ES2242214T3 - Compuestos y metodos inmunosupresores. - Google Patents
Compuestos y metodos inmunosupresores.Info
- Publication number
- ES2242214T3 ES2242214T3 ES97908794T ES97908794T ES2242214T3 ES 2242214 T3 ES2242214 T3 ES 2242214T3 ES 97908794 T ES97908794 T ES 97908794T ES 97908794 T ES97908794 T ES 97908794T ES 2242214 T3 ES2242214 T3 ES 2242214T3
- Authority
- ES
- Spain
- Prior art keywords
- triptolide
- compound according
- compound
- alkyl
- cells
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 77
- 238000000034 method Methods 0.000 title abstract description 28
- 239000003018 immunosuppressive agent Substances 0.000 title description 19
- 238000011282 treatment Methods 0.000 claims abstract description 49
- 230000001506 immunosuppresive effect Effects 0.000 claims abstract description 23
- -1 ion carboxylate Chemical class 0.000 claims description 30
- 230000035558 fertility Effects 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 11
- 208000024908 graft versus host disease Diseases 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 208000006673 asthma Diseases 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 206010062016 Immunosuppression Diseases 0.000 claims description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 238000002054 transplantation Methods 0.000 claims description 5
- 239000003981 vehicle Substances 0.000 claims description 5
- 239000004472 Lysine Substances 0.000 claims description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000129 anionic group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- 150000001768 cations Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 229910021645 metal ion Inorganic materials 0.000 claims description 3
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- QHQZEEGNGSZBOL-UHFFFAOYSA-N 2-(aminomethyl)-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(CO)(CO)CO QHQZEEGNGSZBOL-UHFFFAOYSA-N 0.000 claims 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical compound NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- DFBIRQPKNDILPW-CIVMWXNOSA-N Triptolide Chemical class O=C1OCC([C@@H]2C3)=C1CC[C@]2(C)[C@]12O[C@H]1[C@@H]1O[C@]1(C(C)C)[C@@H](O)[C@]21[C@H]3O1 DFBIRQPKNDILPW-CIVMWXNOSA-N 0.000 abstract description 97
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 14
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 5
- 231100000053 low toxicity Toxicity 0.000 abstract description 4
- YKUJZZHGTWVWHA-UHFFFAOYSA-N triptolide Natural products COC12CC3OC3(C(C)C)C(O)C14OC4CC5C6=C(CCC25C)C(=O)OC6 YKUJZZHGTWVWHA-UHFFFAOYSA-N 0.000 description 88
- 210000004027 cell Anatomy 0.000 description 41
- 239000000203 mixture Substances 0.000 description 40
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 31
- 241000699670 Mus sp. Species 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 230000000694 effects Effects 0.000 description 19
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 17
- 150000002148 esters Chemical group 0.000 description 16
- 239000000523 sample Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- GLBMIEFQNYULDO-UFZHVSJGSA-M triptosar Chemical compound [Na+].O=C1OCC([C@@H]2C3)=C1CC[C@]2(C)[C@]12O[C@H]1[C@@H]1O[C@]1(C(C)C)[C@@H](OC(=O)CCC([O-])=O)[C@]21[C@H]3O1 GLBMIEFQNYULDO-UFZHVSJGSA-M 0.000 description 14
- 102000000589 Interleukin-1 Human genes 0.000 description 13
- 108010002352 Interleukin-1 Proteins 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 230000004083 survival effect Effects 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 229940124589 immunosuppressive drug Drugs 0.000 description 11
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 210000002216 heart Anatomy 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 230000035755 proliferation Effects 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 9
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000001629 suppression Effects 0.000 description 8
- 230000001988 toxicity Effects 0.000 description 8
- 231100000419 toxicity Toxicity 0.000 description 8
- 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 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 241000830536 Tripterygium wilfordii Species 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 210000001550 testis Anatomy 0.000 description 7
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
- 229930105110 Cyclosporin A Natural products 0.000 description 6
- 108010036949 Cyclosporine Proteins 0.000 description 6
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 206010052779 Transplant rejections Diseases 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
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- 239000002904 solvent Substances 0.000 description 6
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 239000012981 Hank's balanced salt solution Substances 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 5
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 5
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- 150000003254 radicals Chemical class 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
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- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
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- XLMXUUQMSMKFMH-UZRURVBFSA-N 2-hydroxyethyl (z,12r)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC(=O)OCCO XLMXUUQMSMKFMH-UZRURVBFSA-N 0.000 description 3
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
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- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 3
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- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
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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
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
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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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
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- Pulmonology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
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|---|---|---|---|
| US609277 | 1996-03-01 | ||
| US08/609,277 US5663335A (en) | 1996-03-01 | 1996-03-01 | Immunosuppressive compounds and methods |
Publications (1)
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|---|---|
| ES2242214T3 true ES2242214T3 (es) | 2005-11-01 |
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| ES97908794T Expired - Lifetime ES2242214T3 (es) | 1996-03-01 | 1997-02-28 | Compuestos y metodos inmunosupresores. |
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|---|---|
| US (1) | US5663335A (enExample) |
| EP (1) | EP0907652B1 (enExample) |
| JP (1) | JP4267697B2 (enExample) |
| CN (1) | CN1133637C (enExample) |
| AT (1) | ATE296304T1 (enExample) |
| AU (2) | AU2125897A (enExample) |
| CA (1) | CA2248266C (enExample) |
| DE (1) | DE69733353T2 (enExample) |
| DK (1) | DK0907652T3 (enExample) |
| ES (1) | ES2242214T3 (enExample) |
| PT (1) | PT907652E (enExample) |
| WO (2) | WO1997031920A1 (enExample) |
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| US5880116A (en) * | 1996-12-13 | 1999-03-09 | Neurocal International | Use of celastrol to treat alzheimer's disease |
| US5972998A (en) * | 1997-05-23 | 1999-10-26 | Hoechst Marion Roussel, Inc. | Triptolide derivatives useful in the treatment of autoimmune diseases |
| KR20010012820A (ko) * | 1997-05-23 | 2001-02-26 | 게리 디. 스트리트 | 자가 면역 질환의 치료에 유용한 신규 트리프톨라이드유도체 |
| CN1257507A (zh) * | 1997-05-23 | 2000-06-21 | 赫斯特·马里昂·罗素公司 | 适合用于自身免疫性疾病治疗的新的雷公藤内酯衍生物 |
| US6004999A (en) * | 1997-05-23 | 1999-12-21 | Hoechst Marion Roussel, Inc. | Triptolide derivatives useful in the treatment of autoimmune diseases |
| EP1375488B1 (en) * | 1998-09-02 | 2006-08-02 | Pharmagenesis, Inc. | Triptolide prodrugs having high aqueous solubility |
| US6150539A (en) * | 1998-09-02 | 2000-11-21 | Pharmagenesis, Inc. | Triptolide prodrugs having high aqueous solubility |
| US6548537B1 (en) | 1998-09-02 | 2003-04-15 | Pharmagenesis, Inc. | Triptolide prodrugs having high aqueous solubility |
| JP2002536320A (ja) * | 1999-02-02 | 2002-10-29 | カー・イュー・ルーベン・リサーチ・アンド・ディベロップメント | プテリジン誘導体の免疫抑制作用 |
| US6329148B1 (en) | 1999-02-16 | 2001-12-11 | The Board Of Trustees Of The Leland Stanford University | Combined therapy of diterpenoid triepoxides and death domain receptor ligands for synergistic killing of tumor cells |
| WO2000063212A1 (en) * | 1999-04-16 | 2000-10-26 | Chengdu Diao Pharmaceutical Group Company Limited | Derivatives of triptolide, and preparation and uses thereof |
| US7323471B1 (en) * | 1999-08-13 | 2008-01-29 | Dor Biopharma, Inc. | Topical azathioprine for the treatment of oral autoimmune diseases |
| US6294546B1 (en) * | 1999-08-30 | 2001-09-25 | The Broad Of Trustees Of The Leland Stanford Junior University | Uses of diterpenoid triepoxides as an anti-proliferative agent |
| US6620843B2 (en) * | 2001-01-19 | 2003-09-16 | Pharmagenesis | Anticancer treatment using triptolide prodrugs |
| CA2448795A1 (en) * | 2001-03-15 | 2002-09-26 | Pharmagenesis, Inc. | Amino acid derivatives of triptolide compounds as immune modulators and anticancer agent |
| WO2003101951A2 (en) * | 2002-05-31 | 2003-12-11 | Pharmagenesis, Inc. | Triptolide derivatives for modulation of apoptosis and immunosuppression |
| CN100398544C (zh) * | 2002-09-18 | 2008-07-02 | 成都达远药物有限公司 | 高免疫抑制活性的水溶性雷公藤内酯醇衍生物及其应用 |
| JP2006513209A (ja) * | 2002-12-17 | 2006-04-20 | ファーマジェネシス， インコーポレイテッド | 免疫調節因子および抗癌剤としてのトリプトライド誘導体 |
| CN1223595C (zh) * | 2002-12-27 | 2005-10-19 | 中国科学院上海药物研究所 | 雷公藤内酯醇衍生物及其应用 |
| US6943259B2 (en) * | 2003-02-25 | 2005-09-13 | Pharmagenesis, Inc. | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| CN100408583C (zh) * | 2003-02-25 | 2008-08-06 | 美国泛华医药公司 | 用作免疫调节剂和抗癌药的卤代雷公藤内酯醇衍生物 |
| US7820834B2 (en) * | 2003-12-24 | 2010-10-26 | Pharmagenesis, Inc. | Triptolide 5,6-derivatives as immunomodulators and anticancer agents |
| CN1917893A (zh) * | 2004-02-09 | 2007-02-21 | 美国泛华医药公司 | 从雷公藤多苷中分离雷公藤内酯醇化合物的方法 |
| US7863464B2 (en) | 2004-03-02 | 2011-01-04 | Pharmagenesis, Inc. | Triptolide lactone ring derivatives as immunomodulators and anticancer agents |
| WO2006012204A2 (en) * | 2004-06-25 | 2006-02-02 | Pharmagenesis, Inc. | Method for treatment of inflammatory disorders using triptolide compounds |
| US8617906B2 (en) | 2004-10-13 | 2013-12-31 | Pharmagenesis, Inc. | Identification and screening of triptolide target molecules |
| WO2007009055A2 (en) | 2005-07-13 | 2007-01-18 | Salvia Sciences, Inc. | Ester prodrugs of prostratin and related phorbol compounds |
| US9259426B2 (en) | 2006-07-20 | 2016-02-16 | Gilead Sciences, Inc. | 4,6-di- and 2,4,6-trisubstituted quinazoline derivatives useful for treating viral infections |
| WO2008009079A2 (en) | 2006-07-20 | 2008-01-24 | Gilead Sciences, Inc. | Substituted pteridines useful for the treatment and prevention of viral infections |
| US8067632B2 (en) | 2007-07-26 | 2011-11-29 | The Board Of Trustees Of The Leland Stanford Junior University | Process to produce prostratin and structural or functional analogs thereof |
| CN101235041B (zh) * | 2007-10-26 | 2013-05-29 | 北京美迪克斯生物技术有限公司 | 四种雷公藤甲素衍生物及其制剂的制备方法 |
| WO2010091193A2 (en) * | 2009-02-05 | 2010-08-12 | Pharmagenesis, Inc. | Triptolide c-ring derivatives as anticancer agents and immune modulators |
| US9150600B2 (en) | 2009-05-07 | 2015-10-06 | Regents Of The University Of Minnesota | Triptolide prodrugs |
| PL2427467T3 (pl) | 2009-05-07 | 2016-04-29 | Univ Minnesota | Proleki tryptolidu |
| CN102286065B (zh) * | 2010-06-18 | 2012-11-14 | 中国科学院上海药物研究所 | 松香烷型二萜衍生物、其制备方法和应用 |
| RS58781B1 (sr) | 2012-08-23 | 2019-06-28 | Senestech Inc | Kompozicije i postupci za redukciju reproduktivnog kapaciteta ženki pacova |
| AU2016216673B2 (en) | 2015-03-04 | 2017-02-02 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| WO2016205539A1 (en) * | 2015-06-16 | 2016-12-22 | Board Of Regents Of The Nevada System Of Higher Education, On Behalf Of The University Of Nevada, Reno | Non-hormonal male contraceptive agents and methods using same |
| KR102452412B1 (ko) * | 2015-10-29 | 2022-10-06 | 항조우 웨벤 파마슈티컬스 인크 | 트리프톨리드의 c14-히드록실 에스테르화 아미노산 유도체, 및 그의 제조 방법 및 용도 |
| US10640499B2 (en) | 2016-09-02 | 2020-05-05 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| AU2017318601B2 (en) | 2016-09-02 | 2020-09-03 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| CN106890187A (zh) * | 2017-02-22 | 2017-06-27 | 中山大学附属第三医院 | 雷公藤甲素及其修饰物在抑制b细胞产生抗体中的应用 |
| CN109021061B (zh) * | 2018-09-29 | 2019-07-12 | 郭可点 | 雷公藤甲素靶向前药及其制备方法和应用 |
| TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI751516B (zh) | 2019-04-17 | 2022-01-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI879779B (zh) | 2019-06-28 | 2025-04-11 | 美商基利科學股份有限公司 | 類鐸受體調節劑化合物的製備方法 |
| CN111440185B (zh) * | 2020-03-31 | 2021-05-14 | 中国农业科学院蜜蜂研究所 | 一种半抗原及其在检测雷公藤乙素和雷公藤甲素方面的应用 |
| CN115466269A (zh) * | 2021-06-11 | 2022-12-13 | 复旦大学 | 一种胆碱碳酸酯类前药及其制备方法和应用 |
| CN114478684B (zh) * | 2022-01-21 | 2023-10-31 | 南京中医药大学 | 一类雷公藤甲素前药、其制备方法及其医药用途 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4005108A (en) * | 1973-04-03 | 1977-01-25 | Research Corporation | Novel anti-leukemic diterpenoid triepoxides |
| CA1310009C (en) * | 1984-03-28 | 1992-11-10 | John Mark Braughler | Ester prodrugs of steroids |
| CN1027371C (zh) * | 1989-09-08 | 1995-01-11 | 中国医学科学院皮肤病研究所 | 二萜内酯化合物的合成方法 |
| CN1052860A (zh) * | 1989-12-22 | 1991-07-10 | 中国医学科学院皮肤病研究所 | 雷藤氯内酯醇的制备方法及抗生育用途 |
| US5430054A (en) * | 1989-12-22 | 1995-07-04 | Jiangsu Family Planning Institute | Preparation methods of diterpene lactone compounds and application of the same to antifertility |
| CN1052859A (zh) * | 1989-12-22 | 1991-07-10 | 中国医学科学院皮肤病研究所 | 17-羟基雷藤内酯醇及类似物的结构与制备方法 |
| CN1052861A (zh) * | 1989-12-22 | 1991-07-10 | 中国医学科学院皮肤病研究所 | 雷醇内酯的制备方法及抗生育用途 |
| AU7570191A (en) * | 1990-03-14 | 1991-10-10 | Board Of Regents, The University Of Texas System | Tripterygium wilfordii hook f extracts and components thereof for immunosuppression |
-
1996
- 1996-03-01 US US08/609,277 patent/US5663335A/en not_active Expired - Lifetime
-
1997
- 1997-02-18 WO PCT/US1997/002331 patent/WO1997031920A1/en not_active Ceased
- 1997-02-18 AU AU21258/97A patent/AU2125897A/en not_active Abandoned
- 1997-02-28 DK DK97908794T patent/DK0907652T3/da active
- 1997-02-28 AU AU20613/97A patent/AU712241B2/en not_active Ceased
- 1997-02-28 CN CNB971942471A patent/CN1133637C/zh not_active Expired - Fee Related
- 1997-02-28 JP JP53117297A patent/JP4267697B2/ja not_active Expired - Fee Related
- 1997-02-28 CA CA002248266A patent/CA2248266C/en not_active Expired - Fee Related
- 1997-02-28 EP EP97908794A patent/EP0907652B1/en not_active Expired - Lifetime
- 1997-02-28 AT AT97908794T patent/ATE296304T1/de not_active IP Right Cessation
- 1997-02-28 PT PT97908794T patent/PT907652E/pt unknown
- 1997-02-28 WO PCT/US1997/003202 patent/WO1997031921A1/en not_active Ceased
- 1997-02-28 ES ES97908794T patent/ES2242214T3/es not_active Expired - Lifetime
- 1997-02-28 DE DE69733353T patent/DE69733353T2/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0907652A1 (en) | 1999-04-14 |
| AU712241B2 (en) | 1999-11-04 |
| PT907652E (pt) | 2005-08-31 |
| ATE296304T1 (de) | 2005-06-15 |
| AU2061397A (en) | 1997-09-16 |
| DE69733353T2 (de) | 2006-02-02 |
| CN1246121A (zh) | 2000-03-01 |
| AU2125897A (en) | 1997-09-16 |
| CA2248266C (en) | 2007-10-23 |
| DK0907652T3 (da) | 2005-08-08 |
| WO1997031921A1 (en) | 1997-09-04 |
| DE69733353D1 (de) | 2005-06-30 |
| US5663335A (en) | 1997-09-02 |
| WO1997031920A1 (en) | 1997-09-04 |
| HK1019444A1 (en) | 2000-02-11 |
| JP2001504437A (ja) | 2001-04-03 |
| CA2248266A1 (en) | 1997-09-04 |
| CN1133637C (zh) | 2004-01-07 |
| JP4267697B2 (ja) | 2009-05-27 |
| EP0907652B1 (en) | 2005-05-25 |
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