AU2002237884B2 - Anticancer treatment using triptolide prodrugs - Google Patents
Anticancer treatment using triptolide prodrugs Download PDFInfo
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- AU2002237884B2 AU2002237884B2 AU2002237884A AU2002237884A AU2002237884B2 AU 2002237884 B2 AU2002237884 B2 AU 2002237884B2 AU 2002237884 A AU2002237884 A AU 2002237884A AU 2002237884 A AU2002237884 A AU 2002237884A AU 2002237884 B2 AU2002237884 B2 AU 2002237884B2
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- alkyl
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- DFBIRQPKNDILPW-CIVMWXNOSA-N Triptolide Chemical compound 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 title claims abstract description 48
- YKUJZZHGTWVWHA-UHFFFAOYSA-N triptolide Natural products COC12CC3OC3(C(C)C)C(O)C14OC4CC5C6=C(CCC25C)C(=O)OC6 YKUJZZHGTWVWHA-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 229940002612 prodrug Drugs 0.000 title claims abstract description 30
- 239000000651 prodrug Substances 0.000 title claims abstract description 30
- 238000011394 anticancer treatment Methods 0.000 title claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
- 238000011282 treatment Methods 0.000 claims description 36
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 28
- 125000006413 ring segment Chemical group 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 26
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 24
- -1 fluoroalkyl sulfonate Chemical compound 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 239000001301 oxygen Substances 0.000 claims description 24
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 229910002651 NO3 Inorganic materials 0.000 claims description 13
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 13
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- 239000005864 Sulphur Substances 0.000 claims description 12
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- 125000003545 alkoxy group Chemical group 0.000 claims description 10
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 239000010452 phosphate Substances 0.000 claims description 10
- 229920000570 polyether Polymers 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
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- UQSQSQZYBQSBJZ-UHFFFAOYSA-M fluorosulfonate Chemical compound [O-]S(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-M 0.000 claims description 8
- 150000001768 cations Chemical class 0.000 claims description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
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- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 5
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- 229910052698 phosphorus Inorganic materials 0.000 claims description 5
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- 206010006187 Breast cancer Diseases 0.000 claims description 4
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- IWYVYUZADLIDEY-UHFFFAOYSA-N 4-methoxybenzenesulfonic acid Chemical compound COC1=CC=C(S(O)(=O)=O)C=C1 IWYVYUZADLIDEY-UHFFFAOYSA-N 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 3
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- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
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- 208000020816 lung neoplasm Diseases 0.000 claims 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 2
- 240000007594 Oryza sativa Species 0.000 claims 1
- 235000007164 Oryza sativa Nutrition 0.000 claims 1
- 235000009566 rice Nutrition 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 35
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 abstract description 12
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- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002246 antineoplastic agent Substances 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract description 3
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- 229940127089 cytotoxic agent Drugs 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 37
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- HROMYAWHLUOUPY-AHCCQAQQSA-N omtriptolide Chemical compound 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 HROMYAWHLUOUPY-AHCCQAQQSA-N 0.000 description 13
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
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- Health & Medical Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/766,156 US6620843B2 (en) | 2001-01-19 | 2001-01-19 | Anticancer treatment using triptolide prodrugs |
| US09/766,156 | 2001-01-19 | ||
| PCT/US2002/001650 WO2002056835A2 (en) | 2001-01-19 | 2002-01-18 | Anticancer treatment using triptolide prodrugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002237884A1 AU2002237884A1 (en) | 2003-02-13 |
| AU2002237884B2 true AU2002237884B2 (en) | 2006-08-17 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002237884A Ceased AU2002237884B2 (en) | 2001-01-19 | 2002-01-18 | Anticancer treatment using triptolide prodrugs |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6620843B2 (enExample) |
| EP (1) | EP1359909B1 (enExample) |
| JP (1) | JP2004517882A (enExample) |
| AT (1) | ATE406155T1 (enExample) |
| AU (1) | AU2002237884B2 (enExample) |
| CA (1) | CA2435322A1 (enExample) |
| DE (1) | DE60228544D1 (enExample) |
| WO (1) | WO2002056835A2 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2485794C (en) * | 2002-05-31 | 2012-10-16 | 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 |
| WO2004058246A1 (en) * | 2002-12-17 | 2004-07-15 | Pharmagenesis, Inc. | Triptolide derivatives as immunomodulator and anticancer agents |
| US6943259B2 (en) * | 2003-02-25 | 2005-09-13 | Pharmagenesis, Inc. | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| WO2005062913A2 (en) * | 2003-12-24 | 2005-07-14 | Pharmagenesis, Inc. | Triplide 5,6-derivatives as immunomodulators and anticancer agents |
| WO2005077008A2 (en) * | 2004-02-09 | 2005-08-25 | Pharmagenesis, Inc. | Methods for isolation of triptolide compounds from tripterygium wilfordii |
| AU2005218610B2 (en) * | 2004-03-02 | 2011-08-18 | Pharmagenesis, Inc. | Triptolide lactone ring derivatives as immunomodulators and anticancer agents |
| US20070244080A1 (en) * | 2004-06-25 | 2007-10-18 | 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 |
| EP1946758A1 (en) * | 2007-01-18 | 2008-07-23 | Pierre Fabre Medicament | Treatment of acute myeloid leukemia |
| US20100087337A1 (en) * | 2008-09-10 | 2010-04-08 | Bind Biosciences, Inc. | High Throughput Fabrication of Nanoparticles |
| EP2393818A4 (en) * | 2009-02-05 | 2013-09-04 | Pharmagenesis Inc | TRIPTOLID C-RING DERIVATIVES AS ANTITUMULAR AGENTS AND IMMUNOMODULATORS |
| PL2427467T3 (pl) * | 2009-05-07 | 2016-04-29 | Univ Minnesota | Proleki tryptolidu |
| US9150600B2 (en) | 2009-05-07 | 2015-10-06 | Regents Of The University Of Minnesota | Triptolide prodrugs |
| WO2011127291A2 (en) * | 2010-04-07 | 2011-10-13 | Caritas St. Elizabeth Medical Center Of Boston, Inc. | Compositions and methods for the treatment of a neoplasia |
| WO2013130603A1 (en) | 2012-02-27 | 2013-09-06 | Board Of Regents, The University Of Texas System | Ganglioside gd2 as a marker and target on cancer stem cells |
| WO2017136739A1 (en) * | 2016-02-04 | 2017-08-10 | The Johns Hopkins University | Glucose conjugates of triptolide, analogs and uses thereof |
| CN107698653B (zh) * | 2017-10-11 | 2019-08-27 | 中国农业科学院蜜蜂研究所 | 一种雷公藤甲素半抗原及其制备方法与应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU7093700A (en) * | 1999-08-30 | 2001-03-26 | Board Of Trustees Of The Leland Stanford Junior University | Uses of diterpenoid triepoxides as an anti-proliferative agent |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4005108A (en) | 1973-04-03 | 1977-01-25 | Research Corporation | Novel anti-leukemic diterpenoid triepoxides |
| US5919816A (en) * | 1994-11-14 | 1999-07-06 | Bionumerik Pharmaceuticals, Inc. | Formulations and methods of reducing toxicity of antineoplastic agents |
| US5663335A (en) * | 1996-03-01 | 1997-09-02 | Pharmagenesis, Inc. | Immunosuppressive compounds and methods |
| US5962516A (en) | 1997-02-28 | 1999-10-05 | Pharmagenesis, Inc. | Immunosuppressive compounds and methods |
| US6548537B1 (en) * | 1998-09-02 | 2003-04-15 | Pharmagenesis, Inc. | Triptolide prodrugs having high aqueous solubility |
| AU764123B2 (en) * | 1998-09-02 | 2003-08-07 | Pharmagenesis, Inc. | Triptolide prodrugs having high aqueous solubility |
| EP1390358A4 (en) * | 2001-03-15 | 2004-06-16 | Pharmagenesis Inc | AMINO ACID DERIVATIVES OF TRIPTOLIDE COMPOUNDS AS IMMUNOMODULATORS AND ANTICROPHES |
-
2001
- 2001-01-19 US US09/766,156 patent/US6620843B2/en not_active Expired - Fee Related
-
2002
- 2002-01-18 AU AU2002237884A patent/AU2002237884B2/en not_active Ceased
- 2002-01-18 JP JP2002557346A patent/JP2004517882A/ja active Pending
- 2002-01-18 WO PCT/US2002/001650 patent/WO2002056835A2/en not_active Ceased
- 2002-01-18 AT AT02704187T patent/ATE406155T1/de not_active IP Right Cessation
- 2002-01-18 DE DE60228544T patent/DE60228544D1/de not_active Expired - Fee Related
- 2002-01-18 CA CA002435322A patent/CA2435322A1/en not_active Abandoned
- 2002-01-18 EP EP02704187A patent/EP1359909B1/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU7093700A (en) * | 1999-08-30 | 2001-03-26 | Board Of Trustees Of The Leland Stanford Junior University | Uses of diterpenoid triepoxides as an anti-proliferative agent |
Also Published As
| Publication number | Publication date |
|---|---|
| DE60228544D1 (de) | 2008-10-09 |
| US20020099051A1 (en) | 2002-07-25 |
| CA2435322A1 (en) | 2002-07-25 |
| US6620843B2 (en) | 2003-09-16 |
| WO2002056835A3 (en) | 2003-02-27 |
| JP2004517882A (ja) | 2004-06-17 |
| WO2002056835A2 (en) | 2002-07-25 |
| EP1359909B1 (en) | 2008-08-27 |
| EP1359909A4 (en) | 2005-03-09 |
| ATE406155T1 (de) | 2008-09-15 |
| EP1359909A2 (en) | 2003-11-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |