CA2626032C - Camptothecin derivatives as chemoradiosensitizing agents - Google Patents
Camptothecin derivatives as chemoradiosensitizing agents Download PDFInfo
- Publication number
- CA2626032C CA2626032C CA2626032A CA2626032A CA2626032C CA 2626032 C CA2626032 C CA 2626032C CA 2626032 A CA2626032 A CA 2626032A CA 2626032 A CA2626032 A CA 2626032A CA 2626032 C CA2626032 C CA 2626032C
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- Prior art keywords
- lower alkyl
- alkyl
- amino
- hydroxy
- substituted
- Prior art date
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- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 title claims abstract description 383
- 229940127093 camptothecin Drugs 0.000 claims abstract description 609
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims abstract description 591
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims abstract description 589
- 150000001875 compounds Chemical class 0.000 claims abstract description 218
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 109
- 230000005855 radiation Effects 0.000 claims abstract description 62
- 201000011510 cancer Diseases 0.000 claims abstract description 53
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 208000035269 cancer or benign tumor Diseases 0.000 claims abstract description 24
- -1 nitro-substituted phenyl Chemical group 0.000 claims description 476
- 125000000217 alkyl group Chemical group 0.000 claims description 405
- 125000003545 alkoxy group Chemical group 0.000 claims description 263
- 229910052739 hydrogen Inorganic materials 0.000 claims description 156
- 239000001257 hydrogen Substances 0.000 claims description 153
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 109
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 107
- 150000002431 hydrogen Chemical group 0.000 claims description 105
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 103
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 100
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 80
- 235000000346 sugar Nutrition 0.000 claims description 78
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 72
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 70
- 125000000623 heterocyclic group Chemical group 0.000 claims description 66
- 125000001424 substituent group Chemical group 0.000 claims description 50
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 44
- 125000004414 alkyl thio group Chemical group 0.000 claims description 42
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 41
- 125000002837 carbocyclic group Chemical group 0.000 claims description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 35
- 210000004881 tumor cell Anatomy 0.000 claims description 34
- 229910052717 sulfur Inorganic materials 0.000 claims description 32
- 125000003282 alkyl amino group Chemical group 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 30
- SNLFYGIUTYKKOE-UHFFFAOYSA-N 4-n,4-n-bis(4-aminophenyl)benzene-1,4-diamine Chemical compound C1=CC(N)=CC=C1N(C=1C=CC(N)=CC=1)C1=CC=C(N)C=C1 SNLFYGIUTYKKOE-UHFFFAOYSA-N 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- 125000003118 aryl group Chemical class 0.000 claims description 27
- 125000002947 alkylene group Chemical group 0.000 claims description 26
- 230000000637 radiosensitizating effect Effects 0.000 claims description 26
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- MENHXVNCWVKFRA-UHFFFAOYSA-N 1,4-oxazin-2-one Chemical group O=C1C=NC=CO1 MENHXVNCWVKFRA-UHFFFAOYSA-N 0.000 claims description 16
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical group C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 claims description 16
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 16
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 16
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 16
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 15
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 15
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 15
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 15
- 229920002554 vinyl polymer Polymers 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 12
- 150000002367 halogens Chemical group 0.000 claims description 12
- 230000001235 sensitizing effect Effects 0.000 claims description 12
- 229960000583 acetic acid Drugs 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- MSBZUOIIUNSSRF-UHFFFAOYSA-N 1-oxido-1,2,3-benzotriazin-1-ium Chemical class C1=CC=C2[N+]([O-])=NN=CC2=C1 MSBZUOIIUNSSRF-UHFFFAOYSA-N 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 229930192474 thiophene Natural products 0.000 claims description 9
- 150000003852 triazoles Chemical class 0.000 claims description 9
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 7
- 230000002195 synergetic effect Effects 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- MQTMHRXULFJFOC-UHFFFAOYSA-N 2-[(2,4,5,7-tetranitrofluoren-9-ylidene)amino]oxypropanoic acid Chemical group C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1C(=NOC(C)C(O)=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C12 MQTMHRXULFJFOC-UHFFFAOYSA-N 0.000 claims description 6
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 6
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
- UJKDDHMBQYSTLZ-UHFFFAOYSA-N 2-[(2,4,5,7-tetranitrofluoren-9-ylidene)amino]oxyacetic acid Chemical group C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1C(=NOCC(=O)O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C12 UJKDDHMBQYSTLZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 229940054066 benzamide antipsychotics Drugs 0.000 claims description 3
- 150000003936 benzamides Chemical class 0.000 claims description 3
- 150000002240 furans Chemical class 0.000 claims description 3
- 150000002460 imidazoles Chemical class 0.000 claims description 3
- 235000005152 nicotinamide Nutrition 0.000 claims description 3
- 150000005480 nicotinamides Chemical class 0.000 claims description 3
- 150000002916 oxazoles Chemical class 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 150000003222 pyridines Chemical class 0.000 claims description 3
- 150000003577 thiophenes Chemical class 0.000 claims description 3
- VMWJCFLUSKZZDX-UHFFFAOYSA-N n,n-dimethylmethanamine Chemical group [CH2]N(C)C VMWJCFLUSKZZDX-UHFFFAOYSA-N 0.000 claims description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 68
- 125000001475 halogen functional group Chemical group 0.000 claims 46
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 7
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 2
- 238000001959 radiotherapy Methods 0.000 abstract description 24
- 239000000941 radioactive substance Substances 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 103
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 82
- 210000004027 cell Anatomy 0.000 description 60
- 125000005843 halogen group Chemical group 0.000 description 59
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- 239000000243 solution Substances 0.000 description 55
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 44
- 238000000034 method Methods 0.000 description 44
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 38
- 239000002502 liposome Substances 0.000 description 38
- 150000003254 radicals Chemical group 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
- 229920006395 saturated elastomer Polymers 0.000 description 33
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- JOERSAVCLPYNIZ-UHFFFAOYSA-N 2,4,5,7-tetranitrofluoren-9-one Chemical compound O=C1C2=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C2C2=C1C=C([N+](=O)[O-])C=C2[N+]([O-])=O JOERSAVCLPYNIZ-UHFFFAOYSA-N 0.000 description 29
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
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- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 19
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
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| US72892405P | 2005-10-21 | 2005-10-21 | |
| US60/728,924 | 2005-10-21 | ||
| US11/444,150 | 2006-05-30 | ||
| US11/444,150 US7875602B2 (en) | 2005-10-21 | 2006-05-30 | Camptothecin derivatives as chemoradiosensitizing agents |
| PCT/US2006/041175 WO2007048002A2 (en) | 2005-10-21 | 2006-10-19 | Camptothecin derivatives as chemoradiosensitizing agents |
Publications (2)
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| CA2626032A1 CA2626032A1 (en) | 2007-04-26 |
| CA2626032C true CA2626032C (en) | 2011-12-06 |
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| CA2626032A Active CA2626032C (en) | 2005-10-21 | 2006-10-19 | Camptothecin derivatives as chemoradiosensitizing agents |
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| EP (1) | EP1951231B1 (enExample) |
| JP (1) | JP5328357B2 (enExample) |
| KR (1) | KR101320160B1 (enExample) |
| CN (1) | CN101300009B (enExample) |
| AU (1) | AU2006304811C1 (enExample) |
| CA (1) | CA2626032C (enExample) |
| ES (1) | ES2428088T3 (enExample) |
| NZ (2) | NZ593706A (enExample) |
| TW (1) | TWI402270B (enExample) |
| WO (1) | WO2007048002A2 (enExample) |
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| CN101402640B (zh) * | 2008-09-02 | 2011-06-15 | 暨南大学 | 双酯化喜树碱衍生物及其制备方法和应用 |
| DE102009004204A1 (de) * | 2009-01-09 | 2010-07-15 | Christian-Albrechts-Universität Zu Kiel | Verfahren zur verbesserten Bioaktivierung von Arzneistoffen |
| US8168648B2 (en) * | 2009-03-06 | 2012-05-01 | Taiwan Liposome Co., Ltd. | Camptothecin derivatives and uses thereof |
| US8575188B2 (en) | 2009-06-17 | 2013-11-05 | Threshold Pharmaceuticals, Inc. | Camptothecin derivatives |
| US10391056B2 (en) | 2011-11-03 | 2019-08-27 | Taiwan Lipsome Company, LTD. | Pharmaceutical compositions of hydrophobic camptothecin derivatives |
| US10980798B2 (en) | 2011-11-03 | 2021-04-20 | Taiwan Liposome Company, Ltd. | Pharmaceutical compositions of hydrophobic camptothecin derivatives |
| US20140135357A1 (en) * | 2012-11-12 | 2014-05-15 | Taiwan Liposome Company, Ltd. | Dose regime for camptothecin derivatives |
| AU2014216178B2 (en) | 2013-02-15 | 2018-06-28 | KALA BIO, Inc. | Therapeutic compounds and uses thereof |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| EP2958895B1 (en) | 2013-02-20 | 2020-08-19 | Kala Pharmaceuticals, Inc. | Therapeutic compounds and uses thereof |
| US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| CA2928658A1 (en) | 2013-11-01 | 2015-05-07 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| WO2015098963A1 (ja) | 2013-12-26 | 2015-07-02 | 東亞合成株式会社 | カルレティキュリンの発現促進方法および該方法に用いられる合成ペプチド |
| JP6872713B2 (ja) | 2015-05-29 | 2021-05-19 | 東亞合成株式会社 | 腫瘍細胞の放射線感受性を増大させる合成ペプチド及びその利用 |
| US10087194B2 (en) | 2015-10-27 | 2018-10-02 | California Pacific Medical Center | Podophyllotoxin derivatives and their use |
| ES2806624T3 (es) | 2015-10-27 | 2021-02-18 | California Pacific Medical Center | Derivados de podofilotoxina y su uso |
| AU2017324713B2 (en) | 2016-09-08 | 2020-08-13 | KALA BIO, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| CA3036340A1 (en) | 2016-09-08 | 2018-03-15 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| CA3036065A1 (en) | 2016-09-08 | 2018-03-15 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| CN114341141A (zh) | 2019-07-11 | 2022-04-12 | 太阳医药高级研究有限公司 | 具有二硫部分和哌嗪部分的喜树碱衍生物 |
| JP2023512214A (ja) | 2020-01-28 | 2023-03-24 | リフレクション メディカル， インコーポレイテッド | 放射性核種および外部ビーム放射線療法の共同最適化 |
Family Cites Families (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US554990A (en) * | 1896-02-18 | Target-throwing trap | ||
| US4399282A (en) | 1979-07-10 | 1983-08-16 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives |
| JPS6019790A (ja) | 1983-07-14 | 1985-01-31 | Yakult Honsha Co Ltd | 新規なカンプトテシン誘導体 |
| US5196413A (en) | 1984-12-10 | 1993-03-23 | Johnson Matthey, Inc. | Platinum complexes and the like |
| US4663161A (en) | 1985-04-22 | 1987-05-05 | Mannino Raphael J | Liposome methods and compositions |
| US5032617A (en) | 1985-05-03 | 1991-07-16 | Sri International | Substituted benzamide radiosensitizers |
| US5041653A (en) | 1985-05-03 | 1991-08-20 | Sri International | Substituted benzamide radiosensitizers |
| US5175278A (en) | 1985-06-28 | 1992-12-29 | Merck & Co., Inc. | Heteropolysaccharide S-657 |
| US4727068A (en) | 1985-10-23 | 1988-02-23 | Johnson Matthey, Inc. | Radiosensitization by cobalt and Fe(III) complexes |
| US5175287A (en) | 1986-09-25 | 1992-12-29 | S R I International | Process for preparing 1,2,4-benzotriazine oxides |
| US5026694A (en) | 1987-04-13 | 1991-06-25 | The British Columbia Cancer Foundation | Platinum complexes with one radiosensitizing ligand |
| US4921963A (en) | 1987-04-13 | 1990-05-01 | British Columbia Cancer Foundation | Platinum complexes with one radiosensitizing ligand |
| CA1329206C (en) | 1987-06-10 | 1994-05-03 | Tsutomu Kagiya | Fluorine-containing nitroazole derivatives and radiosensitizer comprising the same |
| US5304654A (en) | 1987-06-10 | 1994-04-19 | Yasunori Nishijima | Fluorine-containing nitroimidazole compounds |
| US4797397A (en) | 1987-07-31 | 1989-01-10 | Warner-Lambert Company | 2-nitroimidazole derivatives useful as radiosensitizers for hypoxic tumor cells |
| US4943579A (en) | 1987-10-06 | 1990-07-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Water soluble prodrugs of camptothecin |
| JPH0819111B2 (ja) | 1987-10-22 | 1996-02-28 | ポーラ化成工業株式会社 | ２―ニトロイミダゾール誘導体及びこれを有効成分とする放射線増感剤 |
| US5036096A (en) | 1988-11-25 | 1991-07-30 | Warner-Lambert Company | Aziridino derivatives of nitroimidazoles and pharmaceutical compositions of selected derivatives |
| US4954515A (en) | 1988-11-25 | 1990-09-04 | Warner-Lambert Company | Haloalkylaminomethyl-2-nitro-1H-imidazoles |
| US5043165A (en) | 1988-12-14 | 1991-08-27 | Liposome Technology, Inc. | Novel liposome composition for sustained release of steroidal drugs |
| IL92597A0 (en) | 1988-12-14 | 1990-08-31 | Yasunori Nishijima President K | Novel fluorine-containing 2-nitroimidazole derivatives and radiosensitizer comprising the same |
| US5077057A (en) | 1989-04-05 | 1991-12-31 | The Regents Of The University Of California | Preparation of liposome and lipid complex compositions |
| US5549910A (en) | 1989-03-31 | 1996-08-27 | The Regents Of The University Of California | Preparation of liposome and lipid complex compositions |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5294715A (en) | 1991-02-01 | 1994-03-15 | University Of Pittsburgh | Acridine-intercalator based hypoxia selective cytotoxins |
| CA2097163C (en) | 1992-06-01 | 2002-07-30 | Marianna Foldvari | Topical patch for liposomal drug delivery system |
| MX9304399A (es) | 1992-07-31 | 1994-02-28 | Warner Lambert Co | Proceso novedoso para preparar [[2-bromoetil)-amino]metil]-2-nitro-1h-imidazol-1-etanol quiral y compuestos relacionados. |
| US5552156A (en) | 1992-10-23 | 1996-09-03 | Ohio State University | Liposomal and micellular stabilization of camptothecin drugs |
| US5631237A (en) | 1992-12-22 | 1997-05-20 | Dzau; Victor J. | Method for producing in vivo delivery of therapeutic agents via liposomes |
| GB9320781D0 (en) | 1993-10-08 | 1993-12-01 | Erba Carlo Spa | Polymer-bound camptothecin derivatives |
| US5965566A (en) | 1993-10-20 | 1999-10-12 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
| US5919455A (en) | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5646159A (en) | 1994-07-20 | 1997-07-08 | Research Triangle Institute | Water-soluble esters of camptothecin compounds |
| GB9504065D0 (en) | 1995-03-01 | 1995-04-19 | Pharmacia Spa | Poly-pyrrolecarboxamidonaphthalenic acid derivatives |
| US5736156A (en) | 1995-03-22 | 1998-04-07 | The Ohio State University | Liposomal anf micellular stabilization of camptothecin drugs |
| US6060604A (en) | 1995-03-31 | 2000-05-09 | Florida State University | Pharmaceutical compounds comprising polyamines substituted with electron-affinic groups |
| JPH08333370A (ja) | 1995-06-08 | 1996-12-17 | Kyorin Pharmaceut Co Ltd | 水に可溶な新規フルオロエチルカンプトテシン誘導体、及びその製造方法 |
| US6339091B1 (en) | 1995-06-21 | 2002-01-15 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Comptothecin analogues, preparation methods therefor, use thereof as drugs, and pharmaceutical compositions containing said analogues |
| GB9512670D0 (en) | 1995-06-21 | 1995-08-23 | Sod Conseils Rech Applic | Camptothecin analogues |
| CN1211919A (zh) | 1995-09-13 | 1999-03-24 | 佛罗里达州立大学 | 放射增敏性紫杉烷及其药物制剂 |
| WO1997019085A1 (en) | 1995-11-22 | 1997-05-29 | Research Triangle Institute | Camptothecin compounds with combined topoisomerase i inhibition and dna alkylation properties |
| US6096336A (en) | 1996-01-30 | 2000-08-01 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
| US5731316A (en) | 1996-01-30 | 1998-03-24 | The Stehlin Foundation For Cancer Research | Derivatives of camptothecin and methods of treating cancer using these derivatives |
| US5874105A (en) | 1996-01-31 | 1999-02-23 | Collaborative Laboratories, Inc. | Lipid vesicles formed with alkylammonium fatty acid salts |
| ATE261974T1 (de) | 1996-08-19 | 2004-04-15 | Bionumerik Pharmaceuticals Inc | Hoch-lipophile campothecin-derivate |
| AU4424797A (en) | 1996-09-18 | 1998-04-14 | Dragoco Inc. | Liposome encapsulated active agent dry powder composition |
| AU739028B2 (en) | 1996-09-27 | 2001-10-04 | Bristol-Myers Squibb Company | Hydrolyzable prodrugs for delivery of anticancer drugs to metastatic cells |
| ATE210673T1 (de) | 1996-09-30 | 2001-12-15 | Bayer Ag | Glycokonjugate von modifizierten camptothecin- derivaten (20-o-verknüpfung) |
| KR100219562B1 (ko) * | 1996-10-28 | 1999-09-01 | 윤종용 | 반도체장치의 다층 배선 형성방법 |
| SG104284A1 (en) | 1996-10-30 | 2004-06-21 | Tanabe Seiyaku Co | S type 2-substituted hydroxy-2-indolidinylbutyric ester compounds and process for preparation thereof |
| US5827533A (en) | 1997-02-06 | 1998-10-27 | Duke University | Liposomes containing active agents aggregated with lipid surfactants |
| ES2262223T3 (es) | 1997-02-14 | 2006-11-16 | Bionumerik Pharmaceuticals, Inc. | Derivados de camptotecina altamente lipofilos. |
| JP3209509B2 (ja) * | 1997-03-28 | 2001-09-17 | インターナショナル・ビジネス・マシーンズ・コーポレーション | ディスク状記録装置及びディスクドライブ装置 |
| ID23424A (id) | 1997-05-14 | 2000-04-20 | Bayer Ag | Glikokonjugat dari 20(s)-kamptotesin |
| GB9721070D0 (en) | 1997-10-03 | 1997-12-03 | Pharmacia & Upjohn Spa | Bioactive derivatives of camptothecin |
| US5935949A (en) | 1998-03-20 | 1999-08-10 | Trustees Of Dartmouth College | Use of androgen therapy in fibromyalgia and chronic fatigue syndrome |
| US6153655A (en) | 1998-04-17 | 2000-11-28 | Enzon, Inc. | Terminally-branched polymeric linkers and polymeric conjugates containing the same |
| US6057303A (en) | 1998-10-20 | 2000-05-02 | Bionumerik Pharmaceuticals, Inc. | Highly lipophilic Camptothecin derivatives |
| US6207832B1 (en) | 1999-04-09 | 2001-03-27 | University Of Pittsburgh | Camptothecin analogs and methods of preparation thereof |
| US6281223B1 (en) | 1999-04-13 | 2001-08-28 | Supergen, Inc. | Radioenhanced camptothecin derivative cancer treatments |
| WO2000066127A1 (en) | 1999-05-04 | 2000-11-09 | Bionumerik Pharmaceuticals, Inc. | Novel highly lipophilic camptothecin analogs |
| US6765019B1 (en) | 1999-05-06 | 2004-07-20 | University Of Kentucky Research Foundation | Permeable, water soluble, non-irritating prodrugs of chemotherapeutic agents with oxaalkanoic acids |
| US6228855B1 (en) * | 1999-08-03 | 2001-05-08 | The Stehlin Foundation For Cancer Research | Aromatic esters of camptothecins and methods to treat cancers |
| CA2391534A1 (en) * | 1999-11-15 | 2001-05-25 | Drug Innovation & Design, Inc. | Selective cellular targeting: multifunctional delivery vehicles |
| US6423707B1 (en) | 2000-08-28 | 2002-07-23 | California Pacific Medical Center | Nitroimidazole ester analogues and therapeutic applications |
| US6350756B1 (en) | 2001-01-18 | 2002-02-26 | California Pacific Medical Center | Camptothecin derivatives |
| US6855720B2 (en) | 2001-03-01 | 2005-02-15 | California Pacific Medical Center | Nitrogen-based camptothecin derivatives |
| US6403604B1 (en) | 2001-03-01 | 2002-06-11 | California Pacific Medical Center | Nitrogen-based camptothecin derivatives |
| GB0119578D0 (en) | 2001-08-10 | 2001-10-03 | Pharmacia & Upjohn Spa | Fluoro linkers |
| AU2003243380A1 (en) | 2002-06-03 | 2003-12-19 | California Pacific Medical Center | Nitrogen-based homo-camptothecin derivatives |
-
2006
- 2006-05-30 US US11/444,150 patent/US7875602B2/en active Active
- 2006-10-19 WO PCT/US2006/041175 patent/WO2007048002A2/en not_active Ceased
- 2006-10-19 CN CN2006800390612A patent/CN101300009B/zh not_active Expired - Fee Related
- 2006-10-19 ES ES06836448T patent/ES2428088T3/es active Active
- 2006-10-19 KR KR1020087012095A patent/KR101320160B1/ko not_active Expired - Fee Related
- 2006-10-19 AU AU2006304811A patent/AU2006304811C1/en not_active Ceased
- 2006-10-19 NZ NZ593706A patent/NZ593706A/xx not_active IP Right Cessation
- 2006-10-19 JP JP2008536850A patent/JP5328357B2/ja not_active Expired - Fee Related
- 2006-10-19 CA CA2626032A patent/CA2626032C/en active Active
- 2006-10-19 NZ NZ567454A patent/NZ567454A/en not_active IP Right Cessation
- 2006-10-19 EP EP06836448.8A patent/EP1951231B1/en active Active
- 2006-10-20 TW TW095138924A patent/TWI402270B/zh not_active IP Right Cessation
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2008
- 2008-07-29 US US12/124,712 patent/US8563537B2/en not_active Expired - Fee Related
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2011
- 2011-01-24 US US13/012,772 patent/US8779138B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2006304811C1 (en) | 2012-11-01 |
| NZ593706A (en) | 2012-11-30 |
| TWI402270B (zh) | 2013-07-21 |
| NZ567454A (en) | 2011-07-29 |
| US20110184009A1 (en) | 2011-07-28 |
| JP5328357B2 (ja) | 2013-10-30 |
| TW200730532A (en) | 2007-08-16 |
| AU2006304811B2 (en) | 2012-03-22 |
| WO2007048002A2 (en) | 2007-04-26 |
| US7875602B2 (en) | 2011-01-25 |
| WO2007048002A3 (en) | 2007-09-13 |
| EP1951231A4 (en) | 2010-09-22 |
| JP2009512714A (ja) | 2009-03-26 |
| US8563537B2 (en) | 2013-10-22 |
| CA2626032A1 (en) | 2007-04-26 |
| ES2428088T3 (es) | 2013-11-05 |
| KR101320160B1 (ko) | 2013-10-23 |
| EP1951231A2 (en) | 2008-08-06 |
| US8779138B2 (en) | 2014-07-15 |
| HK1115321A1 (en) | 2008-11-28 |
| AU2006304811A1 (en) | 2007-04-26 |
| US20070093432A1 (en) | 2007-04-26 |
| EP1951231B1 (en) | 2013-07-31 |
| CN101300009A (zh) | 2008-11-05 |
| KR20080086436A (ko) | 2008-09-25 |
| US20080318873A1 (en) | 2008-12-25 |
| CN101300009B (zh) | 2013-04-03 |
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