ES2523465T3 - Compuestos de quinazolina - Google Patents
Compuestos de quinazolina Download PDFInfo
- Publication number
- ES2523465T3 ES2523465T3 ES10828947.1T ES10828947T ES2523465T3 ES 2523465 T3 ES2523465 T3 ES 2523465T3 ES 10828947 T ES10828947 T ES 10828947T ES 2523465 T3 ES2523465 T3 ES 2523465T3
- Authority
- ES
- Spain
- Prior art keywords
- amino
- methyl
- methyloxy
- alkyl
- quinazolinyl
- 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 description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 269
- -1 amino, hydroxyl Chemical group 0.000 claims abstract description 256
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 92
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 60
- 150000002367 halogens Chemical class 0.000 claims abstract description 59
- 150000003839 salts Chemical class 0.000 claims abstract description 49
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 42
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 33
- 229910052717 sulfur Chemical group 0.000 claims abstract description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 29
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 26
- 125000005366 cycloalkylthio group Chemical group 0.000 claims abstract description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 24
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 20
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 18
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000001301 oxygen Chemical group 0.000 claims abstract description 15
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000011593 sulfur Chemical group 0.000 claims abstract description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 11
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
- 125000004995 haloalkylthio group Chemical group 0.000 claims abstract description 9
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 8
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 7
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims abstract description 6
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims abstract description 6
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 5
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims abstract description 4
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 183
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 61
- 206010019280 Heart failures Diseases 0.000 claims description 26
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 23
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 23
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 23
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 12
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 9
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 7
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 7
- 239000007983 Tris buffer Substances 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 6
- UIBXYETWZDSJHG-UHFFFAOYSA-N 3-[[7-(3-chloropropoxy)quinazolin-4-yl]amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC=C(OCCCCl)C=C3N=CN=2)=C1 UIBXYETWZDSJHG-UHFFFAOYSA-N 0.000 claims description 5
- 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 5
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 4
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- 125000006771 (C1-C6) haloalkylthio group Chemical group 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- TUINBAPNAKPWHO-UHFFFAOYSA-N 3-[[7-(3-methoxypropoxy)quinazolin-4-yl]amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC=C(OCCCOC)C=C3N=CN=2)=C1 TUINBAPNAKPWHO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- YUSROMRPOFFTMX-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 YUSROMRPOFFTMX-UHFFFAOYSA-N 0.000 claims description 3
- MVOYMLQGDVPZJA-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-[ethyl(methyl)amino]-n-methylbenzenesulfonamide Chemical compound CCN(C)C1=CC=C(S(=O)(=O)NC)C=C1NC1=NC=NC2=CC(OC)=C(OC)C=C12 MVOYMLQGDVPZJA-UHFFFAOYSA-N 0.000 claims description 3
- DUTAWJOHYORMCO-UHFFFAOYSA-N 3-[[7-(3-chloropropoxy)quinazolin-4-yl]amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=C(OCCCCl)C=C3N=CN=2)=C1 DUTAWJOHYORMCO-UHFFFAOYSA-N 0.000 claims description 3
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- RJSKVBNUBJSMHI-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-4-fluoro-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(F)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 RJSKVBNUBJSMHI-UHFFFAOYSA-N 0.000 claims description 2
- DNRQPIJNEGGAAA-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 DNRQPIJNEGGAAA-UHFFFAOYSA-N 0.000 claims description 2
- MACJBQSESOYMOK-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-(2,5-dimethylpyrrolidin-1-yl)-n-methylbenzenesulfonamide Chemical compound N=1C=NC2=CC(OC)=C(OC)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1C(C)CCC1C MACJBQSESOYMOK-UHFFFAOYSA-N 0.000 claims description 2
- HJWJQWGYZYLMGV-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 HJWJQWGYZYLMGV-UHFFFAOYSA-N 0.000 claims description 2
- VYSMSRYJJVHBRS-UHFFFAOYSA-N 3-[[6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC(OC)=C(OCCOC)C=C3N=CN=2)=C1 VYSMSRYJJVHBRS-UHFFFAOYSA-N 0.000 claims description 2
- DETZHDXVQPOGQN-UHFFFAOYSA-N 4-(4,4-difluoropiperidin-1-yl)-3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methylbenzenesulfonamide Chemical compound N=1C=NC2=CC(OC)=C(OC)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1CCC(F)(F)CC1 DETZHDXVQPOGQN-UHFFFAOYSA-N 0.000 claims description 2
- VSWVHOWZJGZKRL-UHFFFAOYSA-N 4-methoxy-3-[[7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC)C(NC=2C3=CC(OCCCN4CCOCC4)=C(OC)C=C3N=CN=2)=C1 VSWVHOWZJGZKRL-UHFFFAOYSA-N 0.000 claims description 2
- MRNDDGYEVRTLML-UHFFFAOYSA-N 5-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-(dimethylamino)-2-fluoro-n-methylbenzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)NC)=CC(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1N(C)C MRNDDGYEVRTLML-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- KFBXNJYHMZCVDH-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 KFBXNJYHMZCVDH-UHFFFAOYSA-N 0.000 claims 1
- LCFPGSGLOPXSJD-UHFFFAOYSA-N 5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2-fluoro-n-methylbenzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)NC)=CC(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 LCFPGSGLOPXSJD-UHFFFAOYSA-N 0.000 claims 1
- 125000005189 alkyl hydroxy group Chemical group 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract description 2
- 125000006648 (C1-C8) haloalkyl group Chemical group 0.000 abstract 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 224
- 238000005481 NMR spectroscopy Methods 0.000 description 137
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 91
- 239000000203 mixture Substances 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 239000007787 solid Substances 0.000 description 58
- 238000000034 method Methods 0.000 description 41
- 239000000243 solution Substances 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
- 235000019439 ethyl acetate Nutrition 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 26
- 238000002360 preparation method Methods 0.000 description 26
- 101000662993 Homo sapiens Serine/threonine-protein kinase TNNI3K Proteins 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 238000001914 filtration Methods 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 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
- 239000000284 extract Substances 0.000 description 18
- 102100037670 Serine/threonine-protein kinase TNNI3K Human genes 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- AWWJQWXSWOWSQP-UHFFFAOYSA-N 3-amino-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(N)=C1 AWWJQWXSWOWSQP-UHFFFAOYSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- LLLHRNQLGUOJHP-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 LLLHRNQLGUOJHP-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 15
- BTGIKZVZNHHDAU-UHFFFAOYSA-N 4-chloro-5,7-dimethoxyquinazoline Chemical compound ClC1=NC=NC2=CC(OC)=CC(OC)=C21 BTGIKZVZNHHDAU-UHFFFAOYSA-N 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- PRTLSVYSOPRSIX-UHFFFAOYSA-N 4-fluoro-n-methyl-3-nitrobenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(F)C([N+]([O-])=O)=C1 PRTLSVYSOPRSIX-UHFFFAOYSA-N 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 239000007832 Na2SO4 Substances 0.000 description 10
- 239000012298 atmosphere Substances 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- MUIRIRMDOFREES-UHFFFAOYSA-N 4-chloro-5,6,7-trimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C(OC)=C(OC)C(OC)=CC2=N1 MUIRIRMDOFREES-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- DKPBWQKQXNICDH-UHFFFAOYSA-N aniline;quinazoline Chemical compound NC1=CC=CC=C1.N1=CN=CC2=CC=CC=C21 DKPBWQKQXNICDH-UHFFFAOYSA-N 0.000 description 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 239000012453 solvate Substances 0.000 description 9
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 8
- 208000006029 Cardiomegaly Diseases 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 102000049185 human TNNI3K Human genes 0.000 description 7
- 150000004677 hydrates Chemical class 0.000 description 7
- 229960004592 isopropanol Drugs 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 229940124530 sulfonamide Drugs 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 description 6
- XJCQYMYLFKKZLX-UHFFFAOYSA-N 4-chloro-5-ethoxy-7-methoxyquinazoline Chemical compound C1=NC(Cl)=C2C(OCC)=CC(OC)=CC2=N1 XJCQYMYLFKKZLX-UHFFFAOYSA-N 0.000 description 6
- DGQAPUDRPYXACW-UHFFFAOYSA-N 5-amino-2-fluoro-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC(N)=C(OCC(F)(F)F)C=C1F DGQAPUDRPYXACW-UHFFFAOYSA-N 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 229930195733 hydrocarbon Natural products 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000007170 pathology Effects 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US257646P | 2000-12-22 | ||
| US25764609P | 2009-11-03 | 2009-11-03 | |
| PCT/US2010/054927 WO2011056740A1 (en) | 2009-11-03 | 2010-11-01 | Quinazoline compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2523465T3 true ES2523465T3 (es) | 2014-11-26 |
Family
ID=43970282
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10828947.1T Active ES2523465T3 (es) | 2009-11-03 | 2010-11-01 | Compuestos de quinazolina |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8859571B2 (enExample) |
| EP (1) | EP2501233B1 (enExample) |
| JP (1) | JP5836963B2 (enExample) |
| KR (1) | KR101736521B1 (enExample) |
| CN (1) | CN102711474B (enExample) |
| AU (1) | AU2010315361B2 (enExample) |
| BR (1) | BR112012010524A2 (enExample) |
| CA (1) | CA2779989A1 (enExample) |
| EA (1) | EA021439B1 (enExample) |
| ES (1) | ES2523465T3 (enExample) |
| IL (1) | IL219504A (enExample) |
| MX (1) | MX2012005155A (enExample) |
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| EP2398797B1 (en) * | 2009-02-17 | 2013-11-06 | Boehringer Ingelheim International GmbH | Pyrimido[5,4-d]pyrimidine derivatives for the inhibition of tyrosine kinases |
| CN103159685A (zh) * | 2013-04-11 | 2013-06-19 | 苏州立新制药有限公司 | 4-氯-6，7-二(2-甲氧基乙氧基)喹唑啉的制备方法 |
| AU2014353006B2 (en) * | 2013-11-20 | 2019-04-04 | Signalchem Life Sciences Corp. | Quinazoline derivatives as TAM family kinase inhibitors |
| WO2015099916A1 (en) | 2013-12-26 | 2015-07-02 | Exxonmobil Research And Engineering Company | Synthesis of zsm-48 crystals |
| KR20240017986A (ko) * | 2017-09-26 | 2024-02-08 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 암 치료를 위한 조성물 및 방법 |
| EP4031247A1 (en) | 2019-09-16 | 2022-07-27 | Novartis AG | Bifunctional degraders and their methods of use |
| CA3233057A1 (en) | 2021-09-23 | 2023-03-30 | Erasca, Inc. | Egfr inhibitor polymorph forms |
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| GB9508565D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
| EP2210607B1 (en) * | 2003-09-26 | 2011-08-17 | Exelixis Inc. | N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide for the treatment of cancer |
| WO2007053452A1 (en) | 2005-11-01 | 2007-05-10 | Targegen, Inc. | Bi-aryl meta-pyrimidine inhibitors of kinases |
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- 2010-11-01 CN CN201080060451.4A patent/CN102711474B/zh not_active Expired - Fee Related
- 2010-11-01 EP EP10828947.1A patent/EP2501233B1/en active Active
- 2010-11-01 EA EA201290243A patent/EA021439B1/ru not_active IP Right Cessation
- 2010-11-01 KR KR1020127014231A patent/KR101736521B1/ko not_active Expired - Fee Related
- 2010-11-01 CA CA2779989A patent/CA2779989A1/en not_active Abandoned
- 2010-11-01 AU AU2010315361A patent/AU2010315361B2/en not_active Ceased
- 2010-11-01 WO PCT/US2010/054927 patent/WO2011056740A1/en not_active Ceased
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- 2010-11-01 ES ES10828947.1T patent/ES2523465T3/es active Active
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2012
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Also Published As
| Publication number | Publication date |
|---|---|
| KR101736521B1 (ko) | 2017-05-16 |
| EA201290243A1 (ru) | 2012-12-28 |
| JP2013510155A (ja) | 2013-03-21 |
| IL219504A (en) | 2016-09-29 |
| CA2779989A1 (en) | 2011-05-12 |
| CN102711474B (zh) | 2014-09-10 |
| CN102711474A (zh) | 2012-10-03 |
| IL219504A0 (en) | 2012-06-28 |
| US8859571B2 (en) | 2014-10-14 |
| AU2010315361A1 (en) | 2012-05-24 |
| WO2011056740A1 (en) | 2011-05-12 |
| EP2501233A1 (en) | 2012-09-26 |
| JP5836963B2 (ja) | 2015-12-24 |
| EP2501233A4 (en) | 2013-06-19 |
| KR20120112441A (ko) | 2012-10-11 |
| MX2012005155A (es) | 2012-08-31 |
| EA021439B1 (ru) | 2015-06-30 |
| EP2501233B1 (en) | 2014-09-24 |
| AU2010315361B2 (en) | 2014-06-12 |
| BR112012010524A2 (pt) | 2017-12-12 |
| US20120220588A1 (en) | 2012-08-30 |
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