JP2005516955A - アロイル・ピリジノン化合物 - Google Patents
アロイル・ピリジノン化合物 Download PDFInfo
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- JP2005516955A JP2005516955A JP2003554683A JP2003554683A JP2005516955A JP 2005516955 A JP2005516955 A JP 2005516955A JP 2003554683 A JP2003554683 A JP 2003554683A JP 2003554683 A JP2003554683 A JP 2003554683A JP 2005516955 A JP2005516955 A JP 2005516955A
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- Prior art keywords
- alkoxy
- substituted
- alkyl
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- -1 Aroyl pyridinone compounds Chemical class 0.000 title claims description 56
- 238000000034 method Methods 0.000 claims abstract description 32
- 239000003814 drug Substances 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 124
- 239000000203 mixture Substances 0.000 claims description 88
- 125000001424 substituent group Chemical group 0.000 claims description 74
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 64
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 33
- 235000019260 propionic acid Nutrition 0.000 claims description 32
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 32
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- 239000000460 chlorine Chemical group 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 11
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 11
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 230000008578 acute process Effects 0.000 claims description 6
- 230000006020 chronic inflammation Effects 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 150000001412 amines Chemical group 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000006091 1,3-dioxolane group Chemical group 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
- XOTUAMWIFRDGMZ-UHFFFAOYSA-N 2-chloroprop-2-enoyl chloride Chemical compound ClC(=C)C(Cl)=O XOTUAMWIFRDGMZ-UHFFFAOYSA-N 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- YYFIGOPUHPDIBO-UHFFFAOYSA-N propanoic acid;hydrochloride Chemical compound Cl.CCC(O)=O YYFIGOPUHPDIBO-UHFFFAOYSA-N 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- YTLYLLTVENPWFT-UPHRSURJSA-N (Z)-3-aminoacrylic acid Chemical compound N\C=C/C(O)=O YTLYLLTVENPWFT-UPHRSURJSA-N 0.000 claims 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 239000012752 auxiliary agent Substances 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 7
- 150000005299 pyridinones Chemical class 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 122
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 111
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 67
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
- 230000002829 reductive effect Effects 0.000 description 64
- 238000005160 1H NMR spectroscopy Methods 0.000 description 63
- 238000010992 reflux Methods 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 239000003480 eluent Substances 0.000 description 36
- 239000000243 solution Substances 0.000 description 35
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 32
- 235000019341 magnesium sulphate Nutrition 0.000 description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- 239000012074 organic phase Substances 0.000 description 28
- 239000002244 precipitate Substances 0.000 description 26
- 238000002953 preparative HPLC Methods 0.000 description 25
- 239000012141 concentrate Substances 0.000 description 23
- 235000008504 concentrate Nutrition 0.000 description 23
- 238000001816 cooling Methods 0.000 description 22
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 21
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 21
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 21
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 21
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 150000003839 salts Chemical class 0.000 description 11
- SSJXIUAHEKJCMH-OLQVQODUSA-N (1s,2r)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-OLQVQODUSA-N 0.000 description 10
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 9
- 108090001007 Interleukin-8 Proteins 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 229910052796 boron Inorganic materials 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 210000000440 neutrophil Anatomy 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- WSHCMRXFHOORNG-UHFFFAOYSA-N 1-(4-fluorophenyl)-3,3-bis(methylsulfanyl)prop-2-en-1-one Chemical compound CSC(SC)=CC(=O)C1=CC=C(F)C=C1 WSHCMRXFHOORNG-UHFFFAOYSA-N 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 206010040070 Septic Shock Diseases 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- NJVAMOASFIGCQS-UHFFFAOYSA-N ethanol;2-methylpentane Chemical compound CCO.CCCC(C)C NJVAMOASFIGCQS-UHFFFAOYSA-N 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- GPYHXBMRTUGLQA-UHFFFAOYSA-N 1-(4-chlorophenyl)-3,3-bis(methylsulfanyl)prop-2-en-1-one Chemical compound CSC(SC)=CC(=O)C1=CC=C(Cl)C=C1 GPYHXBMRTUGLQA-UHFFFAOYSA-N 0.000 description 4
- BKRQPGGEQSTJFK-UHFFFAOYSA-N 3,3-bis(methylsulfanyl)-1-phenylprop-2-en-1-one Chemical compound CSC(SC)=CC(=O)C1=CC=CC=C1 BKRQPGGEQSTJFK-UHFFFAOYSA-N 0.000 description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 210000000424 bronchial epithelial cell Anatomy 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 3
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 3
- DDHUNHGZUHZNKB-UHFFFAOYSA-N 2,2-dimethylpropane-1,3-diamine Chemical compound NCC(C)(C)CN DDHUNHGZUHZNKB-UHFFFAOYSA-N 0.000 description 3
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- 239000012089 stop solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000000825 ultraviolet detection Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- SKRZCMLCDIDIFT-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3,3-bis(methylsulfanyl)prop-2-en-1-one Chemical compound CSC(SC)=CC(=O)C1=CC=C(F)C=C1F SKRZCMLCDIDIFT-UHFFFAOYSA-N 0.000 description 2
- MNKQALXLMAXQAL-UHFFFAOYSA-N 1-(2-chlorophenyl)-3,3-bis(methylsulfanyl)prop-2-en-1-one Chemical compound CSC(SC)=CC(=O)C1=CC=CC=C1Cl MNKQALXLMAXQAL-UHFFFAOYSA-N 0.000 description 2
- NAJBKHJRXPYTCV-UHFFFAOYSA-N 1-(2-methylphenyl)-3,3-bis(methylsulfanyl)prop-2-en-1-one Chemical compound CSC(SC)=CC(=O)C1=CC=CC=C1C NAJBKHJRXPYTCV-UHFFFAOYSA-N 0.000 description 2
- HGBLSWGFGWUCAD-UHFFFAOYSA-N 1-(3-bromophenyl)-3,3-bis(methylsulfanyl)prop-2-en-1-one Chemical compound CSC(SC)=CC(=O)C1=CC=CC(Br)=C1 HGBLSWGFGWUCAD-UHFFFAOYSA-N 0.000 description 2
- SOLPFAMKJGMEQF-UHFFFAOYSA-N 1-(3-chlorophenyl)-3,3-bis(methylsulfanyl)prop-2-en-1-one Chemical compound CSC(SC)=CC(=O)C1=CC=CC(Cl)=C1 SOLPFAMKJGMEQF-UHFFFAOYSA-N 0.000 description 2
- CGGPQWFRUOOXFA-UHFFFAOYSA-N 1-(3-fluorophenyl)-3,3-bis(methylsulfanyl)prop-2-en-1-one Chemical compound CSC(SC)=CC(=O)C1=CC=CC(F)=C1 CGGPQWFRUOOXFA-UHFFFAOYSA-N 0.000 description 2
- OGDXGQXGWXTOCU-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(5,5-dimethyl-1,3-diazinan-2-ylidene)ethanone Chemical compound N1CC(C)(C)CNC1=CC(=O)C1=CC=C(Cl)C=C1 OGDXGQXGWXTOCU-UHFFFAOYSA-N 0.000 description 2
- TWVHWTDMYDDLEH-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-(5-hydroxy-1,3-diazinan-2-ylidene)ethanone Chemical compound N1CC(O)CNC1=CC(=O)C1=CC=C(F)C=C1 TWVHWTDMYDDLEH-UHFFFAOYSA-N 0.000 description 2
- AWNXKZVIZARMME-UHFFFAOYSA-N 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol Chemical compound N=1C(NCC(C)(O)C)=NC=C(C=2N=C(NC=3C=C(Cl)N=CC=3)N=CC=2)C=1CC1CC1 AWNXKZVIZARMME-UHFFFAOYSA-N 0.000 description 2
- 125000006334 2,4-difluoro benzoyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(F)C([H])=C1F 0.000 description 2
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/22—Radicals substituted by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/12—Radicals substituted by oxygen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0130723A GB2387170A (en) | 2001-12-21 | 2001-12-21 | Antiinflammatory pyridinones |
| GBGB0131102.6A GB0131102D0 (en) | 2001-12-21 | 2001-12-31 | Aroyl pyridinones |
| GB0210511A GB0210511D0 (en) | 2002-05-08 | 2002-05-08 | Aroyl pyridinones |
| PCT/EP2002/013930 WO2003053967A1 (en) | 2001-12-21 | 2002-12-09 | Aroyl pyridinones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005516955A true JP2005516955A (ja) | 2005-06-09 |
| JP2005516955A5 JP2005516955A5 (https=) | 2006-02-02 |
Family
ID=27256362
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003554683A Pending JP2005516955A (ja) | 2001-12-21 | 2002-12-09 | アロイル・ピリジノン化合物 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20050070555A1 (https=) |
| EP (1) | EP1458717B1 (https=) |
| JP (1) | JP2005516955A (https=) |
| AU (1) | AU2002366730A1 (https=) |
| CA (1) | CA2471085A1 (https=) |
| DE (1) | DE60206072T2 (https=) |
| ES (1) | ES2250750T3 (https=) |
| WO (1) | WO2003053967A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007217322A (ja) * | 2006-02-15 | 2007-08-30 | Ube Ind Ltd | 慢性閉塞性肺疾患の治療又は予防のための医薬組成物 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1736475A1 (en) * | 2005-06-21 | 2006-12-27 | Ferrer Internacional, S.A. | Halogenated pyrazolo[1,5-a]pyrimidines, processes, uses, compositions and intermediates |
| BRPI1006150A2 (pt) | 2009-01-13 | 2018-01-16 | Interquim Sa | Processo para preparação de n-[5-(3-dimetilamino- acriloil)-2fluorofenil]-n-metil-acetamida |
| US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2358891A1 (fr) * | 1976-07-22 | 1978-02-17 | Yamanouchi Pharma Co Ltd | Composes heterocycliques contenant un azote, utilise comme agents analgesiques et anti-inflammatoires |
| EP0948496A2 (en) * | 1996-12-05 | 1999-10-13 | Amgen inc. | Substituted pyrimidinone and pyridone compounds and methods of use |
-
2002
- 2002-12-09 EP EP02805310A patent/EP1458717B1/en not_active Expired - Lifetime
- 2002-12-09 WO PCT/EP2002/013930 patent/WO2003053967A1/en not_active Ceased
- 2002-12-09 JP JP2003554683A patent/JP2005516955A/ja active Pending
- 2002-12-09 CA CA002471085A patent/CA2471085A1/en not_active Abandoned
- 2002-12-09 US US10/498,870 patent/US20050070555A1/en not_active Abandoned
- 2002-12-09 DE DE60206072T patent/DE60206072T2/de not_active Expired - Fee Related
- 2002-12-09 ES ES02805310T patent/ES2250750T3/es not_active Expired - Lifetime
- 2002-12-09 AU AU2002366730A patent/AU2002366730A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007217322A (ja) * | 2006-02-15 | 2007-08-30 | Ube Ind Ltd | 慢性閉塞性肺疾患の治療又は予防のための医薬組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| DE60206072T2 (de) | 2006-07-13 |
| WO2003053967A1 (en) | 2003-07-03 |
| DE60206072D1 (en) | 2005-10-13 |
| ES2250750T3 (es) | 2006-04-16 |
| EP1458717B1 (en) | 2005-09-07 |
| US20050070555A1 (en) | 2005-03-31 |
| CA2471085A1 (en) | 2003-07-03 |
| EP1458717A1 (en) | 2004-09-22 |
| AU2002366730A1 (en) | 2003-07-09 |
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