CA2423251A1 - Morpholin-acetamide derivatives for the treatment of inflammatory diseases - Google Patents
Morpholin-acetamide derivatives for the treatment of inflammatory diseases Download PDFInfo
- Publication number
- CA2423251A1 CA2423251A1 CA002423251A CA2423251A CA2423251A1 CA 2423251 A1 CA2423251 A1 CA 2423251A1 CA 002423251 A CA002423251 A CA 002423251A CA 2423251 A CA2423251 A CA 2423251A CA 2423251 A1 CA2423251 A1 CA 2423251A1
- Authority
- CA
- Canada
- Prior art keywords
- heteroaryl
- formula
- alkyl
- aryl
- methyl
- 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
- 238000011282 treatment Methods 0.000 title claims abstract description 16
- 208000027866 inflammatory disease Diseases 0.000 title claims abstract description 10
- BWRNWWSQZROEOA-UHFFFAOYSA-N 2-morpholin-4-ylacetamide Chemical class NC(=O)CN1CCOCC1 BWRNWWSQZROEOA-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 252
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 122
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 64
- 239000001257 hydrogen Substances 0.000 claims abstract description 60
- 238000000034 method Methods 0.000 claims abstract description 48
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 40
- 101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 claims abstract description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000005977 Ethylene Substances 0.000 claims abstract description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims description 43
- 229910052757 nitrogen Inorganic materials 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- 239000001301 oxygen Substances 0.000 claims description 27
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 26
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
- 239000005864 Sulphur Chemical group 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 229920005989 resin Polymers 0.000 claims description 20
- 239000011347 resin Substances 0.000 claims description 20
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- 239000012453 solvate Substances 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical group 0.000 claims description 16
- 208000006673 asthma Diseases 0.000 claims description 15
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 13
- 125000006239 protecting group Chemical group 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 8
- 239000007790 solid phase Substances 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 150000002466 imines Chemical class 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 14
- 101150020251 NR13 gene Chemical group 0.000 claims 6
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Chemical group 0.000 claims 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- NWSBXZQLWPKCBN-INIZCTEOSA-N n-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-2-(3-sulfamoylphenyl)acetamide Chemical compound NS(=O)(=O)C1=CC=CC(CC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=C1 NWSBXZQLWPKCBN-INIZCTEOSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 185
- 230000008569 process Effects 0.000 abstract description 30
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 238000009472 formulation Methods 0.000 abstract 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 269
- 238000001819 mass spectrum Methods 0.000 description 254
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 246
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 231
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 212
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 132
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 113
- 125000006286 dichlorobenzyl group Chemical group 0.000 description 103
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 79
- -1 oxygen radicals Chemical class 0.000 description 72
- 239000000243 solution Substances 0.000 description 60
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- 239000002904 solvent Substances 0.000 description 47
- 229940093499 ethyl acetate Drugs 0.000 description 43
- 235000019439 ethyl acetate Nutrition 0.000 description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 36
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 34
- 239000007787 solid Substances 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 238000004128 high performance liquid chromatography Methods 0.000 description 29
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 26
- 239000003480 eluent Substances 0.000 description 25
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 22
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 22
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 238000002953 preparative HPLC Methods 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 20
- 235000019198 oils Nutrition 0.000 description 20
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 19
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 19
- 239000012071 phase Substances 0.000 description 19
- 210000003979 eosinophil Anatomy 0.000 description 18
- 229910021529 ammonia Inorganic materials 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 201000010099 disease Diseases 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- 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 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
- 235000019253 formic acid Nutrition 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 238000010828 elution Methods 0.000 description 13
- 235000019441 ethanol Nutrition 0.000 description 13
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 238000005342 ion exchange Methods 0.000 description 12
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 description 11
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 11
- 102000019034 Chemokines Human genes 0.000 description 11
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- 125000003342 alkenyl group Chemical group 0.000 description 11
- 239000002585 base Substances 0.000 description 11
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- 150000002431 hydrogen Chemical class 0.000 description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
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- 125000000896 monocarboxylic acid group Chemical group 0.000 description 9
- 239000002002 slurry Substances 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 8
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- 125000004803 chlorobenzyl group Chemical group 0.000 description 8
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- 125000004093 cyano group Chemical group *C#N 0.000 description 8
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- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
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- 210000000265 leukocyte Anatomy 0.000 description 8
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- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 8
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- 238000000825 ultraviolet detection Methods 0.000 description 7
- DUILGEYLVHGSEE-UHFFFAOYSA-N 2-(oxiran-2-ylmethyl)isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC1CO1 DUILGEYLVHGSEE-UHFFFAOYSA-N 0.000 description 6
- 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 6
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- 206010061218 Inflammation Diseases 0.000 description 6
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- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
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Classifications
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0023902.0 | 2000-09-29 | ||
| GB0023902A GB0023902D0 (en) | 2000-09-29 | 2000-09-29 | Therapeutically useful compounds |
| GB0107644.7 | 2001-03-27 | ||
| GB0107644A GB0107644D0 (en) | 2001-03-27 | 2001-03-27 | Therapeutically useful compounds |
| PCT/GB2001/004345 WO2002026722A1 (en) | 2000-09-29 | 2001-09-28 | Morpholin-acetamide derivatives for the treatment of inflammatory diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2423251A1 true CA2423251A1 (en) | 2002-04-04 |
Family
ID=26245078
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002423251A Abandoned CA2423251A1 (en) | 2000-09-29 | 2001-09-28 | Morpholin-acetamide derivatives for the treatment of inflammatory diseases |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US7101882B2 (https=) |
| EP (1) | EP1324990B1 (https=) |
| JP (1) | JP5089846B2 (https=) |
| KR (1) | KR20030031198A (https=) |
| CN (1) | CN1678594A (https=) |
| AR (1) | AR035205A1 (https=) |
| AU (1) | AU2001290143A1 (https=) |
| BR (1) | BR0114323A (https=) |
| CA (1) | CA2423251A1 (https=) |
| CZ (1) | CZ20031195A3 (https=) |
| ES (1) | ES2527688T3 (https=) |
| HU (1) | HUP0302302A2 (https=) |
| IL (1) | IL155093A0 (https=) |
| MX (1) | MXPA03002814A (https=) |
| NO (1) | NO20031442L (https=) |
| NZ (1) | NZ525056A (https=) |
| PL (1) | PL362711A1 (https=) |
| WO (1) | WO2002026722A1 (https=) |
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| IL155093A0 (en) * | 2000-09-29 | 2003-10-31 | Glaxo Group Ltd | Morpholin-acetamide derivatives for the treatment on inflammatory diseases |
| JP4246490B2 (ja) * | 2000-11-28 | 2009-04-02 | スミスクライン ビーチャム ピー エル シー | オレキシン受容体のアンタゴニストとしてのモルホリン誘導体 |
| GB0207443D0 (en) * | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| TW200400035A (en) | 2002-03-28 | 2004-01-01 | Glaxo Group Ltd | Novel compounds |
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| GB0207449D0 (en) * | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| GB0207445D0 (en) * | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| GB0211759D0 (en) * | 2002-05-22 | 2002-07-03 | Glaxo Group Ltd | Novel compounds |
| GB0212357D0 (en) * | 2002-05-29 | 2002-07-10 | Glaxo Group Ltd | Novel compounds |
| GB0212355D0 (en) * | 2002-05-29 | 2002-07-10 | Glaxo Group Ltd | Novel compounds |
| TWI328009B (en) | 2003-05-21 | 2010-08-01 | Glaxo Group Ltd | Quinoline derivatives as phosphodiesterase inhibitors |
| GB0316290D0 (en) | 2003-07-11 | 2003-08-13 | Glaxo Group Ltd | Novel compounds |
| AR049384A1 (es) | 2004-05-24 | 2006-07-26 | Glaxo Group Ltd | Derivados de purina |
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| GB0418045D0 (en) | 2004-08-12 | 2004-09-15 | Glaxo Group Ltd | Compounds |
| CA2579207C (en) * | 2004-09-08 | 2011-10-18 | Mitsubishi Pharma Corporation | Morpholine compound |
| EP1841780B1 (en) | 2005-01-10 | 2011-07-27 | Glaxo Group Limited | Androstane 17-alpha-carbonate derivatives for use in the treatment of allergic and inflammatory conditions |
| UY29440A1 (es) | 2005-03-25 | 2006-10-02 | Glaxo Group Ltd | Nuevos compuestos |
| UY29439A1 (es) | 2005-03-25 | 2006-10-02 | Glaxo Group Ltd | Nuevos compuestos |
| GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| EP1919884A1 (en) * | 2005-07-21 | 2008-05-14 | AstraZeneca AB | N-benzyl-morpholine derivatives as modulators of the chemokine receptor |
| MX2008013411A (es) | 2006-04-20 | 2008-11-04 | Glaxo Group Ltd | Nuevos compuestos. |
| GB0611587D0 (en) | 2006-06-12 | 2006-07-19 | Glaxo Group Ltd | Novel compounds |
| JP2010501567A (ja) | 2006-08-24 | 2010-01-21 | ノバルティス アクチエンゲゼルシャフト | 代謝系、心血管系および他の障害の処置のためのステアロイル−ＣｏＡ不飽和化酵素（ＳＣＤ）阻害剤としての２−（ピラジン−２−イル）−チアゾールおよび２−（１Ｈ−ピラゾール−３−イル）チアゾール誘導体ならびに関連化合物 |
| KR20090053923A (ko) | 2006-09-22 | 2009-05-28 | 노파르티스 아게 | 헤테로시클릭 유기 화합물 |
| CN101595105B (zh) | 2006-12-20 | 2013-01-23 | 诺瓦提斯公司 | 作为scd抑制剂的2-取代的5元杂环化合物 |
| PE20081889A1 (es) | 2007-03-23 | 2009-03-05 | Smithkline Beecham Corp | Indol carboxamidas como inhibidores de ikk2 |
| JP5791500B2 (ja) | 2008-05-23 | 2015-10-07 | パンミラ ファーマシューティカルズ，エルエルシー． | ５−リポキシゲナーゼ活性化タンパク質阻害剤 |
| ES2383246T3 (es) | 2008-06-05 | 2012-06-19 | Glaxo Group Limited | 4-amino-indazoles |
| ES2566339T3 (es) | 2008-06-05 | 2016-04-12 | Glaxo Group Limited | Derivados de 4-carboxamida indazol útiles como inhibidores de PI3-quinasas |
| KR101036913B1 (ko) * | 2008-12-26 | 2011-05-25 | 주식회사 포스코 | 고로의 머드건과 노즐팁 사이의 틈새 메움용 장치 및 방법 |
| JP5656880B2 (ja) | 2009-03-09 | 2015-01-21 | グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ | Ｐｉ３キナーゼの阻害剤としての４−オキサジアゾール−２−イル−インダゾール |
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| WO2010106016A1 (en) | 2009-03-17 | 2010-09-23 | Glaxo Group Limited | Pyrimidine derivatives used as itk inhibitors |
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| EP2408917A2 (en) | 2009-03-19 | 2012-01-25 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF BTB AND CNC HOMOLOGY 1, BASIC LEUCINE ZIPPER TRANSCRIPTION FACTOR 1 (BACH 1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) SEQUENCE LISTING |
| US20120004281A1 (en) | 2009-03-27 | 2012-01-05 | Merck Sharp & Dohme Corp | RNA Interference Mediated Inhibition of the Nerve Growth Factor Beta Chain (NGFB) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
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2001
- 2001-09-28 IL IL15509301A patent/IL155093A0/xx unknown
- 2001-09-28 CZ CZ20031195A patent/CZ20031195A3/cs unknown
- 2001-09-28 AR ARP010104602A patent/AR035205A1/es not_active Application Discontinuation
- 2001-09-28 HU HU0302302A patent/HUP0302302A2/hu unknown
- 2001-09-28 BR BR0114323-9A patent/BR0114323A/pt not_active IP Right Cessation
- 2001-09-28 MX MXPA03002814A patent/MXPA03002814A/es unknown
- 2001-09-28 KR KR10-2003-7004594A patent/KR20030031198A/ko not_active Withdrawn
- 2001-09-28 US US10/381,767 patent/US7101882B2/en not_active Expired - Lifetime
- 2001-09-28 ES ES01970023.6T patent/ES2527688T3/es not_active Expired - Lifetime
- 2001-09-28 EP EP01970023.6A patent/EP1324990B1/en not_active Expired - Lifetime
- 2001-09-28 CN CNA018196365A patent/CN1678594A/zh active Pending
- 2001-09-28 JP JP2002531106A patent/JP5089846B2/ja not_active Expired - Lifetime
- 2001-09-28 AU AU2001290143A patent/AU2001290143A1/en not_active Abandoned
- 2001-09-28 NZ NZ525056A patent/NZ525056A/en unknown
- 2001-09-28 PL PL01362711A patent/PL362711A1/xx not_active Application Discontinuation
- 2001-09-28 CA CA002423251A patent/CA2423251A1/en not_active Abandoned
- 2001-09-28 WO PCT/GB2001/004345 patent/WO2002026722A1/en not_active Ceased
-
2003
- 2003-03-27 US US10/509,519 patent/US20050222147A1/en not_active Abandoned
- 2003-03-28 NO NO20031442A patent/NO20031442L/no unknown
-
2005
- 2005-11-22 US US11/284,544 patent/US7560548B2/en not_active Expired - Lifetime
-
2009
- 2009-02-24 US US12/391,855 patent/US20090163495A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20060079525A1 (en) | 2006-04-13 |
| JP5089846B2 (ja) | 2012-12-05 |
| IL155093A0 (en) | 2003-10-31 |
| EP1324990B1 (en) | 2014-10-29 |
| CZ20031195A3 (cs) | 2003-09-17 |
| NO20031442D0 (no) | 2003-03-28 |
| BR0114323A (pt) | 2003-07-01 |
| CN1678594A (zh) | 2005-10-05 |
| HUP0302302A2 (hu) | 2003-12-29 |
| AU2001290143A1 (en) | 2002-04-08 |
| NO20031442L (no) | 2003-05-26 |
| US20090163495A1 (en) | 2009-06-25 |
| WO2002026722A1 (en) | 2002-04-04 |
| PL362711A1 (en) | 2004-11-02 |
| KR20030031198A (ko) | 2003-04-18 |
| MXPA03002814A (es) | 2003-10-14 |
| NZ525056A (en) | 2004-11-26 |
| AR035205A1 (es) | 2004-05-05 |
| US7101882B2 (en) | 2006-09-05 |
| US20050222147A1 (en) | 2005-10-06 |
| ES2527688T3 (es) | 2015-01-28 |
| JP2004509952A (ja) | 2004-04-02 |
| EP1324990A1 (en) | 2003-07-09 |
| US20040058923A1 (en) | 2004-03-25 |
| US7560548B2 (en) | 2009-07-14 |
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