CA2453860A1 - Imidazopyridinones as p38 map kinase inhibitors - Google Patents
Imidazopyridinones as p38 map kinase inhibitors Download PDFInfo
- Publication number
- CA2453860A1 CA2453860A1 CA002453860A CA2453860A CA2453860A1 CA 2453860 A1 CA2453860 A1 CA 2453860A1 CA 002453860 A CA002453860 A CA 002453860A CA 2453860 A CA2453860 A CA 2453860A CA 2453860 A1 CA2453860 A1 CA 2453860A1
- Authority
- CA
- Canada
- Prior art keywords
- mmol
- alkyl
- benzimidazol
- methyl
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- JXXWJMUPNZDILL-UHFFFAOYSA-N imidazo[4,5-b]pyridin-2-one Chemical class C1=CC=NC2=NC(=O)N=C21 JXXWJMUPNZDILL-UHFFFAOYSA-N 0.000 title abstract description 3
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 title description 14
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 title description 14
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 71
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 230000008569 process Effects 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 175
- 239000000203 mixture Substances 0.000 claims description 49
- 239000001257 hydrogen Substances 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- -1 C5-C8-heteroaryl Chemical group 0.000 claims description 27
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical group 0.000 claims description 24
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 20
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 19
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 230000008578 acute process Effects 0.000 claims description 6
- 230000006020 chronic inflammation Effects 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 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 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 abstract description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 164
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 163
- 238000005160 1H NMR spectroscopy Methods 0.000 description 112
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 106
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- 239000000243 solution Substances 0.000 description 51
- 239000002904 solvent Substances 0.000 description 50
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 47
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 43
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 description 36
- 239000003480 eluent Substances 0.000 description 30
- 229940093499 ethyl acetate Drugs 0.000 description 23
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- XMLUAPAWXDNVTM-UHFFFAOYSA-N 2-methyl-4,5,6,7-tetrahydro-1h-benzimidazole Chemical compound C1CCCC2=C1N=C(C)N2 XMLUAPAWXDNVTM-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 238000002953 preparative HPLC Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- 101150041968 CDC13 gene Proteins 0.000 description 12
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 229960004132 diethyl ether Drugs 0.000 description 10
- 150000002431 hydrogen Chemical class 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- JSWRVDNTKPAJLB-UHFFFAOYSA-N 2,4-difluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C(F)=C1 JSWRVDNTKPAJLB-UHFFFAOYSA-N 0.000 description 9
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 150000001728 carbonyl compounds Chemical class 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- PTBPTNCGZUOCBK-UHFFFAOYSA-N 2,4,5-trimethyl-1h-imidazole Chemical compound CC1=NC(C)=C(C)N1 PTBPTNCGZUOCBK-UHFFFAOYSA-N 0.000 description 8
- 108090001007 Interleukin-8 Proteins 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 210000000440 neutrophil Anatomy 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- GDKAPGMGFDSKQG-UHFFFAOYSA-N 2,4-dimethyl-4,5,6,7-tetrahydro-1h-benzimidazole Chemical compound CC1CCCC2=C1N=C(C)N2 GDKAPGMGFDSKQG-UHFFFAOYSA-N 0.000 description 6
- QNWYGEBYJATBJJ-UHFFFAOYSA-N 2-(4,5-dimethyl-1h-imidazol-2-yl)-1-(3-methylphenyl)ethanone;hydrochloride Chemical compound Cl.N1C(C)=C(C)N=C1CC(=O)C1=CC=CC(C)=C1 QNWYGEBYJATBJJ-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 229910052796 boron Inorganic materials 0.000 description 6
- 235000011167 hydrochloric acid Nutrition 0.000 description 6
- 229960000443 hydrochloric acid Drugs 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- CKRGGAAMDXILOQ-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-2-(4-ethyl-5-methyl-1h-imidazol-2-yl)ethanone Chemical compound N1C(C)=C(CC)N=C1CC(=O)C1=CC=C(F)C=C1F CKRGGAAMDXILOQ-UHFFFAOYSA-N 0.000 description 5
- LCDHMOLSRJZVKM-UHFFFAOYSA-N 2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)-1-thiophen-2-ylethanone Chemical compound N=1C=2CCCCC=2NC=1CC(=O)C1=CC=CS1 LCDHMOLSRJZVKM-UHFFFAOYSA-N 0.000 description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 5
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- NJVAMOASFIGCQS-UHFFFAOYSA-N ethanol;2-methylpentane Chemical compound CCO.CCCC(C)C NJVAMOASFIGCQS-UHFFFAOYSA-N 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- AFDZIDKANNEZMF-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound FC1=CC(F)=CC=C1C(=O)CC(N1)=NC2=C1CCCC2 AFDZIDKANNEZMF-UHFFFAOYSA-N 0.000 description 4
- RHOFJYFQSXZPMM-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-2-(4,6-dimethyl-4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound N1C=2CC(C)CC(C)C=2N=C1CC(=O)C1=CC=C(F)C=C1F RHOFJYFQSXZPMM-UHFFFAOYSA-N 0.000 description 4
- JCELKMHHPBJCID-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-(5-propan-2-yl-1h-imidazol-2-yl)ethanone Chemical compound CC(C)C1=CNC(CC(=O)C=2C=CC(F)=CC=2)=N1 JCELKMHHPBJCID-UHFFFAOYSA-N 0.000 description 4
- XVJCRCJCZVPWKX-UHFFFAOYSA-N 2-(4-butyl-5-methyl-1h-imidazol-2-yl)-1-(2,4-difluorophenyl)ethanone Chemical compound N1C(C)=C(CCCC)N=C1CC(=O)C1=CC=C(F)C=C1F XVJCRCJCZVPWKX-UHFFFAOYSA-N 0.000 description 4
- VPAYBEFRBJALDR-UHFFFAOYSA-N 2-(5,6-dimethyl-4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)-1-(4-fluorophenyl)ethanone Chemical compound N1C=2CC(C)C(C)CC=2N=C1CC(=O)C1=CC=C(F)C=C1 VPAYBEFRBJALDR-UHFFFAOYSA-N 0.000 description 4
- DUSACWROZJGKFP-UHFFFAOYSA-N 2-(5-bromo-1h-imidazol-2-yl)-1-(4-fluorophenyl)ethanone Chemical compound C1=CC(F)=CC=C1C(=O)CC1=NC(Br)=CN1 DUSACWROZJGKFP-UHFFFAOYSA-N 0.000 description 4
- KOYPPBGLOZEUAX-UHFFFAOYSA-N 2-(5-methyl-4-propyl-1h-imidazol-2-yl)-1-phenylethanone;hydrochloride Chemical compound Cl.N1C(C)=C(CCC)N=C1CC(=O)C1=CC=CC=C1 KOYPPBGLOZEUAX-UHFFFAOYSA-N 0.000 description 4
- 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 4
- NELFWLUXURRZAY-UHFFFAOYSA-N 4-ethyl-2,5-dimethyl-1h-imidazole Chemical compound CCC=1N=C(C)NC=1C NELFWLUXURRZAY-UHFFFAOYSA-N 0.000 description 4
- APLZLUYWLINBOZ-UHFFFAOYSA-N 5-bromo-2-methyl-1h-imidazole Chemical compound CC1=NC=C(Br)N1 APLZLUYWLINBOZ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 210000000424 bronchial epithelial cell Anatomy 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 230000002757 inflammatory effect Effects 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
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- 210000002741 palatine tonsil Anatomy 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- RDBHHKNTDIHCKA-UHFFFAOYSA-N (5-chloroimidazo[1,2-a]pyridin-8-yl)-phenylmethanone Chemical compound C12=NC=CN2C(Cl)=CC=C1C(=O)C1=CC=CC=C1 RDBHHKNTDIHCKA-UHFFFAOYSA-N 0.000 description 3
- NEINKHPCTDXXMB-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-2-(4-methyl-4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound N=1C=2C(C)CCCC=2NC=1CC(=O)C1=CC=C(F)C=C1F NEINKHPCTDXXMB-UHFFFAOYSA-N 0.000 description 3
- OADHYGIHERZQHN-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-2-(5,6-dimethyl-4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound N1C=2CC(C)C(C)CC=2N=C1CC(=O)C1=CC=C(F)C=C1F OADHYGIHERZQHN-UHFFFAOYSA-N 0.000 description 3
- MLDCNKAHKLLCFR-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-2-(6-methyl-4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound N=1C=2CC(C)CCC=2NC=1CC(=O)C1=CC=C(F)C=C1F MLDCNKAHKLLCFR-UHFFFAOYSA-N 0.000 description 3
- FTXUDPDUAKATRA-UHFFFAOYSA-N 1-(2,5-difluorophenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound FC1=CC=C(F)C(C(=O)CC=2NC=3CCCCC=3N=2)=C1 FTXUDPDUAKATRA-UHFFFAOYSA-N 0.000 description 3
- UOXYTMAFAIGYBV-UHFFFAOYSA-N 1-(2-chlorophenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound ClC1=CC=CC=C1C(=O)CC(N1)=NC2=C1CCCC2 UOXYTMAFAIGYBV-UHFFFAOYSA-N 0.000 description 3
- IAVVZJDLVYQGDH-UHFFFAOYSA-N 1-(2-methylphenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound CC1=CC=CC=C1C(=O)CC(N1)=NC2=C1CCCC2 IAVVZJDLVYQGDH-UHFFFAOYSA-N 0.000 description 3
- CSKAINKGRNKFQV-UHFFFAOYSA-N 1-(3,4-difluorophenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound C1=C(F)C(F)=CC=C1C(=O)CC(N1)=NC2=C1CCCC2 CSKAINKGRNKFQV-UHFFFAOYSA-N 0.000 description 3
- JMKSBWASCFZGON-UHFFFAOYSA-N 1-(3-bromophenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound BrC1=CC=CC(C(=O)CC=2NC=3CCCCC=3N=2)=C1 JMKSBWASCFZGON-UHFFFAOYSA-N 0.000 description 3
- DLMJULNQTWXYBD-UHFFFAOYSA-N 1-(3-chlorophenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound ClC1=CC=CC(C(=O)CC=2NC=3CCCCC=3N=2)=C1 DLMJULNQTWXYBD-UHFFFAOYSA-N 0.000 description 3
- SPDLTRSBYYXGMJ-UHFFFAOYSA-N 1-(3-chlorophenyl)-2-(4,5-dimethyl-1h-imidazol-2-yl)ethanone;hydrochloride Chemical compound Cl.N1C(C)=C(C)N=C1CC(=O)C1=CC=CC(Cl)=C1 SPDLTRSBYYXGMJ-UHFFFAOYSA-N 0.000 description 3
- WNISPHKJHHJTBT-UHFFFAOYSA-N 1-(4-bromophenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound C1=CC(Br)=CC=C1C(=O)CC(N1)=NC2=C1CCCC2 WNISPHKJHHJTBT-UHFFFAOYSA-N 0.000 description 3
- CUQUVOSQYXCXKQ-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-(4-methyl-4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone;hydrochloride Chemical compound Cl.N=1C=2C(C)CCCC=2NC=1CC(=O)C1=CC=C(F)C=C1 CUQUVOSQYXCXKQ-UHFFFAOYSA-N 0.000 description 3
- VHRZMEGNGIQQKX-UHFFFAOYSA-N 1-(4-methoxyphenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone Chemical compound C1=CC(OC)=CC=C1C(=O)CC(N1)=NC2=C1CCCC2 VHRZMEGNGIQQKX-UHFFFAOYSA-N 0.000 description 3
- PMFIHZYDEQQJDP-UHFFFAOYSA-N 1-(4-methylphenyl)-2-(4,5,6,7-tetrahydro-1h-benzimidazol-2-yl)ethanone;hydrochloride Chemical compound Cl.C1=CC(C)=CC=C1C(=O)CC(N1)=NC2=C1CCCC2 PMFIHZYDEQQJDP-UHFFFAOYSA-N 0.000 description 3
- OCAFZLRTMGCSSI-UHFFFAOYSA-N 2,4,6-trimethyl-1h-benzimidazole Chemical compound CC1=CC(C)=C2NC(C)=NC2=C1 OCAFZLRTMGCSSI-UHFFFAOYSA-N 0.000 description 3
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- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0117506.6A GB0117506D0 (en) | 2001-07-18 | 2001-07-18 | Imidazopyridinones |
| GB0117506.6 | 2001-07-18 | ||
| PCT/EP2002/007834 WO2003008413A1 (en) | 2001-07-18 | 2002-07-15 | Imidazopyridinones as p38 map kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2453860A1 true CA2453860A1 (en) | 2003-01-30 |
Family
ID=9918733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002453860A Abandoned CA2453860A1 (en) | 2001-07-18 | 2002-07-15 | Imidazopyridinones as p38 map kinase inhibitors |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6984646B2 (enExample) |
| EP (1) | EP1412353B1 (enExample) |
| JP (1) | JP2005502636A (enExample) |
| CA (1) | CA2453860A1 (enExample) |
| DE (1) | DE60203120T2 (enExample) |
| ES (1) | ES2238592T3 (enExample) |
| GB (1) | GB0117506D0 (enExample) |
| WO (1) | WO2003008413A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60331367D1 (de) | 2002-12-30 | 2010-04-01 | Angiotech Int Ag | Wirkstofffreisetzung von schnell gelierender polymerzusammensetzung |
| DE10341533A1 (de) * | 2003-09-09 | 2005-03-31 | Bayer Chemicals Ag | Verfahren zur Herstellung von halogenhaltigen 4-Aminophenolen |
| US7504403B2 (en) | 2004-01-22 | 2009-03-17 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| WO2005103288A1 (ja) * | 2004-04-27 | 2005-11-03 | Takeda Pharmaceutical Company Limited | スクリーニング方法 |
| 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 |
| ES2301380B1 (es) | 2006-08-09 | 2009-06-08 | Laboratorios Almirall S.A. | Nuevos derivados de 1,7-naftiridina. |
| ES2320955B1 (es) | 2007-03-02 | 2010-03-16 | Laboratorios Almirall S.A. | Nuevos derivados de 3-((1,2,4)triazolo(4,3-a)piridin-7-il)benzamida. |
| ES2329639B1 (es) | 2007-04-26 | 2010-09-23 | Laboratorios Almirall S.A. | Nuevos derivados de 4,8-difenilpoliazanaftaleno. |
| EP2108641A1 (en) | 2008-04-11 | 2009-10-14 | Laboratorios Almirall, S.A. | New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors |
| EP2113503A1 (en) | 2008-04-28 | 2009-11-04 | Laboratorios Almirall, S.A. | New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors |
| EP2322176A1 (en) | 2009-11-11 | 2011-05-18 | Almirall, S.A. | New 7-phenyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives |
| CN103910682B (zh) * | 2013-11-28 | 2016-03-02 | 大连理工大学 | 一种基于邻苯二胺环化的苯并咪唑类化合物制备方法 |
| JP2015209502A (ja) * | 2014-04-25 | 2015-11-24 | 株式会社Adeka | 硬化剤、およびこれを用いた硬化性樹脂組成物 |
| KR20170005868A (ko) | 2014-05-23 | 2017-01-16 | 액티브 바이오테크 에이비 | S100-저해제로서 유용한 새로운 화합물 |
| WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
| CN108727345B (zh) * | 2017-04-25 | 2023-06-27 | 广东东阳光药业有限公司 | 一种咪唑环中间体的制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5585595A (en) * | 1978-12-25 | 1980-06-27 | Yamanouchi Pharmaceut Co Ltd | Novel heterocyclic compound |
| DE2908364A1 (de) * | 1979-03-03 | 1980-09-11 | Hoechst Ag | Neue optische aufheller und fluoreszenzfarbstoffe sowie verfahren zu deren herstellung |
-
2001
- 2001-07-18 GB GBGB0117506.6A patent/GB0117506D0/en not_active Ceased
-
2002
- 2002-07-15 DE DE60203120T patent/DE60203120T2/de not_active Expired - Fee Related
- 2002-07-15 EP EP02758340A patent/EP1412353B1/en not_active Expired - Lifetime
- 2002-07-15 US US10/484,070 patent/US6984646B2/en not_active Expired - Fee Related
- 2002-07-15 ES ES02758340T patent/ES2238592T3/es not_active Expired - Lifetime
- 2002-07-15 WO PCT/EP2002/007834 patent/WO2003008413A1/en not_active Ceased
- 2002-07-15 CA CA002453860A patent/CA2453860A1/en not_active Abandoned
- 2002-07-15 JP JP2003513972A patent/JP2005502636A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20040220208A1 (en) | 2004-11-04 |
| EP1412353A1 (en) | 2004-04-28 |
| WO2003008413A1 (en) | 2003-01-30 |
| GB0117506D0 (en) | 2001-09-12 |
| US6984646B2 (en) | 2006-01-10 |
| ES2238592T3 (es) | 2005-09-01 |
| DE60203120T2 (de) | 2006-02-02 |
| EP1412353B1 (en) | 2005-03-02 |
| DE60203120D1 (de) | 2005-04-07 |
| JP2005502636A (ja) | 2005-01-27 |
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