DE69330206T2 - Verbindungen zur behandlung von allergischen und entzündlichen erkrankungen - Google Patents
Verbindungen zur behandlung von allergischen und entzündlichen erkrankungenInfo
- Publication number
- DE69330206T2 DE69330206T2 DE69330206T DE69330206T DE69330206T2 DE 69330206 T2 DE69330206 T2 DE 69330206T2 DE 69330206 T DE69330206 T DE 69330206T DE 69330206 T DE69330206 T DE 69330206T DE 69330206 T2 DE69330206 T2 DE 69330206T2
- Authority
- DE
- Germany
- Prior art keywords
- cyano
- methoxyphenyl
- mmol
- cis
- carboxylic acid
- 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
- 230000000172 allergic effect Effects 0.000 title description 3
- 208000010668 atopic eczema Diseases 0.000 title description 2
- 208000027866 inflammatory disease Diseases 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
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- 208000006673 asthma Diseases 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 abstract description 16
- 201000010099 disease Diseases 0.000 abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 15
- 230000005764 inhibitory process Effects 0.000 abstract description 10
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 7
- 230000006433 tumor necrosis factor production Effects 0.000 abstract description 4
- 230000001404 mediated effect Effects 0.000 abstract description 3
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 abstract 1
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 abstract 1
- 230000003197 catalytic effect Effects 0.000 abstract 1
- 230000002255 enzymatic effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 66
- 239000000203 mixture Substances 0.000 description 58
- 239000007787 solid Substances 0.000 description 48
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
- 239000000243 solution Substances 0.000 description 42
- 238000004458 analytical method Methods 0.000 description 37
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 238000003818 flash chromatography Methods 0.000 description 25
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 23
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- 238000000034 method Methods 0.000 description 18
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- 239000012298 atmosphere Substances 0.000 description 10
- 229910052794 bromium Inorganic materials 0.000 description 10
- 229910052740 iodine Inorganic materials 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 102000000589 Interleukin-1 Human genes 0.000 description 9
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- 229910052786 argon Inorganic materials 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
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- 230000002401 inhibitory effect Effects 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- 108010044467 Isoenzymes Proteins 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 5
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 5
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- 239000007903 gelatin capsule Substances 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 4
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 4
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- 102000030621 adenylate cyclase Human genes 0.000 description 4
- 150000001299 aldehydes Chemical group 0.000 description 4
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- 239000002585 base Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
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- DKULVBWFTURTED-UHFFFAOYSA-N 1-[3,4-bis(difluoromethoxy)phenyl]-4-[cyano-[(2-methylpropan-2-yl)oxy]methylidene]cyclohexane-1-carbonitrile Chemical compound C1CC(=C(C#N)OC(C)(C)C)CCC1(C#N)C1=CC=C(OC(F)F)C(OC(F)F)=C1 DKULVBWFTURTED-UHFFFAOYSA-N 0.000 description 3
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- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- A61P37/08—Antiallergic 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/50—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/08—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/30—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reactions not involving the formation of esterified sulfo groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
- C07C319/12—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols by reactions not involving the formation of mercapto groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- External Artificial Organs (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86203092A | 1992-04-02 | 1992-04-02 | |
| US96876292A | 1992-10-30 | 1992-10-30 | |
| PCT/US1993/001991 WO1993019749A1 (en) | 1992-04-02 | 1993-03-05 | Compounds useful for treating allergic and inflammatory diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69330206D1 DE69330206D1 (de) | 2001-06-13 |
| DE69330206T2 true DE69330206T2 (de) | 2002-02-14 |
Family
ID=27127661
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69330206T Expired - Lifetime DE69330206T2 (de) | 1992-04-02 | 1993-03-05 | Verbindungen zur behandlung von allergischen und entzündlichen erkrankungen |
| DE69332987T Expired - Lifetime DE69332987T2 (de) | 1992-04-02 | 1993-03-05 | Verbindungen verwendbar für die Behandlung von Allergien und Entzündungskrankheiten |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69332987T Expired - Lifetime DE69332987T2 (de) | 1992-04-02 | 1993-03-05 | Verbindungen verwendbar für die Behandlung von Allergien und Entzündungskrankheiten |
Country Status (16)
| Country | Link |
|---|---|
| EP (3) | EP1380571A1 (enExample) |
| JP (1) | JP2873090B2 (enExample) |
| KR (1) | KR950700731A (enExample) |
| AT (2) | ATE240290T1 (enExample) |
| AU (2) | AU705566B2 (enExample) |
| CY (2) | CY2331B1 (enExample) |
| DE (2) | DE69330206T2 (enExample) |
| DK (2) | DK0919544T3 (enExample) |
| ES (2) | ES2157923T3 (enExample) |
| MA (1) | MA22859A1 (enExample) |
| MY (1) | MY109561A (enExample) |
| OA (1) | OA10101A (enExample) |
| PH (1) | PH31379A (enExample) |
| PT (2) | PT633776E (enExample) |
| RO (1) | RO115872B1 (enExample) |
| RU (1) | RU2136656C1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005053672A1 (ja) * | 2003-12-04 | 2005-06-16 | Santen Pharmaceutical Co., Ltd. | シロミラストまたはその塩を有効成分とする掻痒治療剤 |
| JP2005187458A (ja) * | 2003-12-04 | 2005-07-14 | Santen Pharmaceut Co Ltd | シロミラストまたはその塩を有効成分とする掻痒治療剤 |
| CN102772411A (zh) * | 2006-07-05 | 2012-11-14 | 奈科明有限责任公司 | 用于治疗炎症性肺部疾病的HMG-CoA还原酶抑制剂与磷酸二酯酶4抑制剂的组合 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1793383C3 (de) * | 1968-09-10 | 1979-03-01 | Knoll Ag, 6700 Ludwigshafen | 4-Cyan-4-phenyl-aminocyclohexane und deren wasserlösliche Salze, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel |
| US4795757A (en) * | 1984-09-04 | 1989-01-03 | Rorer Pharmaceutical Corporation | Bisarylamines |
| DE3621581A1 (de) * | 1986-06-27 | 1988-01-07 | Merck Patent Gmbh | Polymerisierbare fluessigkristallmaterialien |
| US5096906A (en) * | 1986-12-31 | 1992-03-17 | University Of Virginia Alumni Patents Foundation | Method of inhibiting the activity of leukocyte derived cytokines |
| AU3738293A (en) * | 1992-04-02 | 1993-11-08 | Smithkline Beecham Corporation | Compounds useful for treating allergic and inflammatory diseases |
| EP0633771A4 (en) * | 1992-04-02 | 1995-02-22 | Smithkline Beecham Corporation | Compounds. |
| WO1993019751A1 (en) * | 1992-04-02 | 1993-10-14 | Smithkline Beecham Corporation | Compounds useful for treating inflammatory diseases and inhibiting production of tumor necrosis factor |
-
1993
- 1993-03-05 PT PT93907233T patent/PT633776E/pt unknown
- 1993-03-05 DK DK98204466T patent/DK0919544T3/da active
- 1993-03-05 DK DK93907233T patent/DK0633776T3/da active
- 1993-03-05 RO RO94-01601A patent/RO115872B1/ro unknown
- 1993-03-05 AT AT98204466T patent/ATE240290T1/de active
- 1993-03-05 DE DE69330206T patent/DE69330206T2/de not_active Expired - Lifetime
- 1993-03-05 RU RU94045291A patent/RU2136656C1/ru active
- 1993-03-05 JP JP5517446A patent/JP2873090B2/ja not_active Expired - Lifetime
- 1993-03-05 AT AT93907233T patent/ATE200980T1/de active
- 1993-03-05 DE DE69332987T patent/DE69332987T2/de not_active Expired - Lifetime
- 1993-03-05 EP EP03076447A patent/EP1380571A1/en not_active Withdrawn
- 1993-03-05 EP EP03076446A patent/EP1420011A1/en not_active Withdrawn
- 1993-03-05 ES ES93907233T patent/ES2157923T3/es not_active Expired - Lifetime
- 1993-03-05 EP EP98204466A patent/EP0919544B1/en not_active Expired - Lifetime
- 1993-03-05 PT PT98204466T patent/PT919544E/pt unknown
- 1993-03-05 ES ES98204466T patent/ES2197421T3/es not_active Expired - Lifetime
- 1993-03-29 PH PH45956A patent/PH31379A/en unknown
- 1993-03-31 MY MYPI93000561A patent/MY109561A/en unknown
- 1993-04-01 MA MA23150A patent/MA22859A1/fr unknown
-
1994
- 1994-09-29 OA OA60565A patent/OA10101A/en unknown
- 1994-10-04 KR KR1019940703523A patent/KR950700731A/ko active Granted
-
1997
- 1997-08-08 AU AU33229/97A patent/AU705566B2/en not_active Expired
-
1999
- 1999-06-24 AU AU36759/99A patent/AU724115B2/en not_active Expired
-
2002
- 2002-11-05 CY CY0200061A patent/CY2331B1/xx unknown
-
2004
- 2004-08-27 CY CY0400066A patent/CY2474B1/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0919544B1 (en) | 2003-05-14 |
| AU724115B2 (en) | 2000-09-14 |
| EP1420011A1 (en) | 2004-05-19 |
| CY2331B1 (en) | 2004-02-06 |
| DE69332987D1 (de) | 2003-06-18 |
| AU3322997A (en) | 1997-10-23 |
| RU94045291A (ru) | 1996-09-27 |
| CY2474B1 (en) | 2005-06-03 |
| DK0633776T3 (da) | 2001-08-27 |
| ES2157923T3 (es) | 2001-09-01 |
| KR950700731A (ko) | 1995-02-20 |
| ATE240290T1 (de) | 2003-05-15 |
| JP2873090B2 (ja) | 1999-03-24 |
| EP0919544A1 (en) | 1999-06-02 |
| DE69332987T2 (de) | 2004-05-19 |
| ATE200980T1 (de) | 2001-05-15 |
| PH31379A (en) | 1998-10-29 |
| OA10101A (en) | 1996-12-18 |
| AU3675999A (en) | 1999-08-19 |
| PT633776E (pt) | 2001-10-31 |
| MA22859A1 (fr) | 1993-12-31 |
| PT919544E (pt) | 2003-09-30 |
| DE69330206D1 (de) | 2001-06-13 |
| EP1380571A1 (en) | 2004-01-14 |
| AU705566B2 (en) | 1999-05-27 |
| RO115872B1 (ro) | 2000-07-28 |
| HK1012263A1 (en) | 1999-07-30 |
| RU2136656C1 (ru) | 1999-09-10 |
| ES2197421T3 (es) | 2004-01-01 |
| DK0919544T3 (da) | 2003-09-15 |
| HK1022467A1 (en) | 2000-08-11 |
| JPH07508508A (ja) | 1995-09-21 |
| MY109561A (en) | 1997-02-28 |
| KR100344711B1 (enExample) | 2003-05-01 |
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