AU2003276125B2 - Chemical process - Google Patents
Chemical process Download PDFInfo
- Publication number
- AU2003276125B2 AU2003276125B2 AU2003276125A AU2003276125A AU2003276125B2 AU 2003276125 B2 AU2003276125 B2 AU 2003276125B2 AU 2003276125 A AU2003276125 A AU 2003276125A AU 2003276125 A AU2003276125 A AU 2003276125A AU 2003276125 B2 AU2003276125 B2 AU 2003276125B2
- Authority
- AU
- Australia
- Prior art keywords
- formula
- compound
- alkyl
- hydrogen
- methyl
- 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.)
- Ceased
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- 238000001311 chemical methods and process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 142
- 238000000034 method Methods 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- -1 aralkoxy Chemical group 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 18
- 229940100198 alkylating agent Drugs 0.000 claims description 15
- 239000002168 alkylating agent Substances 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- JHGRUPGVUMAQQU-UHFFFAOYSA-N 2,3-dimethyl-6-nitroindazole Chemical compound C1=C([N+]([O-])=O)C=CC2=C(C)N(C)N=C21 JHGRUPGVUMAQQU-UHFFFAOYSA-N 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000001769 aryl amino group Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 238000009833 condensation Methods 0.000 claims description 7
- 230000005494 condensation Effects 0.000 claims description 7
- KTPBKMYOIFHJMI-UHFFFAOYSA-N 5-amino-2-methylbenzenesulfonamide Chemical compound CC1=CC=C(N)C=C1S(N)(=O)=O KTPBKMYOIFHJMI-UHFFFAOYSA-N 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 239000000203 mixture Substances 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 42
- 150000003839 salts Chemical class 0.000 description 38
- 235000002639 sodium chloride Nutrition 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 36
- 238000001819 mass spectrum Methods 0.000 description 33
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 32
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000000047 product Substances 0.000 description 29
- 239000012453 solvate Substances 0.000 description 29
- 239000002904 solvent Substances 0.000 description 29
- 235000019439 ethyl acetate Nutrition 0.000 description 28
- 239000000543 intermediate Substances 0.000 description 28
- 230000000694 effects Effects 0.000 description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 23
- 230000002829 reductive effect Effects 0.000 description 23
- 239000008194 pharmaceutical composition Substances 0.000 description 22
- 238000011282 treatment Methods 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- 206010028980 Neoplasm Diseases 0.000 description 20
- 208000035475 disorder Diseases 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 18
- 201000011510 cancer Diseases 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 229910001868 water Inorganic materials 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 230000033115 angiogenesis Effects 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- 239000003112 inhibitor Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 13
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 13
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- 238000001914 filtration Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 241000124008 Mammalia Species 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 239000002002 slurry Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 10
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 108091008605 VEGF receptors Proteins 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 230000002491 angiogenic effect Effects 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 238000000132 electrospray ionisation Methods 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 230000002159 abnormal effect Effects 0.000 description 8
- 125000002947 alkylene group Chemical group 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 6
- 125000004647 alkyl sulfenyl group Chemical group 0.000 description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 230000029936 alkylation Effects 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 6
- 229940034982 antineoplastic agent Drugs 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 6
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- XJQWZUJNHLGBQG-UHFFFAOYSA-N 1-(methylsulfonylmethyl)-4-nitrobenzene Chemical compound CS(=O)(=O)CC1=CC=C([N+]([O-])=O)C=C1 XJQWZUJNHLGBQG-UHFFFAOYSA-N 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- 102000009465 Growth Factor Receptors Human genes 0.000 description 5
- 108010009202 Growth Factor Receptors Proteins 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
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- 201000010099 disease Diseases 0.000 description 5
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- 239000007788 liquid Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 125000004043 oxo group Chemical group O=* 0.000 description 5
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
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- 239000000314 lubricant Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- DVGMRZQSSNNTFY-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-n,2,3-trimethylindazol-6-amine Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C1=CC=NC(Cl)=N1 DVGMRZQSSNNTFY-UHFFFAOYSA-N 0.000 description 4
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
- PVNVSSNARYHLRF-UHFFFAOYSA-N 2,3-dimethylindazol-6-amine Chemical compound C1=C(N)C=CC2=C(C)N(C)N=C21 PVNVSSNARYHLRF-UHFFFAOYSA-N 0.000 description 3
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 3
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
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- QDNCLIPKBNMUPP-UHFFFAOYSA-N trimethyloxidanium Chemical compound C[O+](C)C QDNCLIPKBNMUPP-UHFFFAOYSA-N 0.000 description 3
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- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
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- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
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- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
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- 229940082509 xanthan gum Drugs 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38934902P | 2002-06-17 | 2002-06-17 | |
| US60/389,349 | 2002-06-17 | ||
| PCT/US2003/019211 WO2003106416A2 (en) | 2002-06-17 | 2003-06-17 | Chemical process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2003276125A1 AU2003276125A1 (en) | 2003-12-31 |
| AU2003276125B2 true AU2003276125B2 (en) | 2007-05-17 |
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Family Applications (1)
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|---|---|---|---|
| AU2003276125A Ceased AU2003276125B2 (en) | 2002-06-17 | 2003-06-17 | Chemical process |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20060252943A1 (enExample) |
| EP (1) | EP1515955A4 (enExample) |
| JP (1) | JP2005529954A (enExample) |
| CN (1) | CN1688553A (enExample) |
| AU (1) | AU2003276125B2 (enExample) |
| CA (1) | CA2489648A1 (enExample) |
| IL (1) | IL165286A0 (enExample) |
| MX (1) | MXPA04012860A (enExample) |
| PL (1) | PL374963A1 (enExample) |
| WO (1) | WO2003106416A2 (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| ATE451104T1 (de) | 2002-07-29 | 2009-12-15 | Rigel Pharmaceuticals Inc | Verfahren zur behandlung oder pruvention von autoimmunkrankheiten mit 2,4-pyrimidindiamin- verbindungen |
| KR20050122220A (ko) | 2003-03-25 | 2005-12-28 | 다케다 샌디에고, 인코포레이티드 | 디펩티딜 펩티다제 억제제 |
| ES2421139T3 (es) | 2003-07-30 | 2013-08-29 | Rigel Pharmaceuticals, Inc. | Compuestos de 2,4-pirimidindiamina para su uso en el tratamiento o la prevención de enfermedades autoinmunitarias |
| KR20060041309A (ko) | 2003-08-13 | 2006-05-11 | 다케다 야쿠힌 고교 가부시키가이샤 | ４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도 |
| WO2005019345A1 (ja) | 2003-08-25 | 2005-03-03 | Kaneka Corporation | 耐熱性の改善された硬化性組成物 |
| US7790734B2 (en) | 2003-09-08 | 2010-09-07 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| EA013427B1 (ru) | 2004-03-15 | 2010-04-30 | Такеда Фармасьютикал Компани Лимитед | Ингибиторы дипептидилпептидазы |
| WO2006020564A1 (en) * | 2004-08-09 | 2006-02-23 | Smithkline Beecham Corporation | Pyrimidin derivatives for the treatment of multiple myeloma |
| EP1828192B1 (en) | 2004-12-21 | 2014-12-03 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| EP2161275A1 (en) | 2005-01-19 | 2010-03-10 | Rigel Pharmaceuticals, Inc. | Prodrugs of 2,4-pyrimidinediamine compounds and their uses |
| US20070203161A1 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| US7491732B2 (en) | 2005-06-08 | 2009-02-17 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
| PT1942898E (pt) | 2005-09-14 | 2011-12-20 | Takeda Pharmaceutical | Inibidores da dipeptidilpeptidase para o tratamento da diabetes |
| CN101360723A (zh) | 2005-09-16 | 2009-02-04 | 武田药品工业株式会社 | 制备嘧啶二酮衍生物的方法 |
| SI1954281T1 (sl) | 2005-11-29 | 2011-06-30 | Glaxosmithkline Llc | Postopek zdravljenja raka |
| UA94427C2 (ru) * | 2005-11-29 | 2011-05-10 | Смиткляйн Бичам Корпорейшн | Фармацевтическая композиция для местного лечения неоваскулярных расстройств глаз |
| WO2007098507A2 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| US8324383B2 (en) | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
| TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| US8093236B2 (en) | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
| PL2154967T3 (pl) | 2007-04-16 | 2014-08-29 | Hutchison Medipharma Entpr Ltd | Pochodne pirymidyny |
| CN102066339B (zh) | 2008-04-16 | 2014-09-24 | 波托拉医药品公司 | 作为syk或jak蛋白激酶抑制剂的2，6-二氨基-嘧啶-5-基甲酰胺类化合物 |
| US8138339B2 (en) | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| NZ589315A (en) | 2008-04-16 | 2012-11-30 | Portola Pharm Inc | 2,6-diamino-pyrimidin-5-yl-carboxamides as Spleen tryosine kinase (syk) or Janus kinase (JAK) inhibitors |
| NZ588830A (en) | 2008-04-22 | 2012-11-30 | Portola Pharm Inc | Inhibitors of protein kinases |
| WO2011039648A1 (en) | 2009-09-30 | 2011-04-07 | Glaxo Wellcome Manufacturing Pte Ltd. | Methods of administration and treatment |
| WO2011050159A1 (en) * | 2009-10-23 | 2011-04-28 | Glaxo Wellcome Manufacturing Pte Ltd | Compositions and processes |
| WO2011058179A1 (en) | 2009-11-16 | 2011-05-19 | Ratiopharm Gmbh | 5- (4- (n- (2, 3 -dimethyl- 2h- indazol- 6 -yl) -n-methylamino) pyrimidin- 2 -ylamino) -2 -methylbenzenesulfonamide |
| WO2011069053A1 (en) | 2009-12-04 | 2011-06-09 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of pazopanip hcl and crystalline forms of pazopanib hcl |
| US9102625B2 (en) | 2010-11-01 | 2015-08-11 | Portola Pharmaceuticals, Inc. | Nicotinamides as JAK kinase modulators |
| US20130317029A1 (en) | 2010-11-01 | 2013-11-28 | Portola Pharmaceuticals, Inc. | Oxypyrimidines as syk modulators |
| EP2635556B1 (en) | 2010-11-01 | 2017-06-21 | Portola Pharmaceuticals, Inc. | Benzamides and nicotinamides as syk modulators |
| WO2012073254A1 (en) * | 2010-11-29 | 2012-06-07 | Hetero Research Foundation | A process for the preparation of pazopanib using novel intermediate |
| CN102060848B (zh) * | 2010-12-09 | 2013-09-18 | 天津药物研究院 | 芳香胺取代的嘧啶衍生物的制备及用途 |
| EP2782579B1 (en) | 2011-11-23 | 2019-01-02 | Portola Pharmaceuticals, Inc. | Pyrazine kinase inhibitors |
| CN103319410B (zh) * | 2012-03-22 | 2016-04-06 | 天津药物研究院 | 一种吲唑化合物的合成方法 |
| CN103373989B (zh) * | 2012-04-28 | 2016-04-13 | 上海医药工业研究院 | 盐酸帕唑帕尼的中间体的制备方法 |
| CN103373963B (zh) * | 2012-04-28 | 2015-07-08 | 上海医药工业研究院 | 盐酸帕唑帕尼的中间体及其制备方法 |
| US9676756B2 (en) | 2012-10-08 | 2017-06-13 | Portola Pharmaceuticals, Inc. | Substituted pyrimidinyl kinase inhibitors |
| WO2014097152A1 (en) * | 2012-12-17 | 2014-06-26 | Ranbaxy Laboratories Limited | Process for the preparation of pazopanib or salts thereof |
| US9802923B2 (en) | 2012-12-17 | 2017-10-31 | Sun Pharmaceutical Industries Limited | Process for the preparation of pazopanib or salts thereof |
| CN103232443B (zh) * | 2013-02-01 | 2014-12-10 | 天津药物研究院 | 一种吲唑衍生物的晶型及其制备和用途 |
| CN103450085B (zh) * | 2013-08-15 | 2015-11-18 | 凯莱英医药集团（天津）股份有限公司 | 一种盐酸帕唑帕尼关键中间体的制备方法 |
| WO2015068175A2 (en) * | 2013-11-05 | 2015-05-14 | Laurus Labs Private Limited | An improved process for the preparation of pazopanib or a pharmaceutically acceptable salt thereof |
| CN106565688B (zh) * | 2016-11-11 | 2018-08-31 | 重庆医科大学 | 帕唑帕尼二聚体及其制备方法和用途 |
| CN110028495B (zh) * | 2019-05-24 | 2019-12-03 | 济南爱思医药科技有限公司 | 帕唑帕尼盐酸盐的制备方法 |
| CN116554106A (zh) * | 2023-04-28 | 2023-08-08 | 扬州市普林斯医药科技有限公司 | 一种6-氯-2-甲基-2h-吲唑-5-胺的制备方法 |
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| US3755332A (en) * | 1971-07-01 | 1973-08-28 | Ciba Geigy Corp | Substituted 4 indazolaminoquinolines |
| US20020052386A1 (en) * | 2000-02-17 | 2002-05-02 | Armistead David M. | Kinase inhibitors |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9918035D0 (en) * | 1999-07-30 | 1999-09-29 | Novartis Ag | Organic compounds |
| CA2386218A1 (en) * | 1999-10-07 | 2001-04-12 | Amgen Inc. | Triazine kinase inhibitors |
| JP3711443B2 (ja) * | 2000-10-25 | 2005-11-02 | セイコーエプソン株式会社 | インクジェット式記録装置 |
| ATE430742T1 (de) * | 2000-12-21 | 2009-05-15 | Smithkline Beecham Corp | Pyrimidinamine als angiogenesemodulatoren |
| TWI329105B (en) * | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| GB0206215D0 (en) * | 2002-03-15 | 2002-05-01 | Novartis Ag | Organic compounds |
-
2003
- 2003-06-17 WO PCT/US2003/019211 patent/WO2003106416A2/en not_active Ceased
- 2003-06-17 US US10/518,349 patent/US20060252943A1/en not_active Abandoned
- 2003-06-17 IL IL16528603A patent/IL165286A0/xx unknown
- 2003-06-17 CN CNA038141698A patent/CN1688553A/zh active Pending
- 2003-06-17 AU AU2003276125A patent/AU2003276125B2/en not_active Ceased
- 2003-06-17 EP EP03742050A patent/EP1515955A4/en not_active Withdrawn
- 2003-06-17 PL PL03374963A patent/PL374963A1/xx not_active Application Discontinuation
- 2003-06-17 JP JP2004513249A patent/JP2005529954A/ja active Pending
- 2003-06-17 MX MXPA04012860A patent/MXPA04012860A/es unknown
- 2003-06-17 CA CA002489648A patent/CA2489648A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3755332A (en) * | 1971-07-01 | 1973-08-28 | Ciba Geigy Corp | Substituted 4 indazolaminoquinolines |
| US20020052386A1 (en) * | 2000-02-17 | 2002-05-02 | Armistead David M. | Kinase inhibitors |
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1515955A4 (en) | 2006-05-03 |
| AU2003276125A1 (en) | 2003-12-31 |
| EP1515955A2 (en) | 2005-03-23 |
| CN1688553A (zh) | 2005-10-26 |
| JP2005529954A (ja) | 2005-10-06 |
| MXPA04012860A (es) | 2005-09-20 |
| WO2003106416A3 (en) | 2004-05-06 |
| WO2003106416A2 (en) | 2003-12-24 |
| PL374963A1 (en) | 2005-11-14 |
| US20060252943A1 (en) | 2006-11-09 |
| IL165286A0 (en) | 2005-12-18 |
| CA2489648A1 (en) | 2003-12-24 |
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