DE60214428T2 - 1, 4-dihydro-1, 4-diphenylpyridin-derivate - Google Patents
1, 4-dihydro-1, 4-diphenylpyridin-derivate Download PDFInfo
- Publication number
- DE60214428T2 DE60214428T2 DE60214428T DE60214428T DE60214428T2 DE 60214428 T2 DE60214428 T2 DE 60214428T2 DE 60214428 T DE60214428 T DE 60214428T DE 60214428 T DE60214428 T DE 60214428T DE 60214428 T2 DE60214428 T2 DE 60214428T2
- Authority
- DE
- Germany
- Prior art keywords
- compounds
- general formula
- amino
- methyl
- mmol
- 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.)
- Expired - Lifetime
Links
- RLTOXDSOOSYULO-UHFFFAOYSA-N 1,4-diphenyl-4h-pyridine Chemical class C1=CN(C=2C=CC=CC=2)C=CC1C1=CC=CC=C1 RLTOXDSOOSYULO-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 78
- -1 C C 1 -C 6 -alkoxy Chemical group 0.000 claims description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 12
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 6
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 5
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical group C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 3
- 230000008578 acute process Effects 0.000 claims description 3
- 230000006020 chronic inflammation Effects 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 238000002483 medication Methods 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 83
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 239000002904 solvent Substances 0.000 description 33
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 26
- 238000001816 cooling Methods 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- 102000052502 human ELANE Human genes 0.000 description 23
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 20
- 239000003480 eluent Substances 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- 238000010992 reflux Methods 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 229920002549 elastin Polymers 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 102000016942 Elastin Human genes 0.000 description 6
- 108010014258 Elastin Proteins 0.000 description 6
- 108010028275 Leukocyte Elastase Proteins 0.000 description 6
- 102000016799 Leukocyte elastase Human genes 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 210000000224 granular leucocyte Anatomy 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 102000016387 Pancreatic elastase Human genes 0.000 description 5
- 108010067372 Pancreatic elastase Proteins 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 210000000440 neutrophil Anatomy 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 4
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- 206010014561 Emphysema Diseases 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 238000000338 in vitro Methods 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
- 238000004519 manufacturing process Methods 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 0 CC(*)*=C(*)[C@@]1C(C(O*)=O)=C(*)N(C(II)=I**)C(*)=C1C(*)=O Chemical compound CC(*)*=C(*)[C@@]1C(C(O*)=O)=C(*)N(C(II)=I**)C(*)=C1C(*)=O 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 102100033174 Neutrophil elastase Human genes 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 201000010251 cutis laxa Diseases 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 238000006911 enzymatic reaction Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 210000003622 mature neutrocyte Anatomy 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 238000010490 three component reaction Methods 0.000 description 3
- VGVXOXSRINSIFO-UHFFFAOYSA-N 3-(diethylaminomethyl)aniline Chemical compound CCN(CC)CC1=CC=CC(N)=C1 VGVXOXSRINSIFO-UHFFFAOYSA-N 0.000 description 2
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 2
- JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 2
- NXAIGPFVFJVPQT-UHFFFAOYSA-N 5-acetyl-2-amino-4-(4-cyanophenyl)-6-methyl-1-[3-(trifluoromethyl)phenyl]-4h-pyridine-3-carbonitrile Chemical compound CC(=O)C1=C(C)N(C=2C=C(C=CC=2)C(F)(F)F)C(N)=C(C#N)C1C1=CC=C(C#N)C=C1 NXAIGPFVFJVPQT-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000003246 elastolytic effect Effects 0.000 description 2
- YQFZOZQVKJGHCI-UHFFFAOYSA-N ethyl 5-acetyl-2-amino-4-(4-cyanophenyl)-6-methyl-1-[3-(trifluoromethyl)phenyl]-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(N)N(C=2C=C(C=CC=2)C(F)(F)F)C(C)=C(C(C)=O)C1C1=CC=C(C#N)C=C1 YQFZOZQVKJGHCI-UHFFFAOYSA-N 0.000 description 2
- GYXLPEWQLNLUJH-UHFFFAOYSA-N ethyl 5-acetyl-4-(4-cyanophenyl)-2,6-dimethyl-1-(3-methylphenyl)-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)N(C=2C=C(C)C=CC=2)C(C)=C(C(C)=O)C1C1=CC=C(C#N)C=C1 GYXLPEWQLNLUJH-UHFFFAOYSA-N 0.000 description 2
- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 229910052722 tritium Inorganic materials 0.000 description 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- XYGVIBXOJOOCFR-BTJKTKAUSA-N (z)-but-2-enedioic acid;8-chloro-6-(2-fluorophenyl)-1-methyl-4h-imidazo[1,5-a][1,4]benzodiazepine Chemical compound OC(=O)\C=C/C(O)=O.C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F XYGVIBXOJOOCFR-BTJKTKAUSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- UGBLISDIHDMHJX-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]butan-1-one;hydrochloride Chemical compound [Cl-].COC1=CC=CC=C1N1CC[NH+](CCCC(=O)C=2C=CC(F)=CC=2)CC1 UGBLISDIHDMHJX-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- MATJPVGBSAQWAC-UHFFFAOYSA-N 2-cyano-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CC#N MATJPVGBSAQWAC-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical class C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- AGFSYSXYGGUNCD-UHFFFAOYSA-N 3-iodo-5-(trifluoromethyl)aniline Chemical compound NC1=CC(I)=CC(C(F)(F)F)=C1 AGFSYSXYGGUNCD-UHFFFAOYSA-N 0.000 description 1
- VTFGJEYZCUWSAM-UHFFFAOYSA-N 3-methoxy-5-(trifluoromethyl)aniline Chemical compound COC1=CC(N)=CC(C(F)(F)F)=C1 VTFGJEYZCUWSAM-UHFFFAOYSA-N 0.000 description 1
- XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 description 1
- MVRPHHIECBYHNA-UHFFFAOYSA-N 4-(3-methylanilino)pent-3-en-2-one Chemical compound CC(=O)C=C(C)NC1=CC=CC(C)=C1 MVRPHHIECBYHNA-UHFFFAOYSA-N 0.000 description 1
- BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
- KXRHFRNOXDARAF-UHFFFAOYSA-N 4-[3-(trifluoromethyl)anilino]pent-3-en-2-one Chemical compound CC(=O)C=C(C)NC1=CC=CC(C(F)(F)F)=C1 KXRHFRNOXDARAF-UHFFFAOYSA-N 0.000 description 1
- NSXHOHFFHVBIEG-UHFFFAOYSA-N 4-[3-amino-5-(trifluoromethyl)anilino]pent-3-en-2-one Chemical compound CC(=O)C=C(C)NC1=CC(N)=CC(C(F)(F)F)=C1 NSXHOHFFHVBIEG-UHFFFAOYSA-N 0.000 description 1
- JAMBBCAZYXICMO-UHFFFAOYSA-N 4-[3-iodo-5-(trifluoromethyl)anilino]pent-3-en-2-one Chemical compound CC(=O)C=C(C)NC1=CC(I)=CC(C(F)(F)F)=C1 JAMBBCAZYXICMO-UHFFFAOYSA-N 0.000 description 1
- QYHKFSZKGGIXIZ-UHFFFAOYSA-N 4-[3-methoxy-5-(trifluoromethyl)anilino]pent-3-en-2-one Chemical compound COC1=CC(NC(C)=CC(C)=O)=CC(C(F)(F)F)=C1 QYHKFSZKGGIXIZ-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- KZSXRDLXTFEHJM-UHFFFAOYSA-N 5-(trifluoromethyl)benzene-1,3-diamine Chemical compound NC1=CC(N)=CC(C(F)(F)F)=C1 KZSXRDLXTFEHJM-UHFFFAOYSA-N 0.000 description 1
- IYNILYVAEOIOBO-UHFFFAOYSA-N 5-acetyl-2-amino-4-(4-cyanophenyl)-6-methyl-1-[3-(trifluoromethyl)phenyl]-4h-pyridine-3-carboxamide Chemical compound CC(=O)C1=C(C)N(C=2C=C(C=CC=2)C(F)(F)F)C(N)=C(C(N)=O)C1C1=CC=C(C#N)C=C1 IYNILYVAEOIOBO-UHFFFAOYSA-N 0.000 description 1
- XVLKGMJKPWCPEF-UHFFFAOYSA-N 5-acetyl-4-(4-cyanophenyl)-2-imino-n,n,6-trimethyl-1-[3-(trifluoromethyl)phenyl]-3,4-dihydropyridine-3-carboxamide Chemical compound N=C1C(C(=O)N(C)C)C(C=2C=CC(=CC=2)C#N)C(C(C)=O)=C(C)N1C1=CC=CC(C(F)(F)F)=C1 XVLKGMJKPWCPEF-UHFFFAOYSA-N 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- AWYMFBJJKFTCFO-UHFFFAOYSA-N C(C1)C2C1CCC2 Chemical compound C(C1)C2C1CCC2 AWYMFBJJKFTCFO-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 101710145505 Fiber protein Proteins 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 206010037394 Pulmonary haemorrhage Diseases 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 206010001053 acute respiratory failure Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical class BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-UHFFFAOYSA-N 0.000 description 1
- ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical class OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- VFNGKCDDZUSWLR-UHFFFAOYSA-N disulfuric acid Chemical class OS(=O)(=O)OS(O)(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical class CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- SAUHDLZFJLGGGE-VQHVLOKHSA-N ethyl (e)-3-[3-(trifluoromethyl)anilino]but-2-enoate Chemical compound CCOC(=O)\C=C(/C)NC1=CC=CC(C(F)(F)F)=C1 SAUHDLZFJLGGGE-VQHVLOKHSA-N 0.000 description 1
- LCECRWMMJQTWMI-UHFFFAOYSA-N ethyl 5-acetyl-2-amino-1-[3-amino-5-(trifluoromethyl)phenyl]-4-(4-cyanophenyl)-6-methyl-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(N)N(C=2C=C(C=C(N)C=2)C(F)(F)F)C(C)=C(C(C)=O)C1C1=CC=C(C#N)C=C1 LCECRWMMJQTWMI-UHFFFAOYSA-N 0.000 description 1
- IUWVDURXQOYQEP-UHFFFAOYSA-N ethyl 5-acetyl-2-amino-4-(4-bromophenyl)-6-methyl-1-(3-nitrophenyl)-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(N)N(C=2C=C(C=CC=2)[N+]([O-])=O)C(C)=C(C(C)=O)C1C1=CC=C(Br)C=C1 IUWVDURXQOYQEP-UHFFFAOYSA-N 0.000 description 1
- FUWNGXILMPFYNH-UHFFFAOYSA-N ethyl 5-acetyl-2-amino-4-(4-bromophenyl)-6-methyl-1-[3-(trifluoromethyl)phenyl]-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(N)N(C=2C=C(C=CC=2)C(F)(F)F)C(C)=C(C(C)=O)C1C1=CC=C(Br)C=C1 FUWNGXILMPFYNH-UHFFFAOYSA-N 0.000 description 1
- UHRDEPFHLSWMPH-UHFFFAOYSA-N ethyl 5-acetyl-2-amino-4-(4-cyanophenyl)-1-[3-(diethylaminomethyl)phenyl]-6-methyl-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(N)N(C=2C=C(CN(CC)CC)C=CC=2)C(C)=C(C(C)=O)C1C1=CC=C(C#N)C=C1 UHRDEPFHLSWMPH-UHFFFAOYSA-N 0.000 description 1
- UBFPUKHZXZRQQB-UHFFFAOYSA-N ethyl 5-acetyl-2-amino-4-(4-cyanophenyl)-1-[3-iodo-5-(trifluoromethyl)phenyl]-6-methyl-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(N)N(C=2C=C(C=C(I)C=2)C(F)(F)F)C(C)=C(C(C)=O)C1C1=CC=C(C#N)C=C1 UBFPUKHZXZRQQB-UHFFFAOYSA-N 0.000 description 1
- WZCBTFHYRRSLIW-UHFFFAOYSA-N ethyl 5-acetyl-2-amino-4-(4-cyanophenyl)-1-[3-methoxy-5-(trifluoromethyl)phenyl]-6-methyl-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(N)N(C=2C=C(C=C(OC)C=2)C(F)(F)F)C(C)=C(C(C)=O)C1C1=CC=C(C#N)C=C1 WZCBTFHYRRSLIW-UHFFFAOYSA-N 0.000 description 1
- UKVSSZIRXGXKTQ-UHFFFAOYSA-N ethyl 5-acetyl-2-amino-4-(4-cyanophenyl)-6-methyl-1-(3-methylphenyl)-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(N)N(C=2C=C(C)C=CC=2)C(C)=C(C(C)=O)C1C1=CC=C(C#N)C=C1 UKVSSZIRXGXKTQ-UHFFFAOYSA-N 0.000 description 1
- FVVCCXZWQAHBAS-UHFFFAOYSA-N ethyl 5-acetyl-2-amino-6-methyl-1-[3-(trifluoromethyl)phenyl]-4-[4-(trifluoromethyl)phenyl]-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(N)N(C=2C=C(C=CC=2)C(F)(F)F)C(C)=C(C(C)=O)C1C1=CC=C(C(F)(F)F)C=C1 FVVCCXZWQAHBAS-UHFFFAOYSA-N 0.000 description 1
- YGKISBJTNIBYSW-UHFFFAOYSA-N ethyl 5-acetyl-4-(4-bromophenyl)-6-methyl-1-[3-(trifluoromethyl)phenyl]-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN(C=2C=C(C=CC=2)C(F)(F)F)C(C)=C(C(C)=O)C1C1=CC=C(Br)C=C1 YGKISBJTNIBYSW-UHFFFAOYSA-N 0.000 description 1
- AZJGYWFUWTZENE-UHFFFAOYSA-N ethyl 5-acetyl-4-(4-cyanophenyl)-6-methyl-1-[3-(trifluoromethyl)phenyl]-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN(C=2C=C(C=CC=2)C(F)(F)F)C(C)=C(C(C)=O)C1C1=CC=C(C#N)C=C1 AZJGYWFUWTZENE-UHFFFAOYSA-N 0.000 description 1
- ZCCRTLHMKZZEPT-UHFFFAOYSA-N ethyl 6-amino-1,4-bis(4-chlorophenyl)-5-cyano-2-methyl-4h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)N(C=2C=CC(Cl)=CC=2)C(N)=C(C#N)C1C1=CC=C(Cl)C=C1 ZCCRTLHMKZZEPT-UHFFFAOYSA-N 0.000 description 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 231100000516 lung damage Toxicity 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical class CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- 150000005451 methyl sulfates Chemical class 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical class [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0130553 | 2001-12-20 | ||
| GB0130553A GB2383326A (en) | 2001-12-20 | 2001-12-20 | Antiinflammatory dihydropyridines |
| GB0216664 | 2002-07-17 | ||
| GB0216664A GB2390849A (en) | 2002-07-17 | 2002-07-17 | 3-Acyl-1,4-dihydro-1,4-di(phenyl/azinyl/diazinyl)pyridine derivatives for use as human neutrophil elastase inhibitors |
| PCT/EP2002/013931 WO2003053930A1 (en) | 2001-12-20 | 2002-12-09 | 1,4-dihydro-1,4-diphenylpyridine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60214428D1 DE60214428D1 (de) | 2006-10-12 |
| DE60214428T2 true DE60214428T2 (de) | 2007-09-20 |
Family
ID=26246892
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60214428T Expired - Lifetime DE60214428T2 (de) | 2001-12-20 | 2002-12-09 | 1, 4-dihydro-1, 4-diphenylpyridin-derivate |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7199136B2 (https=) |
| EP (1) | EP1458682B1 (https=) |
| JP (1) | JP4486817B2 (https=) |
| AU (1) | AU2002361992A1 (https=) |
| CA (1) | CA2470813A1 (https=) |
| DE (1) | DE60214428T2 (https=) |
| ES (1) | ES2271365T3 (https=) |
| WO (1) | WO2003053930A1 (https=) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0219896D0 (en) | 2002-08-27 | 2002-10-02 | Bayer Ag | Dihydropyridine derivatives |
| US7566723B2 (en) * | 2002-09-10 | 2009-07-28 | Bayer Healthcare Ag | 1-phenyl1-3,4-dihydropyrimidin-2(1H)-one derivatives and their use |
| SE0302487D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | Novel compounds |
| JP5134248B2 (ja) * | 2004-02-19 | 2013-01-30 | バイエル・ファルマ・アクチェンゲゼルシャフト | ジヒドロピリジノン誘導体 |
| CA2557271C (en) | 2004-02-26 | 2012-08-21 | Bayer Healthcare Ag | 1,4-diaryl-dihydropyrimidin-2-ones and their use as human neutrophil elastase inhibitors |
| ES2428503T3 (es) | 2004-02-26 | 2013-11-08 | Bayer Intellectual Property Gmbh | 1,4-Diaril-dihidropirimidin-2-onas y su uso como inhibidores de elastasa de neutrófilos humanos |
| BRPI0614290A2 (pt) | 2005-08-08 | 2011-03-22 | Argenta Discovery Ltd | derivados de biciclo [ 2.2.1 ] hept-7-ilamina e seus usos |
| GB0516313D0 (en) | 2005-08-08 | 2005-09-14 | Argenta Discovery Ltd | Azole derivatives and their uses |
| DE102007019691A1 (de) | 2007-04-26 | 2008-10-30 | Bayer Healthcare Ag | Verwendung von acyclisch substituierten Furopyrimidin-Derivaten zur Behandlung der pulmonalen arteriellen Hypertonie |
| DE102007019690A1 (de) | 2007-04-26 | 2008-10-30 | Bayer Healthcare Ag | Verwendung von cyclisch substituierten Furopyrimidin-Derivaten zur Behandlung der pulmonalen arteriellen Hypertonie |
| DE102007027800A1 (de) | 2007-06-16 | 2008-12-18 | Bayer Healthcare Ag | Substituierte bicyclische Heteroaryl-Verbindungen und ihre Verwendung |
| DE102007027799A1 (de) | 2007-06-16 | 2008-12-18 | Bayer Healthcare Ag | Substituierte Furopyrimidine und ihre Verwendung |
| DE102007051762A1 (de) | 2007-10-30 | 2009-05-07 | Bayer Healthcare Ag | Substituierte Pyrrolotriazine und ihre Verwendung |
| DE102007054786A1 (de) | 2007-11-16 | 2009-05-20 | Bayer Healthcare Ag | Trisubstituierte Furopyrimidine und ihre Verwendung |
| PT2229358E (pt) | 2007-12-14 | 2011-06-29 | Pulmagen Therapeutics Asthma Ltd | Indoles e sua utilização terapêutica |
| DE102008007400A1 (de) | 2008-02-04 | 2009-08-06 | Bayer Healthcare Ag | Substituierte Furane und ihre Verwendung |
| DE102009004197A1 (de) * | 2009-01-09 | 2010-07-15 | Bayer Schering Pharma Aktiengesellschaft | Heterocyclisch anellierte Diaryldihydropyrimidin-Derivate und ihre Verwendung |
| GB0902648D0 (en) | 2009-02-17 | 2009-04-01 | Argenta Discovery Ltd | Pharmaceutical compounds and compositions |
| SG174134A1 (en) | 2009-02-17 | 2011-10-28 | Chiesi Farma Spa | Triazolopyridine derivatives as p38 map kinase inhibitors |
| GB0918924D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Azaindole derivatives |
| GB0918922D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminopyridine derivatives |
| GB0918923D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminothiazole derivatives |
| GB201009731D0 (en) | 2010-06-10 | 2010-07-21 | Pulmagen Therapeutics Inflamma | Kinase inhibitors |
| DK2788349T3 (en) | 2011-12-09 | 2017-01-30 | Chiesi Farm Spa | kinase inhibitors |
| KR20140105459A (ko) | 2011-12-09 | 2014-09-01 | 키에시 파르마슈티시 엣스. 피. 에이. | 키나아제 억제제 |
| BR112014013178A2 (pt) | 2011-12-09 | 2017-06-13 | Chiesi Farm Spa | composto, composição farmacêutica e uso de um composto |
| US20140221335A1 (en) | 2013-02-06 | 2014-08-07 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9115093B2 (en) | 2013-03-04 | 2015-08-25 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| RU2015151886A (ru) | 2013-06-06 | 2017-06-08 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Ингибиторы киназ |
| US9440930B2 (en) | 2014-07-31 | 2016-09-13 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9475779B2 (en) | 2014-07-31 | 2016-10-25 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9290457B2 (en) * | 2014-07-31 | 2016-03-22 | Boehringer Ingelheim International Gmbh | Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9657015B2 (en) | 2014-07-31 | 2017-05-23 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9458113B2 (en) | 2014-07-31 | 2016-10-04 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9958484B2 (en) * | 2015-07-08 | 2018-05-01 | Qualcomm Incorporated | Apparatus and method for measuring load current by applying compensated gain to voltage derived from drain-to-source voltage of power gating device |
| TW201720828A (zh) | 2015-11-23 | 2017-06-16 | 赫孚孟拉羅股份公司 | 治療性化合物及組合物以及其使用方法 |
| EP3394059B1 (en) | 2015-12-23 | 2020-11-25 | Chiesi Farmaceutici S.p.A. | 1-(3-tert-butyl-phenyl)-3-(4-([1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro- naphthalen-1-yl)-urea derivatives and their use as p38 mapk inhibitors |
| AR107164A1 (es) | 2015-12-23 | 2018-03-28 | Chiesi Farm Spa | INHIBIDORES DE QUINASA p38 |
| EP3394058B1 (en) | 2015-12-23 | 2020-10-14 | Chiesi Farmaceutici S.p.A. | N-[3-(3-{4-[[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl} -ureido)-phenyl]-methanesulfonamide derivatives and their use as p38 mapk inhibitors |
| JP7034942B2 (ja) | 2016-05-05 | 2022-03-14 | エフ．ホフマン－ラ ロシュ アーゲー | ピラゾール誘導体、その組成物及び治療的使用 |
| CN109890817B (zh) | 2016-09-06 | 2022-06-17 | 豪夫迈·罗氏有限公司 | 8-(氮杂环丁烷-1-基)-[1,2,4]三唑并[1,5-a]吡啶基化合物、其组合物和应用方法 |
| EP3562809B1 (en) | 2016-12-29 | 2021-06-09 | F. Hoffmann-La Roche AG | Pyrazolopyrimidine compounds and methods of use thereof |
| CN110494434B (zh) | 2017-03-14 | 2022-05-24 | 豪夫迈·罗氏有限公司 | 吡唑并氯苯基化合物、其组合物及其使用方法 |
| CN110678467B (zh) | 2017-05-22 | 2023-06-13 | 豪夫迈·罗氏有限公司 | 治疗化合物和组合物及其使用方法 |
| WO2018215389A1 (en) | 2017-05-22 | 2018-11-29 | F. Hoffmann-La Roche Ag | Therapeutic compounds and compositions, and methods of use thereof |
| US10364245B2 (en) | 2017-06-07 | 2019-07-30 | Chiesi Farmaceutici S.P.A. | Kinase inhibitors |
| EP3740488A1 (en) | 2018-01-15 | 2020-11-25 | F. Hoffmann-La Roche AG | Pyrazolopyrimidine compounds as jak inhibitors |
| JP2020015705A (ja) * | 2018-07-27 | 2020-01-30 | 住友化学株式会社 | アニリン化合物の製造方法 |
| US20200399274A1 (en) | 2019-06-18 | 2020-12-24 | Genentech, Inc. | Tetrazole-substituted pyrazolopyrimidine inhibitors of jak kinases and uses thereof |
| WO2020257143A1 (en) | 2019-06-18 | 2020-12-24 | Genentech, Inc. | Pyrazolopyrimidine aryl ether inhibitors of jak kinases and uses thereof |
| CA3140024A1 (en) | 2019-06-18 | 2020-12-24 | Mark Edward Zak | Pyrazolopyrimidine sulfone inhibitors of jak kinases and uses thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2753946A1 (de) * | 1977-12-03 | 1979-06-13 | Bayer Ag | 1-n-aryl-1,4-dihydropyridine und ihre verwendung als arzneimittel |
| DE3222367A1 (de) * | 1982-06-15 | 1983-12-15 | Bayer Ag, 5090 Leverkusen | Verwendung von 1,4-dihydropyridinen in antiarteriosklerotika und deren herstellung |
| DE4011695A1 (de) * | 1990-04-11 | 1991-10-17 | Bayer Ag | Verwendung von n-alkylierten 1,4-dihydropyridindicarbonsaeureestern als arzneimittel, neue verbindungen und verfahren zu ihrer herstellung |
| DE4328884A1 (de) * | 1993-08-27 | 1995-03-02 | Bayer Ag | Verwendung von N-alkylierten 1,4-Dihydropyridincarbonsäureestern als Arzneimittel |
| JP3337829B2 (ja) * | 1994-07-29 | 2002-10-28 | 日研化学株式会社 | １，４−ジヒドロピリジン化合物 |
-
2002
- 2002-12-09 DE DE60214428T patent/DE60214428T2/de not_active Expired - Lifetime
- 2002-12-09 AU AU2002361992A patent/AU2002361992A1/en not_active Abandoned
- 2002-12-09 EP EP02796589A patent/EP1458682B1/en not_active Expired - Lifetime
- 2002-12-09 WO PCT/EP2002/013931 patent/WO2003053930A1/en not_active Ceased
- 2002-12-09 CA CA002470813A patent/CA2470813A1/en not_active Abandoned
- 2002-12-09 ES ES02796589T patent/ES2271365T3/es not_active Expired - Lifetime
- 2002-12-09 JP JP2003554646A patent/JP4486817B2/ja not_active Expired - Fee Related
- 2002-12-09 US US10/498,967 patent/US7199136B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2470813A1 (en) | 2003-07-03 |
| US7199136B2 (en) | 2007-04-03 |
| JP4486817B2 (ja) | 2010-06-23 |
| US20050165014A1 (en) | 2005-07-28 |
| DE60214428D1 (de) | 2006-10-12 |
| WO2003053930A1 (en) | 2003-07-03 |
| EP1458682B1 (en) | 2006-08-30 |
| EP1458682A1 (en) | 2004-09-22 |
| JP2005517666A (ja) | 2005-06-16 |
| AU2002361992A1 (en) | 2003-07-09 |
| ES2271365T3 (es) | 2007-04-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60214428T2 (de) | 1, 4-dihydro-1, 4-diphenylpyridin-derivate | |
| DE69727308T2 (de) | HETEROCYCLENDERIVATE DIE FAKTOR Xa HEMMEN | |
| DE60012223T2 (de) | Harnstoffderivate wirksam als muscarinrezeptor-antagonisten | |
| DE60021282T2 (de) | Carbamat-derivate als muscarin-rezeptor antonisten | |
| JP5134248B2 (ja) | ジヒドロピリジノン誘導体 | |
| DE69021501T2 (de) | Anti-entzündende 4-aminophenol-derivate. | |
| BRPI0721451A2 (pt) | Compostos de 4-piperidiniluréia como inibidores de epóxido hidrolase solúvel | |
| EP1812430B1 (de) | Substituierte phenylaminothiazole und ihre verwendung | |
| US4370328A (en) | Cardiac stimulant 1-(3- or 4-substituted piperidino)phthalazines | |
| EP1568688B1 (en) | Therapeutic agent for respiratory disease containing 4-hydroxypiperidine derivative as active ingredient | |
| KR20090064480A (ko) | 가용성 에폭시드 히드롤라아제 억제제로서의 페닐우레아 화합물 | |
| US20040009988A1 (en) | Bioisosteric bensamide derivatives and their use as apob-100 secretion inhibitors | |
| US4188391A (en) | 4-[4-(Substituted)piperidino]quinazoline cardiac stimulants | |
| DD284679A5 (de) | Verfahren zur herstellung von adenosin 5'-carboamidderivate | |
| DE69613457T2 (de) | 5-(4-subst.-piperidinyl-1)-3-aryl-pentansäure derivate als tachykinin rezeptor antagonisten | |
| DE60032016T2 (de) | Cycloamin-ccr5-rezeptor-antagonisten | |
| Chapleo et al. | Heteroaromatic analogs of the. alpha. 2-adrenoreceptor partial agonist clonidine | |
| DE4443891A1 (de) | Heterocyclisch substituierte Oxy-phenyl-(phenyl)glycinolamide | |
| US6956046B2 (en) | 4-hydroxypiperidine derivatives having analgesic activity | |
| CA2727769A1 (en) | Novel compounds active as muscarinic receptor antagonists | |
| DE69615019T2 (de) | Benzopyrane und diese enthaltende pharmazeutische zusammenstellungen | |
| EP0739892A2 (de) | Chromon-Derivate | |
| DE3782378T2 (de) | Dihydropyridinderivate und deren pharmazeutische zusammensetzungen. | |
| EP1470108B1 (en) | 1,4-dihydropyridine and pyridine compounds as calcium channel blockers | |
| CH663616A5 (de) | 1,4-dihydropyridin-derivate und sie enthaltende pharmazeutische zubereitungen. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: BAYER SCHERING PHARMA AKTIENGESELLSCHAFT, 1335, DE |