SK283070B6 - Substituované morfolínové deriváty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents
Substituované morfolínové deriváty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK283070B6 SK283070B6 SK839-96A SK83996A SK283070B6 SK 283070 B6 SK283070 B6 SK 283070B6 SK 83996 A SK83996 A SK 83996A SK 283070 B6 SK283070 B6 SK 283070B6
- Authority
- SK
- Slovakia
- Prior art keywords
- phenyl
- trifluoromethyl
- bis
- ethoxy
- fluorophenyl
- Prior art date
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- 150000002780 morpholines Chemical class 0.000 title claims description 20
- 239000003814 drug Substances 0.000 title claims description 13
- 229940124597 therapeutic agent Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 224
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 60
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 229940002612 prodrug Drugs 0.000 claims abstract description 26
- 239000000651 prodrug Substances 0.000 claims abstract description 26
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 16
- 206010047700 Vomiting Diseases 0.000 claims abstract description 15
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 150000002367 halogens Chemical group 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 208000002193 Pain Diseases 0.000 claims abstract description 9
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 8
- 206010027599 migraine Diseases 0.000 claims abstract description 8
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 5
- 206010061218 Inflammation Diseases 0.000 claims abstract description 3
- 230000004054 inflammatory process Effects 0.000 claims abstract description 3
- -1 azetidinil Chemical group 0.000 claims description 180
- 239000000203 mixture Substances 0.000 claims description 94
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 70
- 238000000034 method Methods 0.000 claims description 70
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 26
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 21
- 208000035475 disorder Diseases 0.000 claims description 21
- 108060008037 tachykinin Proteins 0.000 claims description 19
- OIYANYVIFQBNMS-LLVKDONJSA-N (3S)-4-methyl-3-phenylmorpholine Chemical compound C1(=CC=CC=C1)[C@@H]1N(CCOC1)C OIYANYVIFQBNMS-LLVKDONJSA-N 0.000 claims description 18
- 102000003141 Tachykinin Human genes 0.000 claims description 18
- RXXYJBUUGPAHIJ-LLVKDONJSA-N (3s)-3-(4-fluorophenyl)-4-methylmorpholine Chemical compound CN1CCOC[C@@H]1C1=CC=C(F)C=C1 RXXYJBUUGPAHIJ-LLVKDONJSA-N 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 239000002243 precursor Substances 0.000 claims description 14
- 125000001424 substituent group Chemical group 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 9
- 230000008673 vomiting Effects 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 6
- YHCCMWCMNKHTKW-CEXWTWQISA-N (2S)-2-[3,5-bis(trifluoromethyl)phenyl]-2-[(2R,3S)-3-(4-fluorophenyl)-4-methylmorpholin-2-yl]oxyethanol Chemical compound CN1[C@H]([C@H](OCC1)O[C@H](CO)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)C1=CC=C(C=C1)F YHCCMWCMNKHTKW-CEXWTWQISA-N 0.000 claims description 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- AYMJRTPBJMGQTL-ZUSMLRIVSA-N (2R,3S)-3-(4-fluorophenyl)-2-[(1R)-1-[3-fluoro-5-(trifluoromethyl)phenyl]ethoxy]-4-methylmorpholine Chemical compound CN1[C@H]([C@H](OCC1)O[C@H](C)C1=CC(=CC(=C1)C(F)(F)F)F)C1=CC=C(C=C1)F AYMJRTPBJMGQTL-ZUSMLRIVSA-N 0.000 claims description 4
- 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 150000001540 azides Chemical class 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- LIVUQZTUCDTTDD-ZUSMLRIVSA-N CN1[C@H]([C@H](OCC1)O[C@H](C)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)C1=CC=C(C=C1)F Chemical compound CN1[C@H]([C@H](OCC1)O[C@H](C)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)C1=CC=C(C=C1)F LIVUQZTUCDTTDD-ZUSMLRIVSA-N 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 2
- CXEPEPVLLZZYRR-OPYAIIAOSA-N 5-[(2r,3s)-2-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxyethoxy]-3-(4-fluorophenyl)-3-methylmorpholin-4-yl]-1,2-dihydro-1,2,4-triazol-3-one Chemical compound C1([C@@H](CO)O[C@@H]2[C@](N(CCO2)C=2NNC(=O)N=2)(C)C=2C=CC(F)=CC=2)=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CXEPEPVLLZZYRR-OPYAIIAOSA-N 0.000 claims description 2
- 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 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 2
- OHEPRDIJMGVEAO-CEXWTWQISA-N (2S)-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-[(2R,3S)-4-methyl-3-phenylmorpholin-2-yl]oxyethanol Chemical compound CN1CCO[C@@H]([C@@H]1C2=CC=CC=C2)O[C@H](CO)C3=CC(=CC(=C3)F)C(F)(F)F OHEPRDIJMGVEAO-CEXWTWQISA-N 0.000 claims 1
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims 1
- LZTSCEYDCZBRCJ-UHFFFAOYSA-N 1,2-dihydro-1,2,4-triazol-3-one Chemical compound OC=1N=CNN=1 LZTSCEYDCZBRCJ-UHFFFAOYSA-N 0.000 claims 1
- 208000020401 Depressive disease Diseases 0.000 claims 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 2
- 125000004103 aminoalkyl group Chemical group 0.000 abstract 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical group O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- 241000036848 Porzana carolina Species 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
- 239000000243 solution Substances 0.000 description 92
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 88
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 78
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
- 235000019439 ethyl acetate Nutrition 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
- 239000011541 reaction mixture Substances 0.000 description 48
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 42
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- 239000003921 oil Substances 0.000 description 37
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
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- 239000007787 solid Substances 0.000 description 30
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 239000003480 eluent Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
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- 238000003756 stirring Methods 0.000 description 11
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Classifications
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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
- C07D413/06—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 carbon chain containing only aliphatic carbon atoms
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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
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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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
- A61P37/00—Drugs for immunological or allergic disorders
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- 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
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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
- C07D413/14—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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/6533—Six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9326480A GB9326480D0 (en) | 1993-12-29 | 1993-12-29 | Therapeutic agents |
| GB9407189A GB9407189D0 (en) | 1994-04-12 | 1994-04-12 | Therapeutic agents |
| GB9408065A GB9408065D0 (en) | 1994-04-22 | 1994-04-22 | Therapeutic agents |
| GB9416428A GB9416428D0 (en) | 1994-08-15 | 1994-08-15 | Therapeutic agents |
| PCT/GB1994/002819 WO1995018124A1 (en) | 1993-12-29 | 1994-12-23 | Substituted morpholine derivatives and their use as therapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK83996A3 SK83996A3 (en) | 1996-11-06 |
| SK283070B6 true SK283070B6 (sk) | 2003-02-04 |
Family
ID=27451102
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK839-96A SK283070B6 (sk) | 1993-12-29 | 1994-12-23 | Substituované morfolínové deriváty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US5612337A (de) |
| EP (3) | EP0737192B1 (de) |
| JP (2) | JP3071467B2 (de) |
| KR (1) | KR100286412B1 (de) |
| CN (1) | CN1067683C (de) |
| AT (3) | ATE364606T1 (de) |
| BG (1) | BG62616B1 (de) |
| BR (1) | BR9408442A (de) |
| CA (1) | CA2178219C (de) |
| CZ (1) | CZ288176B6 (de) |
| DE (3) | DE69434991T2 (de) |
| DK (1) | DK0737192T3 (de) |
| ES (1) | ES2164758T3 (de) |
| HU (1) | HU221139B1 (de) |
| IL (1) | IL112134A (de) |
| LV (1) | LV11687B (de) |
| NO (1) | NO307090B1 (de) |
| NZ (1) | NZ277839A (de) |
| PL (1) | PL181214B1 (de) |
| RU (1) | RU2131426C1 (de) |
| SG (1) | SG52217A1 (de) |
| SK (1) | SK283070B6 (de) |
| TW (1) | TW449588B (de) |
| WO (1) | WO1995018124A1 (de) |
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| JPH06510034A (ja) * | 1991-08-20 | 1994-11-10 | メルク シヤープ エンド ドーム リミテツド | アザ環式化合物、それらの製造方法、及びそれらを含む医薬組成物 |
| IL106142A (en) * | 1992-06-29 | 1997-03-18 | Merck & Co Inc | Morpholine and thiomorpholine tachykinin receptor antagonists, their preparation and pharmaceutical compositions containing them |
| IL111960A (en) * | 1993-12-17 | 1999-12-22 | Merck & Co Inc | Morpholines and thiomorpholines their preparation and pharmaceutical compositions containing them |
| TW385308B (en) * | 1994-03-04 | 2000-03-21 | Merck & Co Inc | Prodrugs of morpholine tachykinin receptor antagonists |
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1994
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