EA021439B1 - Хиназолиновые соединения - Google Patents
Хиназолиновые соединения Download PDFInfo
- Publication number
- EA021439B1 EA021439B1 EA201290243A EA201290243A EA021439B1 EA 021439 B1 EA021439 B1 EA 021439B1 EA 201290243 A EA201290243 A EA 201290243A EA 201290243 A EA201290243 A EA 201290243A EA 021439 B1 EA021439 B1 EA 021439B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- amino
- methyloxy
- methyl
- quinazolinyl
- benzenesulfonamide
- Prior art date
Links
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 238000000034 method Methods 0.000 claims abstract description 52
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 285
- -1 nitro, amino Chemical group 0.000 claims description 247
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 209
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 66
- 229910052736 halogen Inorganic materials 0.000 claims description 59
- 150000002367 halogens Chemical class 0.000 claims description 59
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
- 125000005842 heteroatom Chemical group 0.000 claims description 29
- 206010019280 Heart failures Diseases 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 229910052717 sulfur Chemical group 0.000 claims description 16
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 15
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 14
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 14
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 14
- IGZRIDWPBSHEJD-UHFFFAOYSA-N n-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound FC(F)(F)CONS(=O)(=O)C1=CC=CC=C1 IGZRIDWPBSHEJD-UHFFFAOYSA-N 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
- 239000011593 sulfur Chemical group 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 239000007983 Tris buffer Substances 0.000 claims description 9
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 8
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 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 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 7
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 7
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 7
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 6
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 6
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 6
- 125000006771 (C1-C6) haloalkylthio group Chemical group 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
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 5
- SYSZAPOYYCUNDC-UHFFFAOYSA-N N-(1,1,1-trifluoropropan-2-yloxy)benzenesulfonamide Chemical compound FC(F)(F)C(C)ONS(=O)(=O)C1=CC=CC=C1 SYSZAPOYYCUNDC-UHFFFAOYSA-N 0.000 claims description 5
- 239000013256 coordination polymer Substances 0.000 claims description 5
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 229940124530 sulfonamide Drugs 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000004209 (C1-C8) alkyl 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
- UAGKWEYNDATOBQ-UHFFFAOYSA-N N'-methyl-N'-(2,2,2-trifluoroethyl)benzenesulfonohydrazide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NN(CC(F)(F)F)C UAGKWEYNDATOBQ-UHFFFAOYSA-N 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 claims description 2
- 102100036859 Troponin I, cardiac muscle Human genes 0.000 claims description 2
- 101710128251 Troponin I, cardiac muscle Proteins 0.000 claims description 2
- 125000005968 oxazolinyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 4
- MSFQEZBRFPAFEX-UHFFFAOYSA-N 4-methoxybenzenesulfonamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1 MSFQEZBRFPAFEX-UHFFFAOYSA-N 0.000 claims 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 2
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims 2
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims 1
- 125000005936 piperidyl group Chemical group 0.000 claims 1
- 125000002755 pyrazolinyl group Chemical group 0.000 claims 1
- 125000002769 thiazolinyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 64
- 239000007787 solid Substances 0.000 description 57
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- 238000004519 manufacturing process Methods 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000001914 filtration Methods 0.000 description 20
- 238000011282 treatment Methods 0.000 description 20
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 17
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 15
- 239000000460 chlorine Substances 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 230000000694 effects Effects 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 11
- 239000012267 brine Substances 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- BTGIKZVZNHHDAU-UHFFFAOYSA-N 4-chloro-5,7-dimethoxyquinazoline Chemical compound ClC1=NC=NC2=CC(OC)=CC(OC)=C21 BTGIKZVZNHHDAU-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000012453 solvate Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 208000006029 Cardiomegaly Diseases 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 150000004677 hydrates Chemical class 0.000 description 7
- 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
- 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 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 230000006870 function Effects 0.000 description 6
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
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- 108091000080 Phosphotransferase Proteins 0.000 description 5
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- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 5
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- CLXWMMGXFSZUNP-UHFFFAOYSA-N 2-methyl-5-nitrobenzenesulfonamide Chemical compound CC1=CC=C([N+]([O-])=O)C=C1S(N)(=O)=O CLXWMMGXFSZUNP-UHFFFAOYSA-N 0.000 description 4
- CLATWDTWMVIPHK-UHFFFAOYSA-N 5-[2-[[3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzoyl]amino]ethylcarbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid Chemical compound CC1=CC=C(O)C=C1NC1=CC=NC(NC=2C=C(C=CC=2)C(=O)NCCNC(=O)C=2C=C(C(=CC=2)C2=C3C=CC(=O)C=C3OC3=CC(O)=CC=C32)C(O)=O)=N1 CLATWDTWMVIPHK-UHFFFAOYSA-N 0.000 description 4
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- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 210000002235 sarcomere Anatomy 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940023144 sodium glycolate Drugs 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000005881 triazolinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25764609P | 2009-11-03 | 2009-11-03 | |
| PCT/US2010/054927 WO2011056740A1 (en) | 2009-11-03 | 2010-11-01 | Quinazoline compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201290243A1 EA201290243A1 (ru) | 2012-12-28 |
| EA021439B1 true EA021439B1 (ru) | 2015-06-30 |
Family
ID=43970282
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201290243A EA021439B1 (ru) | 2009-11-03 | 2010-11-01 | Хиназолиновые соединения |
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) |
| WO (1) | WO2011056740A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6015814A (en) * | 1995-04-27 | 2000-01-18 | Zeneca Limited | Quinazoline derivative |
| US20070259904A1 (en) * | 2005-11-01 | 2007-11-08 | Targegen, Inc. | Bi-aryl meta-pyrimidine inhibitors of kinases |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
2010
- 2010-11-01 MX MX2012005155A patent/MX2012005155A/es active IP Right Grant
- 2010-11-01 US US13/505,324 patent/US8859571B2/en not_active Expired - Fee Related
- 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
- 2010-11-01 JP JP2012537925A patent/JP5836963B2/ja not_active Expired - Fee Related
- 2010-11-01 BR BR112012010524A patent/BR112012010524A2/pt not_active IP Right Cessation
- 2010-11-01 ES ES10828947.1T patent/ES2523465T3/es active Active
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2012
- 2012-04-30 IL IL219504A patent/IL219504A/en not_active IP Right Cessation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6015814A (en) * | 1995-04-27 | 2000-01-18 | Zeneca Limited | Quinazoline derivative |
| US20070259904A1 (en) * | 2005-11-01 | 2007-11-08 | Targegen, Inc. | Bi-aryl meta-pyrimidine inhibitors of kinases |
Also Published As
| Publication number | Publication date |
|---|---|
| KR101736521B1 (ko) | 2017-05-16 |
| ES2523465T3 (es) | 2014-11-26 |
| 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 |
| EP2501233B1 (en) | 2014-09-24 |
| AU2010315361B2 (en) | 2014-06-12 |
| BR112012010524A2 (pt) | 2017-12-12 |
| US20120220588A1 (en) | 2012-08-30 |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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