NO302233B1 - Nye, terapeutisk virksomme benzopyranderivater - Google Patents

Info

Publication number

NO302233B1

NO302233B1 NO923382A NO923382A NO302233B1 NO 302233 B1 NO302233 B1 NO 302233B1 NO 923382 A NO923382 A NO 923382A NO 923382 A NO923382 A NO 923382A NO 302233 B1 NO302233 B1 NO 302233B1

Authority

NO

Norway

Prior art keywords

formula

methyl

benzopyran

oxo

dihydropyridin

Prior art date

1991-08-29

Links

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• 150000001562 benzopyrans Chemical class 0.000 title claims description 13
• 150000001875 compounds Chemical class 0.000 claims description 401
• 239000001257 hydrogen Substances 0.000 claims description 154
• 229910052739 hydrogen Inorganic materials 0.000 claims description 154
• 125000000217 alkyl group Chemical group 0.000 claims description 105
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 85
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 80
• 150000003839 salts Chemical class 0.000 claims description 66
• 150000002431 hydrogen Chemical class 0.000 claims description 61
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 44
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
• 125000003545 alkoxy group Chemical group 0.000 claims description 25
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 19
• 229910052794 bromium Inorganic materials 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 19
• 150000002367 halogens Chemical class 0.000 claims description 19
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
• 125000001246 bromo group Chemical group Br* 0.000 claims description 15
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 13
• 231100000252 nontoxic Toxicity 0.000 claims description 9
• 230000003000 nontoxic effect Effects 0.000 claims description 9
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• FXRJKZVWFJSKGI-UHFFFAOYSA-N n-[[2,2-dimethyl-4-(2-oxopyridin-1-yl)-6-(trifluoromethyl)chromen-3-yl]methyl]-n-hydroxyacetamide Chemical compound C12=CC(C(F)(F)F)=CC=C2OC(C)(C)C(CN(O)C(=O)C)=C1N1C=CC=CC1=O FXRJKZVWFJSKGI-UHFFFAOYSA-N 0.000 claims description 8
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 8
• BSCZLAXSQNDWLZ-UHFFFAOYSA-N N-hydroxy-N-[2,2,5-trimethyl-6-nitro-4-(2-oxopyridin-1-yl)chromen-3-yl]acetamide Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=C(C(O2)(C)C)N(C(C)=O)O)N2C(C=CC=C2)=O)C=1C BSCZLAXSQNDWLZ-UHFFFAOYSA-N 0.000 claims description 7
• 239000000460 chlorine Substances 0.000 claims description 7
• 229910052801 chlorine Inorganic materials 0.000 claims description 7
• XITSSGJCHKTHNV-UHFFFAOYSA-N C(#N)C=1C=CC2=C(C(=C(C(O2)(C)C)N(C(C)=O)O)N2C(C=CC=C2)=O)C1C Chemical compound C(#N)C=1C=CC2=C(C(=C(C(O2)(C)C)N(C(C)=O)O)N2C(C=CC=C2)=O)C1C XITSSGJCHKTHNV-UHFFFAOYSA-N 0.000 claims description 6
• 239000000969 carrier Substances 0.000 claims description 6
• CXPLYZVAVAOCLJ-UHFFFAOYSA-N N-[2,2,5-trimethyl-6-nitro-4-(2-oxopyridin-1-yl)chromen-3-yl]acetamide Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=C(C(O2)(C)C)NC(C)=O)N2C(C=CC=C2)=O)C=1C CXPLYZVAVAOCLJ-UHFFFAOYSA-N 0.000 claims description 5
• YZVIXZYPIKNULR-UHFFFAOYSA-N N-[6-bromo-2,2,5-trimethyl-4-(2-oxopyridin-1-yl)chromen-3-yl]-N-hydroxyacetamide Chemical compound BrC=1C=CC2=C(C(=C(C(O2)(C)C)N(C(C)=O)O)N2C(C=CC=C2)=O)C=1C YZVIXZYPIKNULR-UHFFFAOYSA-N 0.000 claims description 5
• LMPQGZDAOUOFPE-UHFFFAOYSA-N n-[[2,2-dimethyl-6-nitro-4-(2-oxopyridin-1-yl)chromen-3-yl]methyl]formamide Chemical compound O=CNCC=1C(C)(C)OC2=CC=C([N+]([O-])=O)C=C2C=1N1C=CC=CC1=O LMPQGZDAOUOFPE-UHFFFAOYSA-N 0.000 claims description 5
• WRUWFSISNDFGPN-UHFFFAOYSA-N CC1(C)OC(C=CC(C(C(F)(F)F)(F)F)=C2C)=C2C(N(C=CC=C2)C2=O)=C1N(C(C)=O)O Chemical compound CC1(C)OC(C=CC(C(C(F)(F)F)(F)F)=C2C)=C2C(N(C=CC=C2)C2=O)=C1N(C(C)=O)O WRUWFSISNDFGPN-UHFFFAOYSA-N 0.000 claims description 4
• QBOMRUNRZJWUPL-UHFFFAOYSA-N CCC(=O)N(C1=C(C2=C(C=CC(=C2C)Br)OC1(C)C)N3C=CC=CC3=O)O Chemical compound CCC(=O)N(C1=C(C2=C(C=CC(=C2C)Br)OC1(C)C)N3C=CC=CC3=O)O QBOMRUNRZJWUPL-UHFFFAOYSA-N 0.000 claims description 4
• AKZUHNMDUXARND-UHFFFAOYSA-N N-[6-chloro-2,2,5-trimethyl-4-(2-oxopyridin-1-yl)chromen-3-yl]-N-hydroxyacetamide Chemical compound ClC=1C=CC2=C(C(=C(C(O2)(C)C)N(C(C)=O)O)N2C(C=CC=C2)=O)C=1C AKZUHNMDUXARND-UHFFFAOYSA-N 0.000 claims description 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• SBIGFTCRXXKNLK-UHFFFAOYSA-N 1-[3-(hydroxyamino)-2,2,5-trimethyl-6-nitrochromen-4-yl]pyridin-2-one Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=C(C(O2)(C)C)NO)N2C(C=CC=C2)=O)C=1C SBIGFTCRXXKNLK-UHFFFAOYSA-N 0.000 claims description 3
• MMIAOQJHUALFSF-UHFFFAOYSA-N 1-[3-(methoxyamino)-2,2,5-trimethyl-6-nitrochromen-4-yl]pyridin-2-one Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=C(C(O2)(C)C)NOC)N2C(C=CC=C2)=O)C=1C MMIAOQJHUALFSF-UHFFFAOYSA-N 0.000 claims description 3
• OYDMTNATKBXKTJ-UHFFFAOYSA-N 2,2,2-trifluoro-n-[2,2,5-trimethyl-4-(2-oxopyridin-1-yl)-6-(trifluoromethyl)chromen-3-yl]acetamide Chemical compound FC(F)(F)C(=O)NC=1C(C)(C)OC2=CC=C(C(F)(F)F)C(C)=C2C=1N1C=CC=CC1=O OYDMTNATKBXKTJ-UHFFFAOYSA-N 0.000 claims description 3
• CGFKICGGTDRWGT-UHFFFAOYSA-N N-[2,2,5-trimethyl-4-(2-oxopyridin-1-yl)-6-(trifluoromethyl)chromen-3-yl]formamide Chemical compound FC(C=1C=CC2=C(C(=C(C(O2)(C)C)NC=O)N2C(C=CC=C2)=O)C=1C)(F)F CGFKICGGTDRWGT-UHFFFAOYSA-N 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 3
• IASZFMFGJXHDKR-UHFFFAOYSA-N n-[[2,2-dimethyl-6-nitro-4-(2-oxopyridin-1-yl)chromen-3-yl]methyl]-2,2,2-trifluoroacetamide Chemical compound FC(F)(F)C(=O)NCC=1C(C)(C)OC2=CC=C([N+]([O-])=O)C=C2C=1N1C=CC=CC1=O IASZFMFGJXHDKR-UHFFFAOYSA-N 0.000 claims description 2
• ALRMNUBOFIIHKG-UHFFFAOYSA-N N-[2,2,5-trimethyl-4-(2-oxopyridin-1-yl)-6-(trifluoromethyl)chromen-3-yl]acetamide Chemical compound FC(C=1C=CC2=C(C(=C(C(O2)(C)C)NC(C)=O)N2C(C=CC=C2)=O)C=1C)(F)F ALRMNUBOFIIHKG-UHFFFAOYSA-N 0.000 claims 1
• 150000001721 carbon Chemical group 0.000 claims 1
• 125000005843 halogen group Chemical group 0.000 claims 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
• 238000002360 preparation method Methods 0.000 description 190
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 120
• 238000006243 chemical reaction Methods 0.000 description 99
• 239000000243 solution Substances 0.000 description 73
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
• -1 n-octyl Chemical group 0.000 description 57
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
• 238000000034 method Methods 0.000 description 48
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
• 239000000203 mixture Substances 0.000 description 39
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 36
• 238000007796 conventional method Methods 0.000 description 30
• 238000002844 melting Methods 0.000 description 29
• 230000008018 melting Effects 0.000 description 29
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
• 201000010099 disease Diseases 0.000 description 26
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• 230000002829 reductive effect Effects 0.000 description 24
• 239000002904 solvent Substances 0.000 description 23
• 239000012442 inert solvent Substances 0.000 description 22
• 238000004519 manufacturing process Methods 0.000 description 22
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• 239000003921 oil Substances 0.000 description 18
• 235000019198 oils Nutrition 0.000 description 18
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
• 241001465754 Metazoa Species 0.000 description 16
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• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• 239000000047 product Substances 0.000 description 15
• 239000000741 silica gel Substances 0.000 description 15
• 229910002027 silica gel Inorganic materials 0.000 description 15
• 238000012360 testing method Methods 0.000 description 15
• 150000001412 amines Chemical class 0.000 description 13
• 238000002474 experimental method Methods 0.000 description 13
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 12
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• 238000004587 chromatography analysis Methods 0.000 description 12
• 238000002425 crystallisation Methods 0.000 description 12
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• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
• IFRZEKXFKUQQTL-UHFFFAOYSA-N 1-[3-(aminomethyl)-2,2-dimethyl-6-nitrochromen-4-yl]pyridin-2-one Chemical compound NCC=1C(C)(C)OC2=CC=C([N+]([O-])=O)C=C2C=1N1C=CC=CC1=O IFRZEKXFKUQQTL-UHFFFAOYSA-N 0.000 description 10
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• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 9
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