UA77799C2 - Process for preparation of 7-substituted-3-quinolinecarbonitriles - Google Patents
Process for preparation of 7-substituted-3-quinolinecarbonitriles Download PDFInfo
- Publication number
- UA77799C2 UA77799C2 UA20041109740A UA20041109740A UA77799C2 UA 77799 C2 UA77799 C2 UA 77799C2 UA 20041109740 A UA20041109740 A UA 20041109740A UA 20041109740 A UA20041109740 A UA 20041109740A UA 77799 C2 UA77799 C2 UA 77799C2
- Authority
- UA
- Ukraine
- Prior art keywords
- methoxy
- amino
- quinolinecarbonitrile
- methoxyphenyl
- dichloro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 78
- 238000002360 preparation method Methods 0.000 title abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- JCGQIVMIQPTWGQ-UHFFFAOYSA-N 7-fluoro-4-oxo-1h-quinoline-3-carbonitrile Chemical compound FC1=CC=C2C(O)=C(C#N)C=NC2=C1 JCGQIVMIQPTWGQ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 156
- -1 7-substituted-3-quinolinecarbonitrile Chemical class 0.000 claims description 86
- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical compound C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 claims description 55
- 125000004432 carbon atom Chemical group C* 0.000 claims description 41
- 150000001875 compounds Chemical class 0.000 claims description 34
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 32
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 24
- 230000003993 interaction Effects 0.000 claims description 24
- 239000012312 sodium hydride Substances 0.000 claims description 24
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical group ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 14
- 239000011734 sodium Substances 0.000 claims description 14
- 229910052708 sodium Inorganic materials 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 11
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 238000007796 conventional method Methods 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Chemical group 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 229910052717 sulfur Chemical group 0.000 claims description 9
- 239000011593 sulfur Chemical group 0.000 claims description 9
- SFDZUJYVIBHPBB-UHFFFAOYSA-N 7-(2-methoxyethoxy)-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N1C=C(C#N)C(=O)C=2C1=CC(OCCOC)=CC=2 SFDZUJYVIBHPBB-UHFFFAOYSA-N 0.000 claims description 8
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 230000002140 halogenating effect Effects 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 125000006413 ring segment Chemical group 0.000 claims description 7
- CRDISMZBOJPSJG-UHFFFAOYSA-N 7-fluoroquinoline-3-carbonitrile Chemical compound C1=C(C#N)C=NC2=CC(F)=CC=C21 CRDISMZBOJPSJG-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000006308 propyl amino group Chemical group 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims description 3
- 229910000105 potassium hydride Inorganic materials 0.000 claims description 3
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 claims description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims 3
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 208000016066 Venous thoracic outlet syndrome Diseases 0.000 claims 1
- 229910052754 neon Inorganic materials 0.000 claims 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 12
- 206010028980 Neoplasm Diseases 0.000 abstract description 7
- 201000011510 cancer Diseases 0.000 abstract description 7
- 102000001253 Protein Kinase Human genes 0.000 abstract description 5
- 108060006633 protein kinase Proteins 0.000 abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 145
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 86
- 239000000203 mixture Substances 0.000 description 71
- 238000004458 analytical method Methods 0.000 description 66
- 239000011541 reaction mixture Substances 0.000 description 56
- 229940093499 ethyl acetate Drugs 0.000 description 47
- 235000019439 ethyl acetate Nutrition 0.000 description 47
- 239000012265 solid product Substances 0.000 description 47
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- 238000001914 filtration Methods 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 238000001819 mass spectrum Methods 0.000 description 26
- 238000010992 reflux Methods 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 238000000746 purification Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 12
- 229940093475 2-ethoxyethanol Drugs 0.000 description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 10
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 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 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 238000012746 preparative thin layer chromatography Methods 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000000908 ammonium hydroxide Substances 0.000 description 8
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 7
- 239000006184 cosolvent Substances 0.000 description 7
- 150000002500 ions Chemical class 0.000 description 7
- 239000012047 saturated solution Substances 0.000 description 7
- 238000001665 trituration Methods 0.000 description 7
- AJROJTARXSATEB-UHFFFAOYSA-N 2,4-dichloro-5-methoxyaniline Chemical compound COC1=CC(N)=C(Cl)C=C1Cl AJROJTARXSATEB-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 6
- BOQICIDBVOCNQA-UHFFFAOYSA-N 7-fluoro-6-methoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N1C=C(C#N)C(=O)C2=C1C=C(F)C(OC)=C2 BOQICIDBVOCNQA-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000004305 biphenyl Substances 0.000 description 5
- 235000010290 biphenyl Nutrition 0.000 description 5
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 5
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- KUZHHJMAZRISHC-UHFFFAOYSA-N 4-chloro-7-fluoro-6-(2-methoxyethoxy)quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(F)C(OCCOC)=CC2=C1Cl KUZHHJMAZRISHC-UHFFFAOYSA-N 0.000 description 4
- HQWUPLKDABZELG-UHFFFAOYSA-N 4-chloro-7-fluoro-6-hydroxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(F)C(O)=CC2=C1Cl HQWUPLKDABZELG-UHFFFAOYSA-N 0.000 description 4
- PNVRUIFACIJUKH-UHFFFAOYSA-N 4-chloro-7-fluoro-6-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(F)C(OC)=CC2=C1Cl PNVRUIFACIJUKH-UHFFFAOYSA-N 0.000 description 4
- CKIFZMDHCWPBKW-UHFFFAOYSA-N 7-fluoro-6-methoxy-4-oxo-1h-quinoline-3-carboxylic acid Chemical compound OC(=O)C1=CN=C2C=C(F)C(OC)=CC2=C1O CKIFZMDHCWPBKW-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-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
- 150000001448 anilines Chemical class 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- KTMGNAIGXYODKQ-VOTSOKGWSA-N ethyl (e)-2-cyano-3-ethoxyprop-2-enoate Chemical compound CCO\C=C(/C#N)C(=O)OCC KTMGNAIGXYODKQ-VOTSOKGWSA-N 0.000 description 4
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- RAOQBDPJGWLCFC-UHFFFAOYSA-N 2-fluoro-1-(2-methoxyethoxy)-4-nitrobenzene Chemical compound COCCOC1=CC=C([N+]([O-])=O)C=C1F RAOQBDPJGWLCFC-UHFFFAOYSA-N 0.000 description 3
- GOQSFGSVUBLEDE-UHFFFAOYSA-N 3-fluoro-4-(2-methoxyethoxy)aniline Chemical compound COCCOC1=CC=C(N)C=C1F GOQSFGSVUBLEDE-UHFFFAOYSA-N 0.000 description 3
- GTLYXWJUDZLUTJ-UHFFFAOYSA-N 4-chloro-6-methoxy-7-(4-methylpiperazin-1-yl)quinoline-3-carbonitrile Chemical compound COC1=CC2=C(Cl)C(C#N)=CN=C2C=C1N1CCN(C)CC1 GTLYXWJUDZLUTJ-UHFFFAOYSA-N 0.000 description 3
- NKNHPOUWDIAROH-UHFFFAOYSA-N 4-chloro-7-(2-methoxyethoxy)quinoline-3-carbonitrile Chemical compound ClC1=C(C#N)C=NC2=CC(OCCOC)=CC=C21 NKNHPOUWDIAROH-UHFFFAOYSA-N 0.000 description 3
- MOVXGKOHTWJWEA-UHFFFAOYSA-N 4-chloro-7-fluoro-6-(2-morpholin-4-ylethoxy)quinoline-3-carbonitrile Chemical compound FC1=CC2=NC=C(C#N)C(Cl)=C2C=C1OCCN1CCOCC1 MOVXGKOHTWJWEA-UHFFFAOYSA-N 0.000 description 3
- GLDPOBFSPURDRC-UHFFFAOYSA-N 4-chloro-7-fluoroquinoline-3-carbonitrile Chemical compound ClC1=C(C#N)C=NC2=CC(F)=CC=C21 GLDPOBFSPURDRC-UHFFFAOYSA-N 0.000 description 3
- NJBZOGXZFBSRIS-UHFFFAOYSA-N 7-fluoro-6-methoxy-4-oxo-1h-quinoline-3-carboxamide Chemical compound N1C=C(C(N)=O)C(=O)C2=C1C=C(F)C(OC)=C2 NJBZOGXZFBSRIS-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
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- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- FUJNUQDCBRIKRF-UHFFFAOYSA-N ethyl 7-fluoro-6-methoxy-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(F)C(OC)=CC2=C(O)C(C(=O)OCC)=CN=C21 FUJNUQDCBRIKRF-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- UMJJFEIKYGFCAT-UHFFFAOYSA-N indan-2-one Chemical compound C1=CC=C2CC(=O)CC2=C1 UMJJFEIKYGFCAT-UHFFFAOYSA-N 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- ROTONRWJLXYJBD-UHFFFAOYSA-N oxan-2-ylmethanol Chemical compound OCC1CCCCO1 ROTONRWJLXYJBD-UHFFFAOYSA-N 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- DMTUQTRZIMTUQV-UHFFFAOYSA-N potassium;ethenylideneazanide Chemical compound [K+].[CH2-]C#N DMTUQTRZIMTUQV-UHFFFAOYSA-N 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- ZPHGMBGIFODUMF-UHFFFAOYSA-N thiophen-2-ylmethanol Chemical compound OCC1=CC=CS1 ZPHGMBGIFODUMF-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
-
- 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
-
- 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
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/12—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 chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37645602P | 2002-04-30 | 2002-04-30 | |
| PCT/US2003/013149 WO2003093241A1 (en) | 2002-04-30 | 2003-04-29 | Process for the preparation of 7-substituted-3-quinoline and 3-quinol-4-one carbonitriles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA77799C2 true UA77799C2 (en) | 2007-01-15 |
Family
ID=29401349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA20041109740A UA77799C2 (en) | 2002-04-30 | 2003-04-29 | Process for preparation of 7-substituted-3-quinolinecarbonitriles |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US6780996B2 (es) |
| EP (1) | EP1499594B1 (es) |
| JP (1) | JP2005529907A (es) |
| KR (1) | KR20040106420A (es) |
| CN (1) | CN100354263C (es) |
| AR (1) | AR039776A1 (es) |
| AT (1) | ATE302191T1 (es) |
| AU (1) | AU2003231162B2 (es) |
| BR (1) | BR0309712A (es) |
| CA (1) | CA2483529A1 (es) |
| CO (1) | CO5631435A2 (es) |
| CR (1) | CR7511A (es) |
| DE (1) | DE60301350T2 (es) |
| DK (1) | DK1499594T3 (es) |
| EC (1) | ECSP045406A (es) |
| ES (1) | ES2243903T3 (es) |
| HK (1) | HK1070358A1 (es) |
| IL (1) | IL164851A0 (es) |
| MX (1) | MXPA04010664A (es) |
| NO (1) | NO20044533L (es) |
| NZ (1) | NZ536141A (es) |
| RU (1) | RU2309149C2 (es) |
| SI (1) | SI1499594T1 (es) |
| TW (1) | TWI275390B (es) |
| UA (1) | UA77799C2 (es) |
| WO (1) | WO2003093241A1 (es) |
| ZA (1) | ZA200409639B (es) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060167021A1 (en) * | 2002-10-04 | 2006-07-27 | Caritas St. Elizabeth's Medical Center Of Boston, Inc. | Inhibition of src for treatment of reperfusion injury related to revascularization |
| US20040229880A1 (en) * | 2003-02-21 | 2004-11-18 | Wyeth | 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-alkoxy-3-quinolinecarbonitriles for the treatment of ischemic injury |
| AU2004289243B2 (en) * | 2003-11-06 | 2010-07-22 | Wyeth Llc | 4-anilino-3-quinolinecarbonitriles for the treatment of chronic myelogenous leukemia (CML) |
| FR2862301B1 (fr) * | 2003-11-17 | 2007-12-21 | Aventis Pharma Sa | Nouveau procede de preparation de quinoleines 3-fluorees |
| TW200529846A (en) * | 2004-02-20 | 2005-09-16 | Wyeth Corp | 3-quinolinecarbonitrile protein kinase inhibitors |
| KR20070085413A (ko) * | 2004-10-22 | 2007-08-27 | 와이어쓰 | 허혈 손상 치료용4-[(2,4-디클로로-5-메톡시페닐)아미노]-6-알콕시-7-에티닐-3-퀴놀린카르보니트릴 |
| NZ556673A (en) | 2005-02-03 | 2010-03-26 | Gen Hospital Corp | Method for treating gefitinib and/or erlotinib resistant cancer with an EGFR inhibitor |
| AU2006247520A1 (en) * | 2005-05-18 | 2006-11-23 | Wyeth | 3-cyanoquinoline inhibitors of TPL2 kinase and methods of making and using the same |
| EP1896020B1 (en) | 2005-06-17 | 2014-08-20 | The Board of Regents of The University of Texas System | SKI 606 as src kinase inhibitor for treating osteolytic lesions |
| EP1902029B2 (en) * | 2005-07-01 | 2022-02-16 | Wyeth LLC | Crystalline forms of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarb-onitrile and methods of preparing the same |
| KR101354828B1 (ko) | 2005-11-04 | 2014-02-18 | 와이어쓰 엘엘씨 | ｍＴＯＲ 저해자, 헤르셉틴, 및/또는 ＨＫＩ-272의항신생물성 조합 |
| TW200808728A (en) * | 2006-05-23 | 2008-02-16 | Wyeth Corp | Method of preparing 4-halogenated quinoline intermediates |
| WO2008060283A1 (en) * | 2006-11-16 | 2008-05-22 | Wyeth | 4-anilino-3-quinolinecarbonitriles for the treatment of acute myelogenous leukemia (aml) |
| US20080119463A1 (en) * | 2006-11-16 | 2008-05-22 | Wyeth | 4-Anilino-3-quinolinecarbonitriles for the treatment of acute myelogenous leukemia (AML) |
| SI3002009T1 (sl) | 2007-06-01 | 2021-09-30 | Wyeth Llc | Zdravljenje kronične mieloične levkemije, ki je odporna na imatinib, ki ima mutacijo 1457t>c na genu bcrabl, s pomočjo sestavine bosutinib |
| US8022216B2 (en) | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
| CN101602687A (zh) * | 2008-06-13 | 2009-12-16 | 上海特化医药科技有限公司 | 6-硝基苯乙酮类化合物、其制备方法及用途 |
| EP3730139B1 (en) | 2008-06-17 | 2023-08-16 | Wyeth LLC | Antineoplastic combinations containing hki-272 and vinorelbine |
| KR101434009B1 (ko) | 2008-08-04 | 2014-08-25 | 와이어쓰 엘엘씨 | 4-아닐리노-3-사이아노퀴놀린과 카페시타빈의 항신생물성 조합물 |
| WO2010030835A2 (en) * | 2008-09-11 | 2010-03-18 | Wyeth Llc | Pharmaceutical compositions of an src kinase inhibitor and an aromatase inhibitor |
| CN101723854A (zh) | 2008-10-24 | 2010-06-09 | 上海特化医药科技有限公司 | 6-取代氨基-3-氰基喹啉类化合物的制备方法及其中间体 |
| JP5992325B2 (ja) | 2009-04-06 | 2016-09-14 | ワイス・エルエルシー | 乳癌のための、ネラチニブを活用する治療計画 |
| UY33236A (es) | 2010-02-25 | 2011-09-30 | Novartis Ag | Inhibidores dimericos de las iap |
| ES2639407T3 (es) | 2010-06-09 | 2017-10-26 | Tianjin Hemay Oncology Pharmaceutical Co., Ltd. | Derivados de cianoquinolina |
| CN103261186A (zh) | 2010-12-13 | 2013-08-21 | 诺瓦提斯公司 | 二聚化iap抑制剂 |
| UY33794A (es) | 2010-12-13 | 2012-07-31 | Novartis Ag | Inhibidores diméricos de las iap |
| EP2680844B1 (en) | 2011-03-04 | 2016-10-19 | GlaxoSmithKline Intellectual Property Development Limited | Amino-quinolines as kinase inhibitors |
| WO2013008217A1 (en) | 2011-07-13 | 2013-01-17 | Novartis Ag | 4 - piperidinyl compounds for use as tankyrase inhibitors |
| JP2014520858A (ja) | 2011-07-13 | 2014-08-25 | ノバルティス アーゲー | タンキラーゼ阻害剤として用いるための新規な２−ピペリジン−１−イル−アセトアミド化合物 |
| CN103814032A (zh) | 2011-07-13 | 2014-05-21 | 诺华股份有限公司 | 用作端锚聚合酶抑制剂的4-氧代-3,5,7,8-四氢-4H-吡喃并[4,3-d]嘧啶基化合物 |
| TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
| AU2013208720A1 (en) | 2012-01-09 | 2014-07-24 | Arrowhead Research Corporation | RNAi agents to treat Beta-Catenin related diseases |
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| CN103804353A (zh) * | 2012-11-01 | 2014-05-21 | 常辉 | 一类治疗精神分裂症的化合物及其用途 |
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| AU2014219283C1 (en) | 2013-02-19 | 2016-10-27 | Novartis Ag | Benzothiophene derivatives and compositions thereof as selective estrogen receptor degraders |
| ES2831625T3 (es) | 2013-02-20 | 2021-06-09 | Kala Pharmaceuticals Inc | Compuestos terapéuticos y sus usos |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| RU2662810C2 (ru) | 2013-02-21 | 2018-07-31 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Хиназолины в качестве ингибиторов киназы |
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| ZA9756B (en) * | 1996-01-16 | 1997-07-17 | Warner Lambert Co | Process for preparing 4,6-disubstituted pyrido[3,4-d]-pyrimidines |
| US6002008A (en) | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
| UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
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| US6638929B2 (en) * | 1999-12-29 | 2003-10-28 | Wyeth | Tricyclic protein kinase inhibitors |
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| JP4326328B2 (ja) * | 2001-07-16 | 2009-09-02 | アストラゼネカ アクチボラグ | キノリン誘導体及びそれらのチロシンキナーゼ阻害薬としての使用 |
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