IL107950A - b 7, b 8 - Matano - Taxols, their preparation and pharmaceutical preparations against malignant tumors containing them - Google Patents
b 7, b 8 - Matano - Taxols, their preparation and pharmaceutical preparations against malignant tumors containing themInfo
- Publication number
- IL107950A IL107950A IL10795093A IL10795093A IL107950A IL 107950 A IL107950 A IL 107950A IL 10795093 A IL10795093 A IL 10795093A IL 10795093 A IL10795093 A IL 10795093A IL 107950 A IL107950 A IL 107950A
- Authority
- IL
- Israel
- Prior art keywords
- nhc
- deoxy
- methanotaxol
- phenyl
- taxol
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title description 200
- 230000000118 anti-neoplastic effect Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 153
- 229960001592 paclitaxel Drugs 0.000 claims abstract description 151
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 120
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 70
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 52
- -1 nitro, 2-furyl Chemical group 0.000 claims description 51
- 125000005843 halogen group Chemical group 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 125000004414 alkyl thio group Chemical group 0.000 claims description 25
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 25
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 229940063683 taxotere Drugs 0.000 claims description 12
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 11
- 125000000524 functional group Chemical group 0.000 claims description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 230000002378 acidificating effect Effects 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 150000004820 halides Chemical class 0.000 claims description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 4
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 4
- 125000005544 phthalimido group Chemical group 0.000 claims description 4
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- 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 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 3
- 230000000259 anti-tumor effect Effects 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 7
- 239000013256 coordination polymer Substances 0.000 claims 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 2
- 101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 claims 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000006000 trichloroethyl group Chemical group 0.000 claims 1
- 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 abstract description 63
- 229930012538 Paclitaxel Natural products 0.000 abstract description 51
- 206010028980 Neoplasm Diseases 0.000 abstract description 8
- 208000032839 leukemia Diseases 0.000 abstract description 7
- 206010006187 Breast cancer Diseases 0.000 abstract description 4
- 206010033128 Ovarian cancer Diseases 0.000 abstract description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 abstract description 4
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 abstract description 4
- 206010017758 gastric cancer Diseases 0.000 abstract description 4
- 201000010536 head and neck cancer Diseases 0.000 abstract description 4
- 201000005202 lung cancer Diseases 0.000 abstract description 4
- 201000001441 melanoma Diseases 0.000 abstract description 4
- KNDOYLWKJXBKBV-ABSZOUAASA-N 7-deoxypaclitaxel Chemical class O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)CC[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 KNDOYLWKJXBKBV-ABSZOUAASA-N 0.000 abstract description 3
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 3
- 206010009944 Colon cancer Diseases 0.000 abstract description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 abstract description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 abstract description 3
- 208000029742 colonic neoplasm Diseases 0.000 abstract description 3
- 208000014829 head and neck neoplasm Diseases 0.000 abstract description 3
- 208000020816 lung neoplasm Diseases 0.000 abstract description 3
- 201000011549 stomach cancer Diseases 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 223
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 176
- 238000006243 chemical reaction Methods 0.000 description 138
- 239000000243 solution Substances 0.000 description 115
- 235000019439 ethyl acetate Nutrition 0.000 description 93
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 88
- 239000000741 silica gel Substances 0.000 description 82
- 229910002027 silica gel Inorganic materials 0.000 description 82
- 238000005481 NMR spectroscopy Methods 0.000 description 79
- 101150041968 CDC13 gene Proteins 0.000 description 73
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 73
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- 239000000047 product Substances 0.000 description 72
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 70
- 238000000034 method Methods 0.000 description 69
- 239000000203 mixture Substances 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 60
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 52
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- 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 description 44
- 239000010410 layer Substances 0.000 description 44
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 39
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 38
- 229940093499 ethyl acetate Drugs 0.000 description 38
- 239000012043 crude product Substances 0.000 description 34
- 239000012044 organic layer Substances 0.000 description 33
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
- 239000002253 acid Substances 0.000 description 30
- 238000004949 mass spectrometry Methods 0.000 description 27
- 125000001424 substituent group Chemical group 0.000 description 27
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 26
- 150000001412 amines Chemical group 0.000 description 25
- 229930014667 baccatin III Natural products 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 229940073584 methylene chloride Drugs 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 20
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 19
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 125000003118 aryl group Chemical group 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- 150000003751 zinc Chemical class 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 229910052740 iodine Inorganic materials 0.000 description 15
- 150000001721 carbon Chemical group 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 13
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 229960004756 ethanol Drugs 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 239000007795 chemical reaction product Substances 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 229910052751 metal Inorganic materials 0.000 description 11
- 239000002184 metal Substances 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 238000001819 mass spectrum Methods 0.000 description 9
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000010626 work up procedure Methods 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 8
- 238000010828 elution Methods 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 231100000252 nontoxic Toxicity 0.000 description 8
- 230000003000 nontoxic effect Effects 0.000 description 8
- GYKKMBWZXQCCPB-GOHIFREVSA-M potassium;(4s,5r)-2-(2,4-dimethoxyphenyl)-3-[(2-methylpropan-2-yl)oxycarbonyl]-4-phenyl-1,3-oxazolidine-5-carboxylate Chemical compound [K+].COC1=CC(OC)=CC=C1C1N(C(=O)OC(C)(C)C)[C@@H](C=2C=CC=CC=2)[C@H](C([O-])=O)O1 GYKKMBWZXQCCPB-GOHIFREVSA-M 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
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- 238000004440 column chromatography Methods 0.000 description 7
- 150000002917 oxazolidines Chemical class 0.000 description 7
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 6
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- SAVQQRYWWAGSQW-UHFFFAOYSA-N n-methyl-n-(trifluoro-$l^{4}-sulfanyl)methanamine Chemical compound CN(C)S(F)(F)F SAVQQRYWWAGSQW-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
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- 230000003595 spectral effect Effects 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- BTTYYCFULLUOIV-UHFFFAOYSA-N 1-(dimethoxymethyl)-2,4-dimethoxybenzene Chemical compound COC(OC)C1=CC=C(OC)C=C1OC BTTYYCFULLUOIV-UHFFFAOYSA-N 0.000 description 5
- TYLVGQKNNUHXIP-MHHARFCSSA-N 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)C=4C=CC=CC=4)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 TYLVGQKNNUHXIP-MHHARFCSSA-N 0.000 description 5
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 5
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- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
- 239000012346 acetyl chloride Substances 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 5
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- 150000002576 ketones Chemical class 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000029565 malignant colon neoplasm Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- VLKYMHSOQDMQNF-DTWKUNHWSA-N methyl (2r,3s)-3-azido-2-hydroxy-3-phenylpropanoate Chemical compound COC(=O)[C@H](O)[C@@H](N=[N+]=[N-])C1=CC=CC=C1 VLKYMHSOQDMQNF-DTWKUNHWSA-N 0.000 description 1
- KUHYOPYTKRSGIQ-YGHPRADISA-N methyl (4s,5r)-3-benzoyl-2-(2,4-dimethoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate Chemical compound C1([C@@H]2N(C(O[C@H]2C(=O)OC)C=2C(=CC(OC)=CC=2)OC)C(=O)C=2C=CC=CC=2)=CC=CC=C1 KUHYOPYTKRSGIQ-YGHPRADISA-N 0.000 description 1
- QKGSHZOMWJRBRK-ZXABPTRBSA-N methyl (4s,5r)-3-benzyl-2-(2,4-dimethoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate Chemical compound O([C@H]([C@@H]1C=2C=CC=CC=2)C(=O)OC)C(C=2C(=CC(OC)=CC=2)OC)N1CC1=CC=CC=C1 QKGSHZOMWJRBRK-ZXABPTRBSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical compound C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 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
- LIUZBZJUDLPOPX-UHFFFAOYSA-N n-[diethylamino(difluoro)-$l^{4}-sulfanyl]-n-ethylethanamine Chemical compound CCN(CC)S(F)(F)N(CC)CC LIUZBZJUDLPOPX-UHFFFAOYSA-N 0.000 description 1
- JLXBTRGANPQOKN-UHFFFAOYSA-N n-[dimethylamino(difluoro)-$l^{4}-sulfanyl]-n-ethylethanamine Chemical compound CCN(CC)S(F)(F)N(C)C JLXBTRGANPQOKN-UHFFFAOYSA-N 0.000 description 1
- WKQAVDBVXQOLBB-UHFFFAOYSA-N n-[dimethylamino(difluoro)-$l^{4}-sulfanyl]-n-methylmethanamine Chemical compound CN(C)S(F)(F)N(C)C WKQAVDBVXQOLBB-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- KGTDRFCXGRULNK-JYOBTZKQSA-N nogalamycin Chemical compound CO[C@@H]1[C@@](OC)(C)[C@@H](OC)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=C4[C@@]5(C)O[C@H]([C@H]([C@@H]([C@H]5O)N(C)C)O)OC4=C3C3=O)=C3C=C2[C@@H](C(=O)OC)[C@@](C)(O)C1 KGTDRFCXGRULNK-JYOBTZKQSA-N 0.000 description 1
- 229950009266 nogalamycin Drugs 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- OVKJCXDXNYSAAF-MUSUQGPOSA-M potassium;(4s,5r)-3-benzoyl-2-(2,4-dimethoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate Chemical compound [K+].COC1=CC(OC)=CC=C1C1N(C(=O)C=2C=CC=CC=2)[C@@H](C=2C=CC=CC=2)[C@H](C([O-])=O)O1 OVKJCXDXNYSAAF-MUSUQGPOSA-M 0.000 description 1
- MQKGQIZUCZDRIM-XUKNZQTLSA-M potassium;(4s,5r)-3-benzyl-2-(2,4-dimethoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate Chemical compound [K+].COC1=CC(OC)=CC=C1C1N(CC=2C=CC=CC=2)[C@@H](C=2C=CC=CC=2)[C@H](C([O-])=O)O1 MQKGQIZUCZDRIM-XUKNZQTLSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 description 1
- KZJPVUDYAMEDRM-UHFFFAOYSA-M silver;2,2,2-trifluoroacetate Chemical compound [Ag+].[O-]C(=O)C(F)(F)F KZJPVUDYAMEDRM-UHFFFAOYSA-M 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000012257 stirred material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 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 description 1
- 125000002456 taxol group Chemical group 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000012991 xanthate Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D263/06—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US99057992A | 1992-12-15 | 1992-12-15 | |
US1382693A | 1993-02-02 | 1993-02-02 | |
US7633793A | 1993-06-11 | 1993-06-11 | |
US12297493A | 1993-09-17 | 1993-09-17 |
Publications (2)
Publication Number | Publication Date |
---|---|
IL107950A0 IL107950A0 (en) | 1994-04-12 |
IL107950A true IL107950A (en) | 2001-04-30 |
Family
ID=27486333
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL10795093A IL107950A (en) | 1992-12-15 | 1993-12-09 | b 7, b 8 - Matano - Taxols, their preparation and pharmaceutical preparations against malignant tumors containing them |
Country Status (26)
Country | Link |
---|---|
US (1) | US6911549B1 (pl) |
EP (1) | EP0674630B1 (pl) |
JP (1) | JP3441458B2 (pl) |
KR (1) | KR100317015B1 (pl) |
CN (2) | CN1062561C (pl) |
AT (1) | ATE226576T1 (pl) |
AU (1) | AU687027B2 (pl) |
CA (1) | CA2149021A1 (pl) |
CZ (1) | CZ291177B6 (pl) |
DE (1) | DE69332438T2 (pl) |
DK (1) | DK0674630T3 (pl) |
ES (1) | ES2187519T3 (pl) |
FI (1) | FI111633B (pl) |
HU (1) | HUT74447A (pl) |
IL (1) | IL107950A (pl) |
LV (1) | LV13023B (pl) |
MX (1) | MX9307777A (pl) |
MY (1) | MY116473A (pl) |
NO (1) | NO313801B1 (pl) |
NZ (1) | NZ259196A (pl) |
PL (1) | PL185042B1 (pl) |
PT (1) | PT674630E (pl) |
RU (1) | RU2125996C1 (pl) |
SK (1) | SK281897B6 (pl) |
TW (1) | TW389758B (pl) |
WO (1) | WO1994013655A1 (pl) |
Families Citing this family (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5710287A (en) | 1991-09-23 | 1998-01-20 | Florida State University | Taxanes having an amino substituted side-chain and pharmaceutical compositions containing them |
US5998656A (en) * | 1991-09-23 | 1999-12-07 | Florida State University | C10 tricyclic taxanes |
FR2697752B1 (fr) | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Compositions antitumorales contenant des dérivés du taxane. |
FR2698871B1 (fr) * | 1992-12-09 | 1995-02-24 | Rhone Poulenc Rorer Sa | Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
US5814658A (en) * | 1992-12-09 | 1998-09-29 | Rhone-Poulenc Rorer S.A. | Taxoids, their preparation and pharmaceutical compositions containing them |
US5973160A (en) | 1992-12-23 | 1999-10-26 | Poss; Michael A. | Methods for the preparation of novel sidechain-bearing taxanes |
FR2712288B1 (fr) * | 1993-11-08 | 1996-01-05 | Rhone Poulenc Rorer Sa | Nouveaux taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
GB9409131D0 (en) * | 1994-05-09 | 1994-06-29 | Erba Carlo Spa | Unsaturated taxane compounds |
FR2726272B1 (fr) * | 1994-10-26 | 1996-12-06 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
WO1996014309A1 (en) * | 1994-11-04 | 1996-05-17 | Pharmacia & Upjohn S.P.A | Taxane derivatives |
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 |
FR2732342B1 (fr) * | 1995-04-03 | 1997-04-30 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
FR2742751B1 (fr) * | 1995-12-22 | 1998-01-30 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
US5635531A (en) * | 1996-07-08 | 1997-06-03 | Bristol-Myers Squibb Company | 3'-aminocarbonyloxy paclitaxels |
US5773464A (en) * | 1996-09-30 | 1998-06-30 | Bristol-Myers Squibb Company | C-10 epoxy taxanes |
WO1998017656A1 (en) * | 1996-10-24 | 1998-04-30 | Institute Armand-Frappier | A family of canadensol taxanes, the semi-synthetic preparation and therapeutic use thereof |
US6017935A (en) * | 1997-04-24 | 2000-01-25 | Bristol-Myers Squibb Company | 7-sulfur substituted paclitaxels |
US6156789A (en) * | 1998-03-17 | 2000-12-05 | Rhone-Poulenc Rorer S.A. | Method for treating abnormal cell proliferation in the brain |
AU3481001A (en) * | 2000-02-02 | 2001-08-14 | Florida State University Research Foundation, Inc. | Taxane formulations having improved solubility |
RU2264400C2 (ru) | 2000-02-02 | 2005-11-20 | Флорида Стейт Юниверсити Рисерч Фаундейшн, Инк. | Таксан, фармацевтическая композиция на его основе и способ ингибирования роста опухоли |
US6649632B2 (en) | 2000-02-02 | 2003-11-18 | Fsu Research Foundation, Inc. | C10 ester substituted taxanes |
CN1362958A (zh) | 2000-02-02 | 2002-08-07 | 佛罗里达州立大学研究基金有限公司 | 用作抗肿瘤剂的c7碳酸酯取代的紫杉烷 |
HUP0302599A3 (en) | 2000-09-22 | 2005-05-30 | Bristol Myers Squibb Co | Method for reducing toxicity of combined chemotherapic compositions |
CA2354478A1 (en) * | 2001-07-31 | 2003-01-31 | Florida State University Research Foundation, Inc. | C10 carbonate substituted taxanes |
SG125888A1 (en) * | 2001-08-01 | 2006-10-30 | Univ Florida State Res Found | C10 carbonate substituted taxanes |
US20040132991A1 (en) * | 2002-10-09 | 2004-07-08 | Phytogen Life Sciences Inc. | Novel taxanes and methods related to use and preparation thereof |
US8703982B2 (en) | 2003-03-17 | 2014-04-22 | Phyton Holdings Llc | Purification of taxanes |
PE20050693A1 (es) | 2004-02-13 | 2005-09-27 | Univ Florida State Res Found | Taxanos sustituidos con esteres de ciclopentilo en c10 |
AU2012202903B2 (en) * | 2005-02-18 | 2014-12-11 | Abraxis Bioscience, Inc. | Drugs with improved hydrophobicity for incorporation in medical devices |
CN105879114A (zh) * | 2005-02-18 | 2016-08-24 | 阿布拉西斯生物科学公司 | 用于整合入医疗装置的疏水性改善的药物 |
BRPI0613005A8 (pt) | 2005-07-15 | 2017-12-26 | Angiochem Inc | uso de polipeptídeos de aprotinina como veículos em conjugados farmacêuticos. |
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1993
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- 1993-12-09 MX MX9307777A patent/MX9307777A/es not_active IP Right Cessation
- 1993-12-13 DK DK94903483T patent/DK0674630T3/da active
- 1993-12-13 CA CA002149021A patent/CA2149021A1/en not_active Abandoned
- 1993-12-13 EP EP94903483A patent/EP0674630B1/en not_active Expired - Lifetime
- 1993-12-13 WO PCT/US1993/011827 patent/WO1994013655A1/en active IP Right Grant
- 1993-12-13 PL PL93309392A patent/PL185042B1/pl not_active IP Right Cessation
- 1993-12-13 NZ NZ259196A patent/NZ259196A/en unknown
- 1993-12-13 AT AT94903483T patent/ATE226576T1/de not_active IP Right Cessation
- 1993-12-13 SK SK788-95A patent/SK281897B6/sk unknown
- 1993-12-13 US US08/454,210 patent/US6911549B1/en not_active Expired - Fee Related
- 1993-12-13 ES ES94903483T patent/ES2187519T3/es not_active Expired - Lifetime
- 1993-12-13 DE DE69332438T patent/DE69332438T2/de not_active Expired - Fee Related
- 1993-12-13 JP JP51431294A patent/JP3441458B2/ja not_active Expired - Fee Related
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- 1993-12-13 CZ CZ19951437A patent/CZ291177B6/cs not_active IP Right Cessation
- 1993-12-13 KR KR1019950702435A patent/KR100317015B1/ko not_active IP Right Cessation
- 1993-12-13 AU AU57411/94A patent/AU687027B2/en not_active Ceased
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1995
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1999
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