JP2000513716A - タキサン誘導体、その調製、及びそれを含有する処方物 - Google Patents
タキサン誘導体、その調製、及びそれを含有する処方物Info
- Publication number
- JP2000513716A JP2000513716A JP09540444A JP54044497A JP2000513716A JP 2000513716 A JP2000513716 A JP 2000513716A JP 09540444 A JP09540444 A JP 09540444A JP 54044497 A JP54044497 A JP 54044497A JP 2000513716 A JP2000513716 A JP 2000513716A
- Authority
- JP
- Japan
- Prior art keywords
- group
- compound
- hydrogen
- deacetyl
- dehydro
- 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.)
- Granted
Links
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 title abstract description 6
- 238000002360 preparation method Methods 0.000 title abstract description 3
- 239000000203 mixture Substances 0.000 title description 8
- 238000009472 formulation Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 20
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical group NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims abstract description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 229960001592 paclitaxel Drugs 0.000 claims description 6
- 150000005676 cyclic carbonates Chemical class 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 229940127089 cytotoxic agent Drugs 0.000 claims description 3
- 239000002254 cytotoxic agent Substances 0.000 claims description 3
- 230000001472 cytotoxic effect Effects 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
- 229940034982 antineoplastic agent Drugs 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 231100000433 cytotoxic Toxicity 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims 1
- OVMSOCFBDVBLFW-VHLOTGQHSA-N 5beta,20-epoxy-1,7beta,13alpha-trihydroxy-9-oxotax-11-ene-2alpha,4alpha,10beta-triyl 4,10-diacetate 2-benzoate Chemical compound O([C@@H]1[C@@]2(C[C@H](O)C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 abstract description 9
- YWLXLRUDGLRYDR-ZHPRIASZSA-N 5beta,20-epoxy-1,7beta,10beta,13alpha-tetrahydroxy-9-oxotax-11-ene-2alpha,4alpha-diyl 4-acetate 2-benzoate Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 abstract description 8
- 229930014667 baccatin III Natural products 0.000 abstract description 5
- 150000002148 esters Chemical class 0.000 abstract description 3
- 230000006907 apoptotic process Effects 0.000 abstract description 2
- 239000012736 aqueous medium Substances 0.000 abstract description 2
- 229910052799 carbon Inorganic materials 0.000 abstract description 2
- 125000002755 pyrazolinyl group Chemical group 0.000 abstract description 2
- 210000004881 tumor cell Anatomy 0.000 abstract description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 230000010261 cell growth Effects 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000004094 surface-active agent Substances 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
- 239000000243 solution Substances 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 4
- 229930012538 Paclitaxel Natural products 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 229960003668 docetaxel Drugs 0.000 description 4
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- GBHCABUWWQUMAJ-UHFFFAOYSA-N 2-hydrazinoethanol Chemical compound NNCCO GBHCABUWWQUMAJ-UHFFFAOYSA-N 0.000 description 2
- YWLXLRUDGLRYDR-LUPIKGFISA-N 7-epi-10-deacetylbaccatin iii Chemical group O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-LUPIKGFISA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229940123237 Taxane Drugs 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003219 pyrazolines Chemical class 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- LCBRTOBUIDCSID-ZHPRIASZSA-N 19-Hydroxy-10-deacetylbaccatin III Natural products O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(CO)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 LCBRTOBUIDCSID-ZHPRIASZSA-N 0.000 description 1
- KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical class C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- UNPLRYRWJLTVAE-UHFFFAOYSA-N Cloperastine hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)OCCN1CCCCC1 UNPLRYRWJLTVAE-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 241001072332 Monia Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000002634 anti-blastic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- -1 isobutenyl Chemical group 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
Classifications
-
- 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
- C07D491/02—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 two hetero rings
- C07D491/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- C07D491/18—Bridged systems
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.式(1): [式中、 R1及びR2は、水素原子であるか、或いはR1は、水素であり、R2は、ヒドロ キシ、アルコキシ又はアシルオキシ基であるか、或いはR1及びR2は、一緒にな って式: で示される環式のカルボナート又は環式のチオカルボナート基を形成し; R3は、水素又はヒドロキシであり; R4は、水素、又は式(2): (式中、R5は、C1−C5アルキル若しくはC2-C5アルケニル基、又はアリール 基であり;R6は、R5と同一の意味を有するか、又はtert−ブトキシ基である) で示されるイソセリン基である]で示される化合物。 2.R1、R2、R3、及びR4が、水素である、請求項1記載の化合物。 3.R1、R2、R3、及びR4が、式(2)の基(ここで、R5及びR6は、フェニ ルである)である、請求項1記載の化合物。 4.R1、R2、及びR3が、水素であり、R4が、式(2)の基(ここで、R5は 、フェニルであり、R6は、tert−ブトキシである)である、請求項1記載の化 合物。 5.R1、R2、及びR3が、水素であり、R4が、式(2)の基(ここで、R5は 、イソブチルであり、R6は、tert−ブトキシである)である、請求項1記載の 化合物。 6.R1及びR2が、一緒になって環式のカルボナート基を形成し、R3が、水素 であり、R4が、イソセリン基(ここでR5が、フェニルであり、R6が、tert− ブトキシである)である、請求項1記載の化合物。 7.10−デアセチル−10−デヒドロ−バッカチンIII 2−α又はβ−ピラ ゾリン; 10−デアセチル−10−デヒドロ−パクリタキセルピラゾリン; 10−デヒドロ−13−(N−Boc−フェニルイソセリニル)−10−デア セチル−バッカチンIII; 13−(N−Boc−フェニルイソセリニル)−10−デヒドロ−10−デア セチル−バッカチンIIIピラゾリン; 13−(N−Boc−3’−イソブチル)−イソセリニル−10−デヒドロバ ッカチンIIIピラゾリン; 13−(N−Boc−フェニル−イソセリニル)−1,14−カルボナート− 10−デヒドロ−10−デアセチル−バッカチンIIIピラゾリン; から選択される、請求項1記載の化合物。 8.請求項1の化合物の調製方法であって、式(3):[式中、R1、R2、R3、及びR4は、上記のとおりである]で示されるタキサン から出発し、アルコール中でのヒドラジンとの反応による方法。 9.メタノール中で行う、請求項8記載の方法。 10.活性成分として請求項1の化合物を適当な担体と混合して含有する医薬組 成物。 11.細胞毒性及び抗腫瘍薬の製造のための請求項1の化合物の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT96MI000942A IT1283633B1 (it) | 1996-05-10 | 1996-05-10 | Derivati tassanici loro sintesi e formulazioni che li contengono |
IT96A000942 | 1996-05-10 | ||
PCT/EP1997/002198 WO1997043291A1 (en) | 1996-05-10 | 1997-04-29 | Taxane derivatives, the preparation thereof and formulations containing them |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2000513716A true JP2000513716A (ja) | 2000-10-17 |
JP3423002B2 JP3423002B2 (ja) | 2003-07-07 |
Family
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Family Applications (1)
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JP54044497A Expired - Fee Related JP3423002B2 (ja) | 1996-05-10 | 1997-04-29 | タキサン誘導体、その調製、及びそれを含有する処方物 |
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Country | Link |
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US (1) | US5955489A (ja) |
EP (1) | EP0901492B1 (ja) |
JP (1) | JP3423002B2 (ja) |
KR (1) | KR100314382B1 (ja) |
CN (1) | CN1097055C (ja) |
AT (1) | ATE220680T1 (ja) |
AU (1) | AU715748B2 (ja) |
CA (1) | CA2253912C (ja) |
CZ (1) | CZ287489B6 (ja) |
DE (1) | DE69714040T2 (ja) |
DK (1) | DK0901492T3 (ja) |
ES (1) | ES2180985T3 (ja) |
HK (1) | HK1019603A1 (ja) |
HU (1) | HU224965B1 (ja) |
IT (1) | IT1283633B1 (ja) |
NO (1) | NO322266B1 (ja) |
PL (1) | PL185778B1 (ja) |
PT (1) | PT901492E (ja) |
RU (1) | RU2168513C2 (ja) |
SK (1) | SK282471B6 (ja) |
WO (1) | WO1997043291A1 (ja) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003026673A (ja) * | 1999-03-05 | 2003-01-29 | Asahi Kasei Corp | 骨形成促進剤 |
WO2001024763A2 (en) | 1999-10-01 | 2001-04-12 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
ITMI20012185A1 (it) * | 2001-10-19 | 2003-04-19 | Indena Spa | Procedimento per la preparazione della 14beta-idrossi-baccatina iii-1,14-carbonato |
ITMI20012186A1 (it) | 2001-10-19 | 2003-04-19 | Indena Spa | Procedimento per la preparazione della 14-beta-idrossi-baccatina iii-1,14-carbonato |
WO2006122408A1 (en) | 2005-05-18 | 2006-11-23 | Aegera Therapeutics Inc. | Bir domain binding compounds |
NZ572836A (en) | 2006-05-16 | 2011-12-22 | Pharmascience Inc | Iap bir domain binding compounds |
EP2080764B1 (en) | 2008-01-18 | 2012-08-22 | INDENA S.p.A. | Solid forms of ortataxel |
EP2534170B1 (en) | 2010-02-12 | 2017-04-19 | Pharmascience Inc. | Iap bir domain binding compounds |
CN113603660B (zh) * | 2021-09-02 | 2024-01-05 | 无锡紫杉药业有限公司 | 一种10-羰基多西他赛的制备方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2601785B1 (fr) * | 1986-07-15 | 1989-07-28 | Telecommunications Sa | Dispositif de reserve pour cable a fibre optique et le procede de mise en oeuvre |
FR2601675B1 (fr) * | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Derives du taxol, leur preparation et les compositions pharmaceutiques qui les contiennent |
US5393886A (en) * | 1993-05-05 | 1995-02-28 | The Du Pont Merck Pharmaceutical Company | Intermediates for the synthesis of anthrapyrazolone anticancer agents |
IT1275936B1 (it) * | 1995-03-17 | 1997-10-24 | Indena Spa | Derivati della 10-deacetilbaccatina iii e della 10-deacetil-14b- idrossibaccatina iii loro metodo di preparazione e formulazioni |
IT1275435B (it) * | 1995-05-19 | 1997-08-07 | Indena Spa | Derivati della 10-desacetil-14beta-idrossibaccatina iii,loro metodo di preparazione e formulazioni che li contengono |
-
1996
- 1996-05-10 IT IT96MI000942A patent/IT1283633B1/it active IP Right Grant
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1997
- 1997-04-29 SK SK1539-98A patent/SK282471B6/sk not_active IP Right Cessation
- 1997-04-29 DK DK97922918T patent/DK0901492T3/da active
- 1997-04-29 DE DE69714040T patent/DE69714040T2/de not_active Expired - Lifetime
- 1997-04-29 CZ CZ19983619A patent/CZ287489B6/cs not_active IP Right Cessation
- 1997-04-29 WO PCT/EP1997/002198 patent/WO1997043291A1/en active IP Right Grant
- 1997-04-29 AT AT97922918T patent/ATE220680T1/de active
- 1997-04-29 US US09/155,959 patent/US5955489A/en not_active Expired - Lifetime
- 1997-04-29 EP EP97922918A patent/EP0901492B1/en not_active Expired - Lifetime
- 1997-04-29 CA CA002253912A patent/CA2253912C/en not_active Expired - Fee Related
- 1997-04-29 KR KR1019980709041A patent/KR100314382B1/ko not_active IP Right Cessation
- 1997-04-29 PL PL97329768A patent/PL185778B1/pl not_active IP Right Cessation
- 1997-04-29 CN CN97194491A patent/CN1097055C/zh not_active Expired - Fee Related
- 1997-04-29 RU RU98122311/04A patent/RU2168513C2/ru not_active IP Right Cessation
- 1997-04-29 ES ES97922918T patent/ES2180985T3/es not_active Expired - Lifetime
- 1997-04-29 PT PT97922918T patent/PT901492E/pt unknown
- 1997-04-29 HU HU9903649A patent/HU224965B1/hu not_active IP Right Cessation
- 1997-04-29 JP JP54044497A patent/JP3423002B2/ja not_active Expired - Fee Related
- 1997-04-29 AU AU28886/97A patent/AU715748B2/en not_active Ceased
-
1998
- 1998-11-06 NO NO19985187A patent/NO322266B1/no not_active IP Right Cessation
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1999
- 1999-10-27 HK HK99104797A patent/HK1019603A1/xx not_active IP Right Cessation
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