DE69124459T3 - Zyklosporine - Google Patents
ZyklosporineInfo
- Publication number
- DE69124459T3 DE69124459T3 DE69124459T DE69124459T DE69124459T3 DE 69124459 T3 DE69124459 T3 DE 69124459T3 DE 69124459 T DE69124459 T DE 69124459T DE 69124459 T DE69124459 T DE 69124459T DE 69124459 T3 DE69124459 T3 DE 69124459T3
- Authority
- DE
- Germany
- Prior art keywords
- meleu
- hydroxy
- ciclosporin
- mebmt
- meval
- 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
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 title claims abstract description 67
- 229930182912 cyclosporin Natural products 0.000 title claims abstract description 59
- 229960001265 ciclosporin Drugs 0.000 title claims description 111
- 108010036949 Cyclosporine Proteins 0.000 title claims description 59
- 108010036941 Cyclosporins Proteins 0.000 claims abstract description 30
- 102000001493 Cyclophilins Human genes 0.000 claims abstract description 15
- 108010068682 Cyclophilins Proteins 0.000 claims abstract description 15
- 208000030507 AIDS Diseases 0.000 claims abstract description 10
- 208000037859 AIDS-related disorder Diseases 0.000 claims abstract description 4
- 230000002265 prevention Effects 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 95
- 229930105110 Cyclosporin A Natural products 0.000 claims description 34
- AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 claims description 34
- XJODGRWDFZVTKW-LURJTMIESA-N (2s)-4-methyl-2-(methylamino)pentanoic acid Chemical group CN[C@H](C(O)=O)CC(C)C XJODGRWDFZVTKW-LURJTMIESA-N 0.000 claims description 22
- AHQFCPOIMVMDEZ-UNISNWAASA-N (e,2s,3r,4r)-3-hydroxy-4-methyl-2-(methylamino)oct-6-enoic acid Chemical group CN[C@H](C(O)=O)[C@H](O)[C@H](C)C\C=C\C AHQFCPOIMVMDEZ-UNISNWAASA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 11
- 238000000855 fermentation Methods 0.000 claims description 8
- 230000004151 fermentation Effects 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 238000003556 assay Methods 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 claims description 6
- 230000002538 fungal effect Effects 0.000 claims description 5
- KSPIYJQBLVDRRI-WDSKDSINSA-N N-methyl-L-isoleucine Chemical compound CC[C@H](C)[C@H](NC)C(O)=O KSPIYJQBLVDRRI-WDSKDSINSA-N 0.000 claims description 4
- RPJPZDVUUKWPGT-FOIHOXPVSA-N nim811 Chemical compound CC[C@H](C)[C@@H]1N(C)C(=O)CN(C)C(=O)[C@H](CC)NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC1=O RPJPZDVUUKWPGT-FOIHOXPVSA-N 0.000 claims description 4
- -1 γ-Hydroxy-MeLeu Chemical compound 0.000 claims description 4
- 238000012286 ELISA Assay Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000002860 competitive effect Effects 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims 2
- 235000015097 nutrients Nutrition 0.000 claims 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 210000004027 cell Anatomy 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 16
- 230000001506 immunosuppresive effect Effects 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 210000004366 CD4-positive T-lymphocyte Anatomy 0.000 description 11
- 239000001963 growth medium Substances 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 229920001817 Agar Polymers 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 239000008272 agar Substances 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- DFZMWWCBMPCKFD-DTLHCQOUSA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s)-30-ethyl-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-24-(2-hydroxy-2-methylpropyl)-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacon Chemical compound CC[C@@H]1NC(=O)C([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)(C)O)N(C)C(=O)CN(C)C1=O DFZMWWCBMPCKFD-DTLHCQOUSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241000725303 Human immunodeficiency virus Species 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 239000008187 granular material Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 230000036983 biotransformation Effects 0.000 description 4
- 229940041514 candida albicans extract Drugs 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
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- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 235000011149 sulphuric acid Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000006257 total synthesis reaction Methods 0.000 description 4
- 239000012138 yeast extract Substances 0.000 description 4
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 241000921533 Nonomuraea dietziae Species 0.000 description 3
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 230000036436 anti-hiv Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000000120 cytopathologic effect Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
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- 230000002441 reversible effect Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
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- 239000007858 starting material Substances 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
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- ZMKGDQSIRSGUDJ-VSROPUKISA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-30-propyl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,1 Chemical compound CCC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O ZMKGDQSIRSGUDJ-VSROPUKISA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 2
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- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
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- ZMKGDQSIRSGUDJ-UHFFFAOYSA-N NVa2 cyclosporine Natural products CCCC1NC(=O)C(C(O)C(C)CC=CC)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O ZMKGDQSIRSGUDJ-UHFFFAOYSA-N 0.000 description 2
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
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Classifications
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
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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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
- C07K7/645—Cyclosporins; Related peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/911—Microorganisms using fungi
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/27—Cyclic peptide or cyclic protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Gastroenterology & Hepatology (AREA)
- Communicable Diseases (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- AIDS & HIV (AREA)
- Transplantation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909023859A GB9023859D0 (en) | 1990-11-02 | 1990-11-02 | Chemical products |
| GB909023971A GB9023971D0 (en) | 1990-11-05 | 1990-11-05 | New use of a cyclosporin derivative |
| GB909023970A GB9023970D0 (en) | 1990-11-05 | 1990-11-05 | New use of a cyclosporin derivative |
| GB909023972A GB9023972D0 (en) | 1990-11-05 | 1990-11-05 | New use of a cyclosporin derivative |
| GB919116836A GB9116836D0 (en) | 1991-08-05 | 1991-08-05 | Organic compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE69124459D1 DE69124459D1 (de) | 1997-03-13 |
| DE69124459T2 DE69124459T2 (de) | 1997-07-10 |
| DE69124459T3 true DE69124459T3 (de) | 2001-05-31 |
Family
ID=27517009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69124459T Expired - Lifetime DE69124459T3 (de) | 1990-11-02 | 1991-10-30 | Zyklosporine |
Country Status (24)
| Country | Link |
|---|---|
| US (3) | US5767069A (en:Method) |
| EP (1) | EP0484281B2 (en:Method) |
| JP (1) | JP2740775B2 (en:Method) |
| KR (1) | KR100203556B1 (en:Method) |
| AT (1) | ATE148469T1 (en:Method) |
| AU (1) | AU649277B2 (en:Method) |
| CA (1) | CA2054590C (en:Method) |
| CY (1) | CY2159B1 (en:Method) |
| CZ (1) | CZ280909B6 (en:Method) |
| DE (1) | DE69124459T3 (en:Method) |
| DK (1) | DK0484281T4 (en:Method) |
| ES (1) | ES2095926T5 (en:Method) |
| FI (1) | FI111730B (en:Method) |
| GR (2) | GR3022592T3 (en:Method) |
| HU (1) | HU212674B (en:Method) |
| IE (1) | IE913824A1 (en:Method) |
| IL (1) | IL99912A (en:Method) |
| MX (1) | MX9101869A (en:Method) |
| MY (1) | MY134806A (en:Method) |
| NZ (1) | NZ240421A (en:Method) |
| PL (1) | PL168609B1 (en:Method) |
| PT (1) | PT99410B (en:Method) |
| SA (1) | SA92120344B1 (en:Method) |
| SK (1) | SK278808B6 (en:Method) |
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1991
- 1991-10-30 DE DE69124459T patent/DE69124459T3/de not_active Expired - Lifetime
- 1991-10-30 SK SK3297-91A patent/SK278808B6/sk not_active IP Right Cessation
- 1991-10-30 EP EP91810841A patent/EP0484281B2/en not_active Expired - Lifetime
- 1991-10-30 FI FI915135A patent/FI111730B/fi not_active IP Right Cessation
- 1991-10-30 ES ES91810841T patent/ES2095926T5/es not_active Expired - Lifetime
- 1991-10-30 DK DK91810841T patent/DK0484281T4/da active
- 1991-10-30 CZ CS913297A patent/CZ280909B6/cs not_active IP Right Cessation
- 1991-10-30 AT AT91810841T patent/ATE148469T1/de not_active IP Right Cessation
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- 1991-10-31 PL PL91292248A patent/PL168609B1/pl unknown
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- 1991-11-01 IE IE382491A patent/IE913824A1/en not_active IP Right Cessation
- 1991-11-01 KR KR1019910019402A patent/KR100203556B1/ko not_active Expired - Lifetime
- 1991-11-01 MY MYPI91002021A patent/MY134806A/en unknown
- 1991-11-01 JP JP3287501A patent/JP2740775B2/ja not_active Expired - Lifetime
- 1991-11-01 HU HU913446A patent/HU212674B/hu unknown
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- 1995-04-24 US US08/427,312 patent/US5767069A/en not_active Expired - Lifetime
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