CN101014580B - 吗啉化合物 - Google Patents
吗啉化合物 Download PDFInfo
- Publication number
- CN101014580B CN101014580B CN2005800301370A CN200580030137A CN101014580B CN 101014580 B CN101014580 B CN 101014580B CN 2005800301370 A CN2005800301370 A CN 2005800301370A CN 200580030137 A CN200580030137 A CN 200580030137A CN 101014580 B CN101014580 B CN 101014580B
- Authority
- CN
- China
- Prior art keywords
- methyl
- sulphur
- morpholine
- ethanamide
- optional
- 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 - Fee Related
Links
- -1 Morpholine compound Chemical class 0.000 title claims description 493
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 540
- 150000003839 salts Chemical class 0.000 claims abstract description 79
- 239000003814 drug Substances 0.000 claims abstract description 56
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 498
- 239000005864 Sulphur Substances 0.000 claims description 395
- 238000000034 method Methods 0.000 claims description 389
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 207
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 182
- 239000001301 oxygen Substances 0.000 claims description 64
- 229910052760 oxygen Inorganic materials 0.000 claims description 64
- 230000014509 gene expression Effects 0.000 claims description 53
- 125000001118 alkylidene group Chemical group 0.000 claims description 47
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
- 125000005843 halogen group Chemical group 0.000 claims description 39
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 32
- 125000001072 heteroaryl group Chemical class 0.000 claims description 31
- 239000000126 substance Substances 0.000 claims description 30
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- 125000004429 atom Chemical group 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 229940073608 benzyl chloride Drugs 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 201000009890 sinusitis Diseases 0.000 claims description 18
- DYBRCIRRFKVZDL-UHFFFAOYSA-N [S]C1=NC=CS1 Chemical compound [S]C1=NC=CS1 DYBRCIRRFKVZDL-UHFFFAOYSA-N 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 10
- 201000008937 atopic dermatitis Diseases 0.000 claims description 10
- 208000006673 asthma Diseases 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 201000003068 rheumatic fever Diseases 0.000 claims description 9
- 206010002198 Anaphylactic reaction Diseases 0.000 claims description 8
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 8
- 206010010741 Conjunctivitis Diseases 0.000 claims description 8
- 208000011231 Crohn disease Diseases 0.000 claims description 8
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 8
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 8
- 201000010105 allergic rhinitis Diseases 0.000 claims description 8
- 230000036783 anaphylactic response Effects 0.000 claims description 8
- 208000003455 anaphylaxis Diseases 0.000 claims description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 7
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical compound [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 claims description 4
- CRZIAMCADJKTOG-UHFFFAOYSA-N C(C)(=O)NC=1C=CC(=C(C1)[As](O)(O)=O)O Chemical compound C(C)(=O)NC=1C=CC(=C(C1)[As](O)(O)=O)O CRZIAMCADJKTOG-UHFFFAOYSA-N 0.000 claims description 3
- PRDVNVAUNKVQNC-UHFFFAOYSA-N NC1=CC(C2=C(C3)SC([S])=N2)=C3C=C1 Chemical compound NC1=CC(C2=C(C3)SC([S])=N2)=C3C=C1 PRDVNVAUNKVQNC-UHFFFAOYSA-N 0.000 claims description 3
- VTFUDZHSXVDDIL-UHFFFAOYSA-N OC(=O)C1=CC=C([S])C=C1 Chemical compound OC(=O)C1=CC=C([S])C=C1 VTFUDZHSXVDDIL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 4
- 150000001721 carbon Chemical group 0.000 claims 2
- 239000012453 solvate Substances 0.000 abstract description 25
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 abstract description 21
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 abstract description 21
- 238000011282 treatment Methods 0.000 abstract description 7
- 208000027866 inflammatory disease Diseases 0.000 abstract description 5
- 230000002265 prevention Effects 0.000 abstract description 4
- 239000001257 hydrogen Substances 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 2
- 125000000732 arylene group Chemical group 0.000 abstract 1
- 230000001900 immune effect Effects 0.000 abstract 1
- 208000026278 immune system disease Diseases 0.000 abstract 1
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
- 239000000047 product Substances 0.000 description 322
- 239000002585 base Substances 0.000 description 317
- 238000005160 1H NMR spectroscopy Methods 0.000 description 243
- 239000007787 solid Substances 0.000 description 236
- 125000001424 substituent group Chemical group 0.000 description 95
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000002904 solvent Substances 0.000 description 88
- 239000000203 mixture Substances 0.000 description 78
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- 239000012230 colorless oil Substances 0.000 description 63
- QGJAVGUBPSOFKS-UHFFFAOYSA-N morpholine;dihydrochloride Chemical compound Cl.Cl.C1COCCN1 QGJAVGUBPSOFKS-UHFFFAOYSA-N 0.000 description 59
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 58
- 239000011541 reaction mixture Substances 0.000 description 55
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 230000002829 reductive effect Effects 0.000 description 49
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- 238000000605 extraction Methods 0.000 description 47
- 239000012046 mixed solvent Substances 0.000 description 45
- CWERGRDVMFNCDR-UHFFFAOYSA-N alpha-mercaptoacetic acid Natural products OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 239000007788 liquid Substances 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
- 238000001035 drying Methods 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 238000003756 stirring Methods 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 38
- 238000006243 chemical reaction Methods 0.000 description 38
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
- 239000013078 crystal Substances 0.000 description 31
- 235000019270 ammonium chloride Nutrition 0.000 description 29
- 239000000843 powder Substances 0.000 description 28
- 238000010898 silica gel chromatography Methods 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- 238000003810 ethyl acetate extraction Methods 0.000 description 23
- 239000003921 oil Substances 0.000 description 22
- 229910052801 chlorine Inorganic materials 0.000 description 20
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 17
- 238000001816 cooling Methods 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- 125000001544 thienyl group Chemical group 0.000 description 17
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 125000000335 thiazolyl group Chemical group 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 15
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 14
- 125000003545 alkoxy group Chemical group 0.000 description 14
- 210000000222 eosinocyte Anatomy 0.000 description 14
- 235000011121 sodium hydroxide Nutrition 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 125000004076 pyridyl group Chemical group 0.000 description 13
- VNXFBBRJLDEDSP-UHFFFAOYSA-N C(C)(=O)OC.[S] Chemical compound C(C)(=O)OC.[S] VNXFBBRJLDEDSP-UHFFFAOYSA-N 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 235000015320 potassium carbonate Nutrition 0.000 description 12
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 12
- 125000002098 pyridazinyl group Chemical group 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 125000003368 amide group Chemical group 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 125000002541 furyl group Chemical group 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 125000005605 benzo group Chemical group 0.000 description 10
- 125000003373 pyrazinyl group Chemical group 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 102000009410 Chemokine receptor Human genes 0.000 description 9
- 108050000299 Chemokine receptor Proteins 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 9
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 9
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 9
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 125000001153 fluoro group Chemical group F* 0.000 description 8
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 description 8
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
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- 208000003926 Myelitis Diseases 0.000 description 7
- 150000004646 arylidenes Chemical group 0.000 description 7
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 230000036039 immunity Effects 0.000 description 7
- WKNMKGVLOWGGOU-UHFFFAOYSA-N 2-aminoacetamide;hydron;chloride Chemical compound Cl.NCC(N)=O WKNMKGVLOWGGOU-UHFFFAOYSA-N 0.000 description 6
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
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- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000005956 isoquinolyl group Chemical group 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 125000006591 (C2-C6) alkynylene group Chemical group 0.000 description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 5
- NTVCMEJZWNSEFW-ICSRJNTNSA-N 4-(diaminomethylideneamino)-n-[[(2s)-1-[(2s)-3-hydroxy-2-(naphthalen-2-ylsulfonylamino)propanoyl]pyrrolidin-2-yl]methyl]butanamide Chemical compound NC(N)=NCCCC(=O)NC[C@@H]1CCCN1C(=O)[C@H](CO)NS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 NTVCMEJZWNSEFW-ICSRJNTNSA-N 0.000 description 5
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- 238000004519 manufacturing process Methods 0.000 description 5
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- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 4
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- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical group [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 4
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 description 4
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- BNJMRELGMDUDDB-UHFFFAOYSA-N $l^{1}-sulfanylbenzene Chemical compound [S]C1=CC=CC=C1 BNJMRELGMDUDDB-UHFFFAOYSA-N 0.000 description 3
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 3
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- VSJSXTHAYDUTBI-UHFFFAOYSA-N pyridin-4-yloxyboronic acid Chemical compound OB(O)OC1=CC=NC=C1 VSJSXTHAYDUTBI-UHFFFAOYSA-N 0.000 description 1
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- 229920006395 saturated elastomer Polymers 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- RXNKCUXXNGWROA-JEDNCBNOSA-N tert-butyl (2s)-2,4-diamino-4-oxobutanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)[C@@H](N)CC(N)=O RXNKCUXXNGWROA-JEDNCBNOSA-N 0.000 description 1
- IQPIGJGLXGFGCP-FNORWQNLSA-N tert-butyl (e)-3-(6-chloropyridin-3-yl)prop-2-enoate Chemical compound CC(C)(C)OC(=O)\C=C\C1=CC=C(Cl)N=C1 IQPIGJGLXGFGCP-FNORWQNLSA-N 0.000 description 1
- AVBWFKGSSKCNFV-UHFFFAOYSA-N tert-butyl 2-amino-3-methylmorpholine-4-carboxylate Chemical compound CC1N(CCOC1N)C(=O)OC(C)(C)C AVBWFKGSSKCNFV-UHFFFAOYSA-N 0.000 description 1
- DOMTZTVJNZKUNX-UHFFFAOYSA-N tert-butyl 3-aminopropanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)CCN DOMTZTVJNZKUNX-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- 229940125670 thienopyridine Drugs 0.000 description 1
- 239000002175 thienopyridine Substances 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- VSGXHZUTTFLSBC-UHFFFAOYSA-N thiophene-3-thiol Chemical compound SC=1C=CSC=1 VSGXHZUTTFLSBC-UHFFFAOYSA-N 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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-
- C—CHEMISTRY; METALLURGY
- 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
- C07D413/02—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
- 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
-
- C—CHEMISTRY; METALLURGY
- 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
-
- 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
- C07D417/02—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 containing two hetero rings
- C07D417/12—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 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D417/14—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 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Otolaryngology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
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| JP2004261655 | 2004-09-08 | ||
| JP261655/2004 | 2004-09-08 | ||
| PCT/JP2005/017002 WO2006028284A1 (ja) | 2004-09-08 | 2005-09-08 | モルホリン化合物 |
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| CN101014580A CN101014580A (zh) | 2007-08-08 |
| CN101014580B true CN101014580B (zh) | 2011-05-04 |
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| DE602006001511D1 (de) * | 2005-02-04 | 2008-07-31 | Ctg Pharma S R L | Neue 4-aminochinolinderivate als antimalariamittel |
| CN101212967A (zh) | 2005-05-10 | 2008-07-02 | 因塞特公司 | 吲哚胺2,3-双加氧酶调节剂及其用法 |
| CA2634198C (en) | 2005-12-20 | 2014-06-03 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| US8030303B2 (en) * | 2006-07-11 | 2011-10-04 | Mitsubishi Tanabe Pharma Corporation | Salt of morpholine compound |
| WO2008036652A2 (en) * | 2006-09-19 | 2008-03-27 | Incyte Corporation | Amidines as modulators of indoleamine 2,3-dioxygenase |
| CL2007002650A1 (es) | 2006-09-19 | 2008-02-08 | Incyte Corp | Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras. |
| CA2663057C (en) * | 2006-09-19 | 2015-12-08 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| WO2008058178A1 (en) * | 2006-11-08 | 2008-05-15 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| US8273766B2 (en) | 2007-04-04 | 2012-09-25 | Kowa Company, Ltd. | Tetrahydroisoquinoline compound |
| AU2009268739B2 (en) | 2008-07-08 | 2014-05-08 | Incyte Holdings Corporation | 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase |
| WO2015012332A1 (ja) * | 2013-07-24 | 2015-01-29 | 田辺三菱製薬株式会社 | 眼科疾患治療剤 |
| HUE049337T2 (hu) | 2013-11-08 | 2020-09-28 | Incyte Holdings Corp | Eljárás indolamin-2,3-dioxigenáz inhibitor elõállítására |
| WO2020203822A1 (ja) * | 2019-03-29 | 2020-10-08 | 千寿製薬株式会社 | 血管新生を伴う網膜疾患の治療又は予防のための併用医薬 |
| EP4021898B1 (en) * | 2019-08-26 | 2024-05-29 | Stichting Amsterdam UMC | Inhibition of mycobacterial type vii secretion |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002026722A1 (en) * | 2000-09-29 | 2002-04-04 | Glaxo Group Limited | Morpholin-acetamide derivatives for the treatment of inflammatory diseases |
| WO2004004731A1 (en) * | 2002-07-02 | 2004-01-15 | F. Hoffmann-La Roche Ag | 2, 5-substituted pyrimidine derivatives as ccr-3 receptor antagonists ix |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4870074A (en) | 1986-04-30 | 1989-09-26 | Dainippon Pharmaceutical Co., Ltd. | Substituted benzamide derivatives, for enhancing gastrointestinal motility |
| JPS63264467A (ja) | 1986-04-30 | 1988-11-01 | Dainippon Pharmaceut Co Ltd | ベンズアミド誘導体 |
| JPH03148276A (ja) * | 1989-11-01 | 1991-06-25 | Yoshitomi Pharmaceut Ind Ltd | 光学活性なピリドンカルボン酸化合物 |
| AU1208397A (en) | 1995-12-28 | 1997-07-28 | Takeda Chemical Industries Ltd. | Diphenylmethane derivatives as mip-1alpha/rantes receptor antagonists |
| CA2259927A1 (en) | 1996-07-12 | 1998-01-22 | Leukosite, Inc. | Chemokine receptor antagonists and methods of use therefor |
| EP0916668A4 (en) | 1996-07-29 | 2000-08-16 | Banyu Pharma Co Ltd | CHEMOKINE RECEPTOR ANTAGONISTS |
| AU5522498A (en) | 1996-12-13 | 1998-07-03 | Merck & Co., Inc. | Substituted aryl piperazines as modulators of chemokine receptor activity |
| CA2329821A1 (en) | 1998-04-27 | 1999-11-04 | Dashyant Dhanak | Ccr-3 receptor antagonists |
| CA2329777A1 (en) | 1998-04-27 | 1999-11-04 | Dashyant Dhanak | Ccr-3 receptor antagonists |
| EP1131290B1 (en) | 1998-11-20 | 2008-02-20 | F. Hoffmann-La Roche Ag | Piperidine ccr-3 receptor antagonists |
| WO2000034278A1 (fr) | 1998-12-04 | 2000-06-15 | Toray Industries, Inc. | Derives triazolo, et inhibiteurs de chimiokines contenant ces derives comme ingredient actif |
| WO2000053600A1 (fr) * | 1999-03-11 | 2000-09-14 | Banyu Pharmaceutical Co., Ltd. | Derives piperidiniques |
| PL350904A1 (en) | 1999-03-26 | 2003-02-10 | Astrazeneca Ab | Novel compounds |
| SE9902987D0 (sv) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| AU2001280187A1 (en) | 2000-08-28 | 2002-03-13 | Toray Industries, Inc. | Cyclic amine derivatives |
| EP1324991B1 (en) | 2000-09-29 | 2006-11-15 | Glaxo Group Limited | Compounds useful in the treatment of inflammatory diseases |
| GB0104050D0 (en) | 2001-02-19 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| EP1389616B1 (en) | 2001-04-27 | 2011-07-27 | Mitsubishi Tanabe Pharma Corporation | 3,4-Dihalobenzylpiperidine derivatives and their medical use |
| GB0207436D0 (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 |
| GB0207443D0 (en) | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| GB0207439D0 (en) | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| GB0208158D0 (en) | 2002-03-28 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
| GB0207445D0 (en) | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| GB0212355D0 (en) | 2002-05-29 | 2002-07-10 | Glaxo Group Ltd | Novel compounds |
| GB0212357D0 (en) | 2002-05-29 | 2002-07-10 | Glaxo Group Ltd | Novel compounds |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002026722A1 (en) * | 2000-09-29 | 2002-04-04 | Glaxo Group Limited | Morpholin-acetamide derivatives for the treatment of inflammatory diseases |
| WO2004004731A1 (en) * | 2002-07-02 | 2004-01-15 | F. Hoffmann-La Roche Ag | 2, 5-substituted pyrimidine derivatives as ccr-3 receptor antagonists ix |
Also Published As
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| PT1801108E (pt) | 2012-12-03 |
| US7935700B2 (en) | 2011-05-03 |
| DK1801108T3 (da) | 2013-02-18 |
| KR20070099528A (ko) | 2007-10-09 |
| PL1801108T3 (pl) | 2013-04-30 |
| IN2014CN03493A (US06903085-20050607-C00010.png) | 2015-07-03 |
| ES2396419T3 (es) | 2013-02-21 |
| TWI367209B (US06903085-20050607-C00010.png) | 2012-07-01 |
| KR101011848B1 (ko) | 2011-02-01 |
| JPWO2006028284A1 (ja) | 2008-05-08 |
| CN101014580A (zh) | 2007-08-08 |
| CA2579207A1 (en) | 2006-03-16 |
| EP1801108B9 (en) | 2013-11-20 |
| EP1801108A1 (en) | 2007-06-27 |
| TW200619212A (en) | 2006-06-16 |
| WO2006028284A1 (ja) | 2006-03-16 |
| EP1801108A4 (en) | 2010-10-13 |
| JP4970946B2 (ja) | 2012-07-11 |
| US20070265257A1 (en) | 2007-11-15 |
| EP1801108B1 (en) | 2012-11-14 |
| CA2579207C (en) | 2011-10-18 |
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