AU703328B2 - Aniline derivatives - Google Patents
Aniline derivatives Download PDFInfo
- Publication number
- AU703328B2 AU703328B2 AU38130/95A AU3813095A AU703328B2 AU 703328 B2 AU703328 B2 AU 703328B2 AU 38130/95 A AU38130/95 A AU 38130/95A AU 3813095 A AU3813095 A AU 3813095A AU 703328 B2 AU703328 B2 AU 703328B2
- Authority
- AU
- Australia
- Prior art keywords
- formula
- alkoxy
- alkylamino
- amino
- chloro
- 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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- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 120
- 150000001875 compounds Chemical class 0.000 claims abstract description 111
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000001301 oxygen Substances 0.000 claims abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- -1 hydroxy, amino, hydroxyamino, ureido Chemical group 0.000 claims description 367
- 125000003545 alkoxy group Chemical group 0.000 claims description 138
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 105
- 125000003282 alkyl amino group Chemical group 0.000 claims description 96
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 86
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 83
- 150000001448 anilines Chemical class 0.000 claims description 75
- 150000003839 salts Chemical class 0.000 claims description 66
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- 125000001424 substituent group Chemical group 0.000 claims description 51
- 238000002360 preparation method Methods 0.000 claims description 38
- 125000001153 fluoro group Chemical group F* 0.000 claims description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
- 238000004519 manufacturing process Methods 0.000 claims description 32
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 238000006722 reduction reaction Methods 0.000 claims description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 230000009467 reduction Effects 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 230000001028 anti-proliverative effect Effects 0.000 claims description 17
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 17
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 241001465754 Metazoa Species 0.000 claims description 16
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000002541 furyl group Chemical group 0.000 claims description 11
- 125000002971 oxazolyl group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000000335 thiazolyl group Chemical group 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 10
- 125000001246 bromo group Chemical group Br* 0.000 claims description 10
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 9
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
- 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 description 7
- 230000010933 acylation Effects 0.000 claims description 7
- 238000005917 acylation reaction Methods 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 230000029936 alkylation Effects 0.000 claims description 6
- 238000005804 alkylation reaction Methods 0.000 claims description 6
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
- 125000005605 benzo group Chemical group 0.000 claims description 6
- 230000003647 oxidation Effects 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 5
- 239000005864 Sulphur Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 238000003776 cleavage reaction Methods 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- IOWGWFDLSDBRRB-UHFFFAOYSA-N 6-[3-(dimethylamino)propoxy]-7-methoxy-n-[3-methyl-4-(pyridin-2-ylmethoxy)phenyl]quinazolin-4-amine Chemical compound C=12C=C(OCCCN(C)C)C(OC)=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CC=CC=N1 IOWGWFDLSDBRRB-UHFFFAOYSA-N 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 239000002168 alkylating agent Substances 0.000 claims description 4
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 125000000586 2-(4-morpholinyl)ethoxy group Chemical group [H]C([H])(O*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- JMHHIZUPKQSNEM-UHFFFAOYSA-N 4-n-[2-fluoro-4-(pyridin-2-ylmethoxy)phenyl]-6-n-(2-methoxyethyl)quinazoline-4,6-diamine Chemical compound C12=CC(NCCOC)=CC=C2N=CN=C1NC(C(=C1)F)=CC=C1OCC1=CC=CC=N1 JMHHIZUPKQSNEM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- SJGAVBKBTDJTJK-UHFFFAOYSA-N 7-methoxy-n-[3-methyl-4-(pyridin-2-ylmethoxy)phenyl]-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CC=CC=N1 SJGAVBKBTDJTJK-UHFFFAOYSA-N 0.000 claims description 3
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 2
- IMBFAWKVCSIUTE-UHFFFAOYSA-N 6,7-dimethoxy-n-[3-methyl-4-(1,3-thiazol-2-ylmethoxy)phenyl]quinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=NC=CS1 IMBFAWKVCSIUTE-UHFFFAOYSA-N 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
- 238000006268 reductive amination reaction Methods 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
- 150000003246 quinazolines Chemical class 0.000 claims 1
- 241000894007 species Species 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 27
- 201000011510 cancer Diseases 0.000 abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
- 201000010099 disease Diseases 0.000 abstract description 6
- 230000002062 proliferating effect Effects 0.000 abstract description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 abstract description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 abstract description 2
- 239000011593 sulfur Chemical group 0.000 abstract 1
- 229910052717 sulfur Chemical group 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 251
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- 239000007858 starting material Substances 0.000 description 106
- 239000000243 solution Substances 0.000 description 79
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 78
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 65
- 239000000463 material Substances 0.000 description 60
- 239000000047 product Substances 0.000 description 53
- 238000010992 reflux Methods 0.000 description 53
- 238000012360 testing method Methods 0.000 description 50
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 238000001228 spectrum Methods 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
- 238000000921 elemental analysis Methods 0.000 description 39
- 239000012074 organic phase Substances 0.000 description 37
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 35
- 238000004440 column chromatography Methods 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000003480 eluent Substances 0.000 description 31
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 31
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 20
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 18
- DPHCXXYPSYMICK-UHFFFAOYSA-N 2-chloro-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(Cl)=C1 DPHCXXYPSYMICK-UHFFFAOYSA-N 0.000 description 17
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 241000282414 Homo sapiens Species 0.000 description 16
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 16
- 101800003838 Epidermal growth factor Proteins 0.000 description 15
- 229910052783 alkali metal Inorganic materials 0.000 description 15
- 229940116977 epidermal growth factor Drugs 0.000 description 15
- 239000012258 stirred mixture Substances 0.000 description 15
- 102400001368 Epidermal growth factor Human genes 0.000 description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 13
- 230000002401 inhibitory effect Effects 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- PLTABDMBEVNMMV-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinazoline;hydrochloride Chemical compound Cl.C1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 PLTABDMBEVNMMV-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- 239000003701 inert diluent Substances 0.000 description 10
- 239000012442 inert solvent Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- CJHYXQCMUDJUJX-UHFFFAOYSA-N 3-methyl-4-(pyridin-2-ylmethoxy)aniline Chemical compound CC1=CC(N)=CC=C1OCC1=CC=CC=N1 CJHYXQCMUDJUJX-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 230000012010 growth Effects 0.000 description 9
- 125000006308 propyl amino group Chemical group 0.000 description 9
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 150000001340 alkali metals Chemical class 0.000 description 8
- 239000000908 ammonium hydroxide Substances 0.000 description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 8
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
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- 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
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- 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
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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GB9422866 | 1994-11-12 | ||
GB9422866A GB9422866D0 (en) | 1994-11-12 | 1994-11-12 | Aniline derivatives |
GB9507308 | 1995-04-07 | ||
GBGB9507308.6A GB9507308D0 (en) | 1995-04-07 | 1995-04-07 | Aniline derivatives |
PCT/GB1995/002606 WO1996015118A1 (en) | 1994-11-12 | 1995-11-08 | Aniline derivatives |
Publications (2)
Publication Number | Publication Date |
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AU3813095A AU3813095A (en) | 1996-06-06 |
AU703328B2 true AU703328B2 (en) | 1999-03-25 |
Family
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AU38130/95A Ceased AU703328B2 (en) | 1994-11-12 | 1995-11-08 | Aniline derivatives |
Country Status (16)
Families Citing this family (134)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6645969B1 (en) | 1991-05-10 | 2003-11-11 | Aventis Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase |
TW321649B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
GB9424233D0 (en) * | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
EP0824525B1 (en) * | 1995-04-27 | 2001-06-13 | AstraZeneca AB | Quinazoline derivatives |
GB9508537D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
GB9508565D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
GB9508535D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivative |
GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
GB9514265D0 (en) * | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
US5760041A (en) * | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
US6184225B1 (en) | 1996-02-13 | 2001-02-06 | Zeneca Limited | Quinazoline derivatives as VEGF inhibitors |
GB9603095D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
GB9603097D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline compounds |
KR100489174B1 (ko) | 1996-03-05 | 2005-09-30 | 제네카-파마 소시에떼아노님 | 4-아닐리노퀴나졸린유도체 |
WO1997038983A1 (en) | 1996-04-12 | 1997-10-23 | Warner-Lambert Company | Irreversible inhibitors of tyrosine kinases |
GB9607729D0 (en) * | 1996-04-13 | 1996-06-19 | Zeneca Ltd | Quinazoline derivatives |
CA2258165C (en) | 1996-06-27 | 2009-03-03 | Marc Gaston Venet | N-[4-(heteroarylmethyl)phenyl]-heteroarylamines |
JP4386967B2 (ja) | 1996-07-13 | 2009-12-16 | グラクソ、グループ、リミテッド | プロテインチロシンキナーゼ阻害剤としての縮合複素環式化合物 |
HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
DE19642529A1 (de) | 1996-10-15 | 1998-04-16 | Bayer Ag | Aminophenolderivate |
US6002008A (en) * | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
ATE366250T1 (de) | 1997-04-25 | 2007-07-15 | Janssen Pharmaceutica Nv | Chinazolinone die farnesyltransferase hemmen |
US5929080A (en) * | 1997-05-06 | 1999-07-27 | American Cyanamid Company | Method of treating polycystic kidney disease |
DK0980244T3 (da) * | 1997-05-06 | 2003-09-29 | Wyeth Corp | Anvendelse af quinazoline forbindelser til behandling af polycystisk nyresygdom |
ZA986732B (en) * | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitiors of tyrosine kinases |
US6251912B1 (en) | 1997-08-01 | 2001-06-26 | American Cyanamid Company | Substituted quinazoline derivatives |
TW436485B (en) * | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
US6294532B1 (en) | 1997-08-22 | 2001-09-25 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
US6323209B1 (en) | 1997-11-06 | 2001-11-27 | American Cyanamid Company | Method of treating or inhibiting colonic polyps |
RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
GB9800575D0 (en) * | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
DE69939864D1 (de) | 1998-01-29 | 2008-12-18 | Amgen Inc | Ppar-gamma modulatoren |
US6583157B2 (en) | 1998-01-29 | 2003-06-24 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
US6706721B1 (en) * | 1998-04-29 | 2004-03-16 | Osi Pharmaceuticals, Inc. | N-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate anhydrate and monohydrate |
EP1082311A1 (en) | 1998-05-28 | 2001-03-14 | Parker Hughes Institute | Quinazolines for treating brain tumor |
US6384223B1 (en) | 1998-07-30 | 2002-05-07 | American Home Products Corporation | Substituted quinazoline derivatives |
US6258820B1 (en) | 1999-03-19 | 2001-07-10 | Parker Hughes Institute | Synthesis and anti-tumor activity of 6,7-dialkoxy-4-phenylamino-quinazolines |
US7049410B2 (en) * | 1999-05-14 | 2006-05-23 | Majumdar Adhip P N | Antibodies to a novel EGF-receptor related protein (ERRP) |
WO2000069909A1 (en) | 1999-05-14 | 2000-11-23 | The United States Of America Through The Department Of Veterans Affairs | Isolation and characterization of epidermal growth factor related protein |
NZ530833A (en) * | 1999-06-30 | 2005-08-26 | Tularik Inc | Compounds for the modulation of PPARgamma activity |
US7041691B1 (en) | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
US6933299B1 (en) | 1999-07-09 | 2005-08-23 | Smithkline Beecham Corporation | Anilinoquinazolines as protein tyrosine kinase inhibitors |
ES2295035T3 (es) * | 1999-07-09 | 2008-04-16 | Glaxo Group Limited | Anilinoquinazolinas como inhibidores de proteina tirosina quinasa. |
WO2001021596A1 (en) * | 1999-09-21 | 2001-03-29 | Astrazeneca Ab | Quinazoline derivatives and their use as pharmaceuticals |
PL354923A1 (en) | 1999-09-21 | 2004-03-22 | Astrazeneca Ab | Quinazoline compounds and pharmaceutical compositions containing them |
WO2001032651A1 (en) | 1999-11-05 | 2001-05-10 | Astrazeneca Ab | Quinazoline derivatives as vegf inhibitors |
US7087613B2 (en) * | 1999-11-11 | 2006-08-08 | Osi Pharmaceuticals, Inc. | Treating abnormal cell growth with a stable polymorph of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine hydrochloride |
UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
DE60121931T2 (de) | 2000-04-07 | 2007-03-01 | Astrazeneca Ab | Chinazolinverbindungen |
US6653332B2 (en) | 2000-05-03 | 2003-11-25 | Tularik Inc. | Combination therapeutic compositions and method of use |
UA73993C2 (uk) | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
JP4044839B2 (ja) * | 2000-06-22 | 2008-02-06 | ファイザー・プロダクツ・インク | 異常細胞増殖を治療するための置換2環式誘導体 |
US20030171399A1 (en) | 2000-06-28 | 2003-09-11 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
CN1305872C (zh) * | 2000-06-30 | 2007-03-21 | 葛兰素集团有限公司 | 喹唑啉类化合物的制备方法 |
JP2004506732A (ja) | 2000-08-21 | 2004-03-04 | アストラゼネカ アクチボラグ | キナゾリン誘導体 |
US6849625B2 (en) * | 2000-10-13 | 2005-02-01 | Astrazeneca Ab | Quinazoline derivatives with anti-tumour activity |
AU2002217999A1 (en) * | 2000-11-01 | 2002-05-15 | Cor Therapeutics, Inc. | Process for the production of 4-quinazolinylpiperazin-1-carboxylic acid phenylamides |
US7102009B2 (en) | 2001-01-12 | 2006-09-05 | Amgen Inc. | Substituted amine derivatives and methods of use |
US7105682B2 (en) | 2001-01-12 | 2006-09-12 | Amgen Inc. | Substituted amine derivatives and methods of use |
JP2002293773A (ja) * | 2001-03-30 | 2002-10-09 | Sumika Fine Chemicals Co Ltd | キナゾリン誘導体の製造方法 |
US7132427B2 (en) | 2001-06-21 | 2006-11-07 | Ariad Pharmaceuticals, Inc. | Quinazolines and uses thereof |
NZ532524A (en) * | 2001-11-03 | 2007-02-23 | Astrazeneca Ab | Quinazoline derivatives as antitumor agents |
GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
DE60223279T2 (de) * | 2001-11-30 | 2008-05-29 | Osi Pharmaceuticals, Inc. | Verfahren für die herstellung substituierter bicyclischer derivate zur behandlung von anomalem zellwachstum |
DK1463506T3 (da) | 2001-12-24 | 2010-01-11 | Astrazeneca Ab | Substituerede quinazolin-derivater som inhibitorer af aurora-kinaser |
EP1471910A2 (en) | 2002-01-17 | 2004-11-03 | Neurogen Corporation | Substituted quinazolin-4-ylamine analogues as modulators of capsaicin receptors |
TWI324597B (en) * | 2002-03-28 | 2010-05-11 | Astrazeneca Ab | Quinazoline derivatives |
US6924285B2 (en) * | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
EP1521747B1 (en) | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
US7488823B2 (en) | 2003-11-10 | 2009-02-10 | Array Biopharma, Inc. | Cyanoguanidines and cyanoamidines as ErbB2 and EGFR inhibitors |
MY147761A (en) | 2002-12-24 | 2013-01-31 | Astrazeneca Ab | Chemical compounds |
WO2004069145A2 (en) * | 2003-02-07 | 2004-08-19 | Dr. Reddy's Laboratories Ltd. | Anticancer compounds, process for their preparation and pharmaceutical compositions containing them |
WO2004094410A1 (en) * | 2003-04-16 | 2004-11-04 | Astrazeneca Ab | Chemical compounds |
GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
GB0309850D0 (en) | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
BRPI0410720A (pt) * | 2003-05-27 | 2006-06-20 | Pfizer Prod Inc | quinazolinas e pirido[3,4-d]pirimidinas como inibidores do receptor de tirosina cinase |
WO2004105764A1 (en) * | 2003-06-02 | 2004-12-09 | Astrazeneca Ab | (3- ((quinazolin-4-yl) amino )-1h-pyrazol-1-yl) acetamide derivatives and related compounds as aurora kinase inhibitors for the treatment of proliferative diseases such as cancer |
EP1660479A1 (en) * | 2003-07-29 | 2006-05-31 | Astrazeneca AB | Piperidyl-quinazoline derivatives as tyrosine kinase inhibitors |
GB0317665D0 (en) | 2003-07-29 | 2003-09-03 | Astrazeneca Ab | Qinazoline derivatives |
DK1660090T3 (da) * | 2003-08-14 | 2012-12-17 | Array Biopharma Inc | Quinazolin-analoger som receptor-tyrosinkinase-inhibitorer |
US7501427B2 (en) | 2003-08-14 | 2009-03-10 | Array Biopharma, Inc. | Quinazoline analogs as receptor tyrosine kinase inhibitors |
PT1667992E (pt) * | 2003-09-19 | 2007-04-30 | Astrazeneca Ab | Derivados de quinazolina |
WO2005028470A1 (en) * | 2003-09-19 | 2005-03-31 | Astrazeneca Ab | Quinazoline derivatives |
CA2540008A1 (en) * | 2003-09-25 | 2005-04-07 | Astrazeneca Ab | Quinazoline derivatives |
SI2213661T1 (sl) | 2003-09-26 | 2011-11-30 | Exelixis Inc | c-Met modulatorji in postopki uporabe |
US7223761B2 (en) | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
WO2005048948A2 (en) | 2003-11-13 | 2005-06-02 | Ambit Biosciences Corporation | Urea derivatives as kinase modulators |
CN1890234A (zh) | 2003-12-23 | 2007-01-03 | 辉瑞大药厂 | 新颖的喹啉衍生物 |
WO2005070900A1 (en) * | 2004-01-22 | 2005-08-04 | Altana Pharma Ag | N-4-(6- (heteo) aryl-pyrimidin-4-ylaminophenyl) -bezenesulfonamides as kinase inhibitors |
US20070208023A1 (en) * | 2004-04-16 | 2007-09-06 | Smithkline Beecham Corporation | Cancer Treatment Method |
AU2005239878B9 (en) * | 2004-05-06 | 2010-01-07 | Warner-Lambert Company Llc | 4-phenylamino-quinazolin-6-yl-amides |
EP1763526B1 (en) * | 2004-06-28 | 2009-06-24 | Bayer Schering Pharma AG | 4,6-disubstituted pyrimidines and their use as protein kinase inhibitors |
KR20070084172A (ko) | 2004-10-12 | 2007-08-24 | 아스트라제네카 아베 | 퀴나졸린 유도체 |
US7947676B2 (en) | 2004-12-14 | 2011-05-24 | Astrazeneca Ab | Pyrazolo[3,4-d]pyrimidine compounds as antitumor agents |
ATE521603T1 (de) | 2005-02-26 | 2011-09-15 | Astrazeneca Ab | Chinazolinderivate als tyrosinkinaseinhibitoren |
JP2006347936A (ja) * | 2005-06-15 | 2006-12-28 | Bayer Cropscience Ag | 殺虫性ベンズアニリド類 |
ATE488513T1 (de) | 2005-09-20 | 2010-12-15 | Astrazeneca Ab | 4-(1h-indazol-5-ylamino)chinazolinverbindungen als inhibitoren der erbb-rezeptortyrosinkinase zur behandlung von krebs |
US8399666B2 (en) | 2005-11-04 | 2013-03-19 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
US7977359B2 (en) | 2005-11-04 | 2011-07-12 | Amira Pharmaceuticals, Inc. | 5-lipdxygenase-activating protein (FLAP) inhibitors |
GB2431927B (en) | 2005-11-04 | 2010-03-17 | Amira Pharmaceuticals Inc | 5-Lipoxygenase-activating protein (FLAP) inhibitors |
DE602006021645D1 (de) | 2005-11-15 | 2011-06-09 | Array Biopharma Inc | Verfahren und Zwischenverbindungen zur Herstellung von N4-Phenyl-Quinazolin-4-Amin Derivaten |
JP2009517450A (ja) | 2005-12-02 | 2009-04-30 | アストラゼネカ アクチボラグ | チロシンキナーゼ阻害薬としての4−アニリノ置換キナゾリン誘導体 |
CN101003514A (zh) | 2006-01-20 | 2007-07-25 | 上海艾力斯医药科技有限公司 | 喹唑啉衍生物、其制备方法及用途 |
UY30183A1 (es) * | 2006-03-02 | 2007-10-31 | Astrazeneca Ab | Derivados de quinolina |
EP1994024A2 (en) * | 2006-03-02 | 2008-11-26 | AstraZeneca AB | Quinoline derivatives |
US20070231298A1 (en) * | 2006-03-31 | 2007-10-04 | Cell Genesys, Inc. | Cytokine-expressing cancer immunotherapy combinations |
EP2022500A4 (en) | 2006-06-01 | 2010-11-24 | Jp Agency Of Nat Cancer Ct | TUMOR SUPPRESSOR |
EP1921070A1 (de) * | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
AU2008212999A1 (en) * | 2007-02-06 | 2008-08-14 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, drugs containing said compounds, use thereof, and method for production thereof |
UA101168C2 (ru) | 2007-10-29 | 2013-03-11 | Натко Фарма Лимитед | 4-(тетразол-5-ил)хиназолиновые производные как противораковые средства |
BRPI0907916A2 (pt) | 2008-02-07 | 2015-07-28 | Boehringer Ingelheim Int | Heterociclos espirociclos, medicamentos contendo esses compostos, e processos para preparar os mesmos |
CA2723989C (en) | 2008-05-13 | 2017-04-25 | Astrazeneca Ab | Fumarate salt of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(n-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline |
MX2010012814A (es) | 2008-05-23 | 2010-12-20 | Amira Pharmaceuticals Inc | Inhibidor de proteina activadora de 5-lipoxigenasa. |
EP2313397B1 (de) * | 2008-08-08 | 2016-04-20 | Boehringer Ingelheim International GmbH | Cyclohexyloxy-substituierte heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
US8546431B2 (en) | 2008-10-01 | 2013-10-01 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
EP2241565A1 (en) | 2009-01-15 | 2010-10-20 | Universität Leipzig | Aurora kinase inhibitors compounds |
TWI511956B (zh) | 2009-01-16 | 2015-12-11 | Exelixis Inc | 製備n-(4-{〔6,7-雙(甲氧基)喹啉-4-基〕氧基}苯基)-n’-(4-氟苯基)環丙烷-1,1-二甲醯胺之方法 |
UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
SI3351558T1 (sl) | 2009-11-13 | 2020-07-31 | Daiichi Sankyo Europe Gmbh | Material in postopki za zdravljenje ali preprečevanje bolezni, povezanih s HER-3 |
AU2011286407A1 (en) | 2010-08-06 | 2013-02-21 | Amgen | Use of HER3 binding agents in prostate treatment |
KR20130016041A (ko) * | 2011-08-04 | 2013-02-14 | 재단법인 의약바이오컨버젼스연구단 | 신규한 아닐린 유도체 및 이의 용도 |
CN102603496A (zh) * | 2011-09-26 | 2012-07-25 | 盘锦兴福化工有限公司 | 2,3—二氟苯丁醚的合成方法 |
ES2640648T3 (es) | 2013-09-16 | 2017-11-03 | Astrazeneca Ab | Nanopartículas poliméricas terapéuticas y métodos para su fabricación y uso |
UY36547A (es) | 2015-02-05 | 2016-06-01 | Bayer Cropscience Ag | Derivados heterocíclicos condensados bicíclicos sustituidos por 2-(het)arilo como pesticidas |
CA2981886A1 (en) | 2015-04-16 | 2016-10-20 | Icahn School Of Medicine At Mount Sinai | Ksr antagonists |
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Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1305095A (en) * | 1993-12-10 | 1995-06-27 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit csf-1r receptor tyrosine kinase |
Family Cites Families (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3266990A (en) * | 1963-09-24 | 1966-08-16 | Warner Lambert Pharmaceutical | Derivatives of quinazoline |
JPS5538325A (en) * | 1978-09-11 | 1980-03-17 | Sankyo Co Ltd | 4-anilinoquinazoline derivative and its preparation |
US4343940A (en) * | 1979-02-13 | 1982-08-10 | Mead Johnson & Company | Anti-tumor quinazoline compounds |
GB2160201B (en) * | 1984-06-14 | 1988-05-11 | Wyeth John & Brother Ltd | Quinazoline and cinnoline derivatives |
DE68917485T2 (de) * | 1988-01-23 | 1995-02-09 | Kyowa Hakko Kogyo Kk | Pyridazinon-Derivate und diese enthaltende pharmazeutische Zubereitungen. |
IL89029A (en) * | 1988-01-29 | 1993-01-31 | Lilly Co Eli | Fungicidal quinoline and cinnoline derivatives, compositions containing them, and fungicidal methods of using them |
CA2079113A1 (en) * | 1991-02-22 | 1992-08-23 | Calgene, Inc. | Seed plant fatty acyl reductase proteins and genes |
EP0584222B1 (en) * | 1991-05-10 | 1997-10-08 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
US5721237A (en) * | 1991-05-10 | 1998-02-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties |
NZ243082A (en) * | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
GB9300059D0 (en) * | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
US6177401B1 (en) * | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
GB9323290D0 (en) * | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
GB9314893D0 (en) * | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
GB9314884D0 (en) * | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Tricyclic derivatives |
CA2148082A1 (en) * | 1993-09-03 | 1995-03-09 | Daisuke Machii | Imidazoquinazoline derivatives |
GB9325217D0 (en) * | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
US5700823A (en) * | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
IL112249A (en) * | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
IL112248A0 (en) * | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
BR9506936A (pt) * | 1994-02-23 | 1997-09-09 | Pfizer | Derivados de quinazolina substituídos com 4-heterociclila processos para sua preparaçao e seu uso como agentes anticancerosos |
WO1995024190A2 (en) * | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
EP0682027B1 (de) * | 1994-05-03 | 1997-10-15 | Novartis AG | Pyrrolopyrimidinderivate mit antiproliferativer Wirkung |
TW414798B (en) * | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
GB9510757D0 (en) * | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
TW321649B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
GB9424233D0 (en) * | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
WO1996029331A1 (de) * | 1995-03-20 | 1996-09-26 | Dr. Karl Thomae Gmbh | Imidazochinazoline, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
WO1996030347A1 (en) * | 1995-03-30 | 1996-10-03 | Pfizer Inc. | Quinazoline derivatives |
CA2214086C (en) * | 1995-04-03 | 2008-07-29 | Novartis Ag | Pyrazole derivatives and processes for the preparation thereof |
GB9508538D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
GB9508535D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivative |
GB9508565D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
EP0824525B1 (en) * | 1995-04-27 | 2001-06-13 | AstraZeneca AB | Quinazoline derivatives |
GB9508537D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
IL117923A (en) * | 1995-05-03 | 2000-06-01 | Warner Lambert Co | Anti-cancer pharmaceutical compositions containing polysubstituted pyrido¬2,3-d¾pyrimidine derivatives and certain such novel compounds |
AU716993B2 (en) * | 1995-05-12 | 2000-03-16 | Neurogen Corporation | Novel deazapurine derivatives; a new class of CRF1 specific ligands |
PT831829E (pt) * | 1995-06-07 | 2003-12-31 | Pfizer | Derivados de pirimidina heterociclicos de aneis fundidos |
DE69618587T2 (de) * | 1995-06-07 | 2002-08-29 | Sugen, Inc. | Chinazoline und pharmazeutische zusammensetzungen |
DK0836605T3 (da) * | 1995-07-06 | 2002-05-13 | Novartis Ag | Pyrrolopyrimidiner og fremgangsmåder til deres fremstilling |
GB9514265D0 (en) * | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
AR004010A1 (es) * | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
GB9520822D0 (en) * | 1995-10-11 | 1995-12-13 | Wellcome Found | Therapeutically active compounds |
ES2159760T3 (es) * | 1995-11-14 | 2001-10-16 | Pharmacia & Upjohn Spa | Derivados de aril purina y piridopirimidina y de heteroaril purina y piridopirimidina. |
US5760041A (en) * | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
-
1995
- 1995-10-27 TW TW084111357A patent/TW321649B/zh not_active IP Right Cessation
- 1995-11-08 US US08/836,362 patent/US5821246A/en not_active Expired - Lifetime
- 1995-11-08 DE DE69507505T patent/DE69507505T2/de not_active Expired - Lifetime
- 1995-11-08 DK DK95936044T patent/DK0790986T3/da active
- 1995-11-08 JP JP51581696A patent/JP4011109B2/ja not_active Expired - Fee Related
- 1995-11-08 AU AU38130/95A patent/AU703328B2/en not_active Ceased
- 1995-11-08 NZ NZ294917A patent/NZ294917A/xx not_active IP Right Cessation
- 1995-11-08 WO PCT/GB1995/002606 patent/WO1996015118A1/en active IP Right Grant
- 1995-11-08 MX MX9702956A patent/MX9702956A/es unknown
- 1995-11-08 CA CA002200871A patent/CA2200871C/en not_active Expired - Fee Related
- 1995-11-08 ES ES95936044T patent/ES2128092T3/es not_active Expired - Lifetime
- 1995-11-08 EP EP95936044A patent/EP0790986B1/en not_active Expired - Lifetime
- 1995-11-08 AT AT95936044T patent/ATE175962T1/de active
- 1995-11-12 IL IL11595995A patent/IL115959A/en not_active IP Right Cessation
-
1997
- 1997-05-07 FI FI971970A patent/FI119933B/fi not_active IP Right Cessation
- 1997-05-09 NO NO972152A patent/NO307178B1/no not_active IP Right Cessation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1305095A (en) * | 1993-12-10 | 1995-06-27 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit csf-1r receptor tyrosine kinase |
Non-Patent Citations (1)
Title |
---|
INDIAN J. CHEM. VOL.19B, 1980, PP.1084-1087 * |
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CA2200871A1 (en) | 1996-05-23 |
CA2200871C (en) | 2008-08-19 |
FI971970A0 (fi) | 1997-05-07 |
MX9702956A (es) | 1997-06-28 |
NZ294917A (en) | 1999-02-25 |
EP0790986A1 (en) | 1997-08-27 |
FI971970A7 (fi) | 1997-05-07 |
ATE175962T1 (de) | 1999-02-15 |
DE69507505T2 (de) | 1999-06-02 |
FI119933B (fi) | 2009-05-15 |
WO1996015118A1 (en) | 1996-05-23 |
NO307178B1 (no) | 2000-02-21 |
TW321649B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1997-12-01 |
ES2128092T3 (es) | 1999-05-01 |
DK0790986T3 (da) | 1999-09-13 |
US5821246A (en) | 1998-10-13 |
NO972152D0 (no) | 1997-05-09 |
IL115959A (en) | 2004-06-20 |
JP4011109B2 (ja) | 2007-11-21 |
IL115959A0 (en) | 1996-01-31 |
JPH10508616A (ja) | 1998-08-25 |
DE69507505D1 (de) | 1999-03-04 |
AU3813095A (en) | 1996-06-06 |
NO972152L (no) | 1997-05-12 |
EP0790986B1 (en) | 1999-01-20 |
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