active Ceased
- 2008-05-07 BR BRPI0811611-3A2A patent/BRPI0811611A2/pt not_active IP Right Cessation
- 2008-05-07 PE PE2008000797A patent/PE20090803A1/es not_active Application Discontinuation
- 2008-05-07 WO PCT/US2008/062799 patent/WO2008144222A2/en not_active Ceased
- 2008-05-07 KR KR1020097023738A patent/KR101131254B1/ko not_active Expired - Fee Related
- 2008-05-07 CA CA2687474A patent/CA2687474A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989007599A2 (en) * | 1988-02-09 | 1989-08-24 | Georgia State University Foundation, Inc. | Novel diazines and their method of preparation |
| WO2006066172A1 (en) * | 2004-12-17 | 2006-06-22 | Amgen, Inc. | Aminopyrimidine compounds and methods of use |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008144222A3 (en) | 2009-01-15 |
| US20100130466A1 (en) | 2010-05-27 |
| MX2009012233A (es) | 2009-12-01 |
| EA200971067A1 (ru) | 2010-04-30 |
| CN101679396B (zh) | 2012-06-06 |
| AU2008254318B2 (en) | 2012-04-05 |
| AU2008254318A1 (en) | 2008-11-27 |
| JP2010527364A (ja) | 2010-08-12 |
| JP5204838B2 (ja) | 2013-06-05 |
| CA2687474A1 (en) | 2008-11-27 |
| US8114872B2 (en) | 2012-02-14 |
| PE20090803A1 (es) | 2009-07-11 |
| CN101679396A (zh) | 2010-03-24 |
| TW200902012A (en) | 2009-01-16 |
| CL2008001322A1 (es) | 2009-05-22 |
| AR066472A1 (es) | 2009-08-19 |
| BRPI0811611A2 (pt) | 2014-11-04 |
| WO2008144222A2 (en) | 2008-11-27 |
| KR101131254B1 (ko) | 2012-04-24 |
| EP2155735A2 (en) | 2010-02-24 |
| KR20090130246A (ko) | 2009-12-21 |
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