JP4285996B2 - キナゾリン誘導体 - Google Patents
キナゾリン誘導体 Download PDFInfo
- Publication number
- JP4285996B2 JP4285996B2 JP2002565961A JP2002565961A JP4285996B2 JP 4285996 B2 JP4285996 B2 JP 4285996B2 JP 2002565961 A JP2002565961 A JP 2002565961A JP 2002565961 A JP2002565961 A JP 2002565961A JP 4285996 B2 JP4285996 B2 JP 4285996B2
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- JP
- Japan
- Prior art keywords
- group
- hydrogen atom
- alkyl
- alkyl group
- alkoxy
- 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.)
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- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 163
- 239000000203 mixture Substances 0.000 claims abstract description 126
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 23
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 22
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 22
- 239000012453 solvate Substances 0.000 claims abstract description 20
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 18
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 105
- 239000013078 crystal Substances 0.000 claims description 101
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 43
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 125000005843 halogen group Chemical group 0.000 claims description 32
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000003277 amino group Chemical group 0.000 claims description 22
- 102000001301 EGF receptor Human genes 0.000 claims description 17
- 108060006698 EGF receptor Proteins 0.000 claims description 17
- 201000011510 cancer Diseases 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 11
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 11
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 10
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 230000000069 prophylactic effect Effects 0.000 claims description 8
- 239000013543 active substance Substances 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 239000003112 inhibitor Substances 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 238000010521 absorption reaction Methods 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 229940043355 kinase inhibitor Drugs 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 239000003909 protein kinase inhibitor Substances 0.000 claims description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 29
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 9
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims 6
- 150000004677 hydrates Chemical class 0.000 claims 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 3
- 125000002947 alkylene group Chemical group 0.000 claims 2
- 125000002993 cycloalkylene group Chemical group 0.000 claims 2
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 13
- 201000004681 Psoriasis Diseases 0.000 abstract description 6
- 206010003210 Arteriosclerosis Diseases 0.000 abstract description 5
- 208000011775 arteriosclerosis disease Diseases 0.000 abstract description 5
- 238000011282 treatment Methods 0.000 abstract description 4
- 239000008177 pharmaceutical agent Substances 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 216
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 136
- 239000000243 solution Substances 0.000 description 108
- 238000005481 NMR spectroscopy Methods 0.000 description 99
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 87
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 84
- 230000002829 reductive effect Effects 0.000 description 80
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 76
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 74
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 70
- 238000001914 filtration Methods 0.000 description 68
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 67
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 66
- 238000000034 method Methods 0.000 description 64
- 238000003756 stirring Methods 0.000 description 62
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 61
- 230000015572 biosynthetic process Effects 0.000 description 58
- 238000003786 synthesis reaction Methods 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000002904 solvent Substances 0.000 description 54
- -1 amino Chemical group 0.000 description 53
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
- 238000005160 1H NMR spectroscopy Methods 0.000 description 45
- 238000006243 chemical reaction Methods 0.000 description 42
- 239000007787 solid Substances 0.000 description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 35
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 32
- 239000000047 product Substances 0.000 description 32
- 239000002244 precipitate Substances 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 22
- 239000000706 filtrate Substances 0.000 description 22
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 235000019441 ethanol Nutrition 0.000 description 20
- 238000010898 silica gel chromatography Methods 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- VWWMOACCGFHMEV-UHFFFAOYSA-N dicarbide(2-) Chemical compound [C-]#[C-] VWWMOACCGFHMEV-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 238000001816 cooling Methods 0.000 description 17
- 238000002441 X-ray diffraction Methods 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 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 16
- 239000003814 drug Substances 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 229940079593 drug Drugs 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 239000012043 crude product Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 150000003246 quinazolines Chemical class 0.000 description 11
- 229910052727 yttrium Inorganic materials 0.000 description 11
- 0 CCC*(CCC#Cc1cc2ncnc(*)c2cc1N)CI Chemical compound CCC*(CCC#Cc1cc2ncnc(*)c2cc1N)CI 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000012046 mixed solvent Substances 0.000 description 10
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- VESUQRNXJYOTRH-UHFFFAOYSA-N 7-bromo-4-n-(3-chloro-4-fluorophenyl)quinazoline-4,6-diamine Chemical compound N1=CN=C2C=C(Br)C(N)=CC2=C1NC1=CC=C(F)C(Cl)=C1 VESUQRNXJYOTRH-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- 239000004215 Carbon black (E152) Substances 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 230000008878 coupling Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- 229930195733 hydrocarbon Natural products 0.000 description 8
- 150000002430 hydrocarbons Chemical class 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 7
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 7
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 7
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- 239000002798 polar solvent Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 6
- UQHYVHRBGYMGHE-UHFFFAOYSA-N 1-(2-methylbut-3-yn-2-yl)piperazine Chemical compound C#CC(C)(C)N1CCNCC1 UQHYVHRBGYMGHE-UHFFFAOYSA-N 0.000 description 6
- FNFHQDOUVJYCMH-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-7-[3-methyl-3-(4-methylpiperazin-1-yl)but-1-ynyl]quinazoline-4,6-diamine Chemical compound C1CN(C)CCN1C(C)(C)C#CC1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=C1N FNFHQDOUVJYCMH-UHFFFAOYSA-N 0.000 description 6
- JJJKJGYBIXGWMM-UHFFFAOYSA-N 7-bromo-n-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine Chemical compound N1=CN=C2C=C(Br)C([N+](=O)[O-])=CC2=C1NC1=CC=C(F)C(Cl)=C1 JJJKJGYBIXGWMM-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- 150000002828 nitro derivatives Chemical class 0.000 description 6
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
- 239000003586 protic polar solvent Substances 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 5
- YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 5
- FUGKKMYSCAYXJJ-UHFFFAOYSA-N 7-bromo-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C=2C1=CC(Br)=CC=2 FUGKKMYSCAYXJJ-UHFFFAOYSA-N 0.000 description 5
- JNMLGRZESMSECU-UHFFFAOYSA-N 7-bromo-n-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=C(Br)C([N+](=O)[O-])=CC2=C1NC1=CC=C(F)C(Cl)=C1 JNMLGRZESMSECU-UHFFFAOYSA-N 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- JTNFIHUVAZVCFP-UHFFFAOYSA-N [7-ethoxy-4-[3-(3-hydroxy-3-methylbut-1-ynyl)anilino]quinazolin-6-yl] trifluoromethanesulfonate Chemical compound C=12C=C(OS(=O)(=O)C(F)(F)F)C(OCC)=CC2=NC=NC=1NC1=CC=CC(C#CC(C)(C)O)=C1 JTNFIHUVAZVCFP-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 5
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 5
- 239000003701 inert diluent Substances 0.000 description 5
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Images
Classifications
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- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- 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
- C07D239/94—Nitrogen atoms
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- 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
- C07D405/06—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 carbon chain containing only aliphatic carbon atoms
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Cardiology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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JP2001045827 | 2001-02-21 | ||
JP2001045827 | 2001-02-21 | ||
JP2001353525 | 2001-11-19 | ||
JP2001353525 | 2001-11-19 | ||
PCT/JP2002/001575 WO2002066445A1 (fr) | 2001-02-21 | 2002-02-21 | Derives de la quinazoline |
Publications (3)
Publication Number | Publication Date |
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JPWO2002066445A6 JPWO2002066445A6 (ja) | 2004-06-17 |
JPWO2002066445A1 JPWO2002066445A1 (ja) | 2004-06-17 |
JP4285996B2 true JP4285996B2 (ja) | 2009-06-24 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014518544A (ja) * | 2011-03-04 | 2014-07-31 | ニューゲン セラピューティクス, インコーポレイテッド | アルキン置換キナゾリン化合物および使用方法 |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW200813014A (en) | 2002-03-28 | 2008-03-16 | 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 |
GB0309850D0 (en) | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
HRP20080329T3 (en) | 2003-09-16 | 2008-08-31 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
PT1667992E (pt) * | 2003-09-19 | 2007-04-30 | Astrazeneca Ab | Derivados de quinazolina |
DE602004004811T2 (de) * | 2003-09-19 | 2007-11-22 | Astrazeneca Ab | Chinazolinderivate |
JP2007506716A (ja) * | 2003-09-25 | 2007-03-22 | アストラゼネカ アクチボラグ | キナゾリン誘導体 |
GB0322409D0 (en) | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
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EP1690856A4 (en) * | 2003-11-28 | 2007-09-05 | Aveo Pharmaceuticals Inc | CHINAZOLINE DERIVATIVE AND METHOD FOR THE PRODUCTION THEREOF |
WO2005075439A1 (en) | 2004-02-03 | 2005-08-18 | Astrazeneca Ab | Quinazoline derivatives |
RS52119B (en) | 2004-05-06 | 2012-08-31 | Warner-Lambert Company Llc | 4-phenylamino-HINAZOLIN-6-IL-STARCHES |
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CN101124228B (zh) | 2004-12-14 | 2011-06-15 | 阿斯利康(瑞典)有限公司 | 用作抗肿瘤药物的吡唑并嘧啶化合物 |
US8202879B2 (en) | 2005-02-23 | 2012-06-19 | Shionogi & Co., Ltd. | Quinazoline derivatives having tyrosine kinase inhibitory activity |
MX2007010399A (es) | 2005-02-26 | 2007-09-25 | Astrazeneca Ab | Derivados de quinazolina en la forma de inhibidores de cinasa de tirosina. |
WO2006106721A1 (ja) * | 2005-03-30 | 2006-10-12 | Shionogi & Co., Ltd. | チロシンキナーゼ阻害作用を有するピリミジン誘導体 |
JP2009508918A (ja) | 2005-09-20 | 2009-03-05 | アストラゼネカ アクチボラグ | 癌治療のためのerbB受容体チロシンキナーゼ阻害剤としての4−(1H−インダゾール−5−イル]アミノ)キナゾリン化合物 |
EP2010183A4 (en) * | 2006-03-03 | 2010-08-25 | Aveo Pharmaceuticals Inc | PROCESS FOR SYNTHESIS OF 7-ALKINYL-4-AMINOCHINAZOLINES AND A RELATED INTERMEDIATE COMPOUND |
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CA2677336A1 (en) | 2007-02-06 | 2008-08-14 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, the use thereof and processes for the preparation thereof |
DK2245026T3 (da) | 2008-02-07 | 2012-10-15 | Boehringer Ingelheim Int | Spirocycliske heterocycler, lægemiddel indeholdende disse forbindelser, deres anvendelse og fremgangsmåde til deres fremstilling |
EA019183B1 (ru) * | 2008-05-13 | 2014-01-30 | Астразенека Аб | Фумаратная соль 4-(3-хлор-2-фторанилино)-7-метокси-6-{[1-(n-метилкарбамоилметил)пиперидин-4-ил]окси}хиназолина |
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 |
MX2012010557A (es) * | 2010-03-16 | 2012-10-05 | Merck Patent Gmbh | Morfolinilquinazolinas. |
CN102918029B (zh) * | 2011-05-17 | 2015-06-17 | 江苏康缘药业股份有限公司 | 4-苯胺-6-丁烯酰胺-7-烷醚喹唑啉衍生物及其制备方法和用途 |
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US9464089B2 (en) | 2012-01-13 | 2016-10-11 | Acea Biosciences Inc. | Heterocyclic compounds and uses thereof |
CA2861010A1 (en) | 2012-01-13 | 2013-07-18 | Xiao Xu | Heterocyclic compounds and uses as anticancer agents |
CN103254143B (zh) * | 2013-04-26 | 2015-10-07 | 浙江工业大学 | 4-[4-(2-二乙氨基乙酰氨基)苯胺基]-6-取代喹唑啉类化合物及制备和应用 |
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CN105916851A (zh) | 2013-07-11 | 2016-08-31 | 艾森生物科学公司 | 嘧啶衍生物作为激酶抑制剂 |
AU2016334141B2 (en) | 2015-10-09 | 2019-12-19 | ACEA Therapeutics, Inc. | Pharmaceutical salts, physical forms, and compositions of pyrrolopyrimidine kinase inhibitors, and methods of making same |
CN110430881A (zh) * | 2017-01-30 | 2019-11-08 | 盐野义制药株式会社 | 含有喹唑啉衍生物的固体制剂 |
CN111212837A (zh) | 2017-04-07 | 2020-05-29 | 艾森医药公司 | 吡咯并嘧啶激酶抑制剂的药用盐、物理形态和组合物及其制备方法 |
WO2019233459A1 (zh) * | 2018-06-08 | 2019-12-12 | 江苏威凯尔医药科技有限公司 | 人表皮生长因子受体抑制剂及其制备方法和应用 |
CN110577514B (zh) * | 2018-06-08 | 2022-07-05 | 江苏威凯尔医药科技有限公司 | 人表皮生长因子受体抑制剂及其制备方法和应用 |
US20220298120A1 (en) * | 2019-08-15 | 2022-09-22 | Black Diamond Therapeutics, Inc. | Alkynyl quinazoline compounds |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3134236B2 (ja) | 1992-01-30 | 2001-02-13 | 株式会社林原生物化学研究所 | α−グリコシル−L−アスコルビン酸高含有物の製造方法とその製造のための分離システム |
JP2994165B2 (ja) | 1992-06-26 | 1999-12-27 | ゼネカ・リミテッド | キナゾリン誘導体、その製造法および該キナゾリン誘導体を含有する抗癌作用を得るための医薬調剤 |
GEP20012442B (en) | 1996-04-12 | 2001-05-25 | Warner Lambert Co | Irreversible Inhibitors of Tyrosine Kinases |
EP0837063A1 (en) * | 1996-10-17 | 1998-04-22 | Pfizer Inc. | 4-Aminoquinazoline derivatives |
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 |
UA73990C2 (en) * | 2000-06-22 | 2005-10-17 | Pfizer Prod Inc | Substituted bicyclic derivatives for the treatment of abnormal cells growth |
EP1690856A4 (en) * | 2003-11-28 | 2007-09-05 | Aveo Pharmaceuticals Inc | CHINAZOLINE DERIVATIVE AND METHOD FOR THE PRODUCTION THEREOF |
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- 2002-02-21 TW TW091102988A patent/TWI309647B/zh active
- 2002-02-21 JP JP2002565961A patent/JP4285996B2/ja not_active Expired - Fee Related
- 2002-02-21 DE DE60237145T patent/DE60237145D1/de not_active Expired - Lifetime
- 2002-02-21 US US10/468,788 patent/US7294629B2/en not_active Expired - Fee Related
- 2002-02-21 CN CNB028052609A patent/CN1264824C/zh not_active Expired - Fee Related
- 2002-02-21 KR KR1020037011020A patent/KR100861486B1/ko not_active Expired - Fee Related
- 2002-02-21 AT AT02700688T patent/ATE475652T1/de not_active IP Right Cessation
- 2002-02-21 WO PCT/JP2002/001575 patent/WO2002066445A1/ja active Application Filing
- 2002-02-21 EP EP02700688A patent/EP1369418B1/en not_active Expired - Lifetime
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014518544A (ja) * | 2011-03-04 | 2014-07-31 | ニューゲン セラピューティクス, インコーポレイテッド | アルキン置換キナゾリン化合物および使用方法 |
US11524956B2 (en) | 2011-03-04 | 2022-12-13 | Newgen Therapeutics, Inc. | Alkyne substituted quinazoline compound and methods of use |
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CA2442742A1 (en) | 2002-08-29 |
EP1369418A4 (en) | 2005-09-14 |
TWI309647B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2009-05-11 |
US20040116422A1 (en) | 2004-06-17 |
KR100861486B1 (ko) | 2008-10-02 |
EP1369418A1 (en) | 2003-12-10 |
US7294629B2 (en) | 2007-11-13 |
DE60237145D1 (de) | 2010-09-09 |
EP1369418B1 (en) | 2010-07-28 |
CN1264824C (zh) | 2006-07-19 |
US20070265260A1 (en) | 2007-11-15 |
ATE475652T1 (de) | 2010-08-15 |
KR20030086269A (ko) | 2003-11-07 |
JPWO2002066445A1 (ja) | 2004-06-17 |
WO2002066445A1 (fr) | 2002-08-29 |
CN1492860A (zh) | 2004-04-28 |
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