EA021439B1 - Хиназолиновые соединения - Google Patents

Info

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

2009-11-03

Links

• Espacenet
• Global Dossier
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• 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
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 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
• 229930195733 hydrocarbon Natural products 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
• 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
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• 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 5
• 108091000080 Phosphotransferase Proteins 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 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
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
• 102000020233 phosphotransferase Human genes 0.000 description 5
• 125000004076 pyridyl group Chemical group 0.000 description 5
• 150000003246 quinazolines Chemical class 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 229940032147 starch Drugs 0.000 description 5
• 235000019698 starch Nutrition 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 4
• BWYJJZBRYSADRP-UHFFFAOYSA-N 2-methoxyquinazoline Chemical compound C1=CC=CC2=NC(OC)=NC=C21 BWYJJZBRYSADRP-UHFFFAOYSA-N 0.000 description 4
• 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
• 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 description 4
• 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 0.000 description 4
• 150000001350 alkyl halides Chemical class 0.000 description 4
• DKPBWQKQXNICDH-UHFFFAOYSA-N aniline;quinazoline Chemical compound NC1=CC=CC=C1.N1=CN=CC2=CC=CC=C21 DKPBWQKQXNICDH-UHFFFAOYSA-N 0.000 description 4
• 150000001448 anilines Chemical class 0.000 description 4
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• 238000000605 extraction Methods 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 238000002875 fluorescence polarization Methods 0.000 description 4
• 239000012458 free base Substances 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 229910052740 iodine Inorganic materials 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• 239000012044 organic layer Substances 0.000 description 4
• 238000007911 parenteral administration Methods 0.000 description 4
• 239000011541 reaction mixture Substances 0.000 description 4
• 238000004007 reversed phase HPLC Methods 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• DEVUYWTZRXOMSI-UHFFFAOYSA-N (sulfamoylamino)benzene Chemical compound NS(=O)(=O)NC1=CC=CC=C1 DEVUYWTZRXOMSI-UHFFFAOYSA-N 0.000 description 3
• XAZYVFJSHFBTTM-UHFFFAOYSA-N 2,4-difluoro-5-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC(S(Cl)(=O)=O)=C(F)C=C1F XAZYVFJSHFBTTM-UHFFFAOYSA-N 0.000 description 3
• XJBHIZXBVPGRHH-UHFFFAOYSA-N 2-fluoro-5-nitro-4-(2,2,2-trifluoroethoxy)benzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC(S(Cl)(=O)=O)=C(F)C=C1OCC(F)(F)F XJBHIZXBVPGRHH-UHFFFAOYSA-N 0.000 description 3
• VQHGELUKJYOETQ-UHFFFAOYSA-N 2-fluoro-5-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(F)C(S(Cl)(=O)=O)=C1 VQHGELUKJYOETQ-UHFFFAOYSA-N 0.000 description 3
• LHKYXFQCFKOOCS-UHFFFAOYSA-N 2-methyl-3-nitrobenzenesulfonamide Chemical compound CC1=C([N+]([O-])=O)C=CC=C1S(N)(=O)=O LHKYXFQCFKOOCS-UHFFFAOYSA-N 0.000 description 3
• XZLYLEIECXYKNJ-UHFFFAOYSA-N 4,5,6-trimethoxy-1h-indole-2,3-dione Chemical compound COC1=C(OC)C(OC)=CC2=C1C(=O)C(=O)N2 XZLYLEIECXYKNJ-UHFFFAOYSA-N 0.000 description 3
• JUDHRKDDXFHONV-UHFFFAOYSA-N 4,5-dichloro-6,7-dimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C(Cl)=C(OC)C(OC)=CC2=N1 JUDHRKDDXFHONV-UHFFFAOYSA-N 0.000 description 3
• JEBCOVKUVLFOGR-UHFFFAOYSA-N 4,6-dichloroquinazoline Chemical compound N1=CN=C(Cl)C2=CC(Cl)=CC=C21 JEBCOVKUVLFOGR-UHFFFAOYSA-N 0.000 description 3
• DEETUTHTBFVLAH-UHFFFAOYSA-N 4-chloro-6-ethoxy-7-methoxyquinazoline Chemical compound N1=CN=C2C=C(OC)C(OCC)=CC2=C1Cl DEETUTHTBFVLAH-UHFFFAOYSA-N 0.000 description 3
• USOVRXNIZFSGEU-UHFFFAOYSA-N 4-fluoro-1-nitro-2-(2,2,2-trifluoroethoxy)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1OCC(F)(F)F USOVRXNIZFSGEU-UHFFFAOYSA-N 0.000 description 3
• RRONENSZKCGROA-UHFFFAOYSA-N 4-fluoro-3-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC(S(Cl)(=O)=O)=CC=C1F RRONENSZKCGROA-UHFFFAOYSA-N 0.000 description 3
• JLFAHVDBMXMNLK-UHFFFAOYSA-N 5,6,7-trimethoxy-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=C1C=C(OC)C(OC)=C2OC JLFAHVDBMXMNLK-UHFFFAOYSA-N 0.000 description 3
• LWFCXCUIINZJIQ-UHFFFAOYSA-N 5-ethoxy-7-methoxy-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=C1C=C(OC)C=C2OCC LWFCXCUIINZJIQ-UHFFFAOYSA-N 0.000 description 3
• GQBCDMUMKMBTME-UHFFFAOYSA-N 6-amino-2,3,4-trimethoxybenzoic acid Chemical compound COC1=CC(N)=C(C(O)=O)C(OC)=C1OC GQBCDMUMKMBTME-UHFFFAOYSA-N 0.000 description 3
• LWYYBCHNCHYKFF-UHFFFAOYSA-N 6-ethoxy-7-methoxy-1h-quinazolin-4-one Chemical compound N1=CN=C2C=C(OC)C(OCC)=CC2=C1O LWYYBCHNCHYKFF-UHFFFAOYSA-N 0.000 description 3
• 239000005541 ACE inhibitor Substances 0.000 description 3
• 229940123338 Aldosterone synthase inhibitor Drugs 0.000 description 3
• 229940127291 Calcium channel antagonist Drugs 0.000 description 3
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