AU722684B2 - 6-thio-substituted paclitaxels - Google Patents
6-thio-substituted paclitaxels Download PDFInfo
- Publication number
- AU722684B2 AU722684B2 AU57922/98A AU5792298A AU722684B2 AU 722684 B2 AU722684 B2 AU 722684B2 AU 57922/98 A AU57922/98 A AU 57922/98A AU 5792298 A AU5792298 A AU 5792298A AU 722684 B2 AU722684 B2 AU 722684B2
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- Australia
- Prior art keywords
- alkyl
- sch
- hydrogen
- och
- compound
- 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.)
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- 125000002456 taxol group Chemical class 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 105
- 150000001875 compounds Chemical class 0.000 claims description 82
- -1 dimethylaminoethyl Chemical group 0.000 claims description 60
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 20
- 230000000259 anti-tumor effect Effects 0.000 claims description 15
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000000468 ketone group Chemical group 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 230000004614 tumor growth Effects 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 125000002541 furyl group Chemical group 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
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 2
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract description 4
- 150000004579 taxol derivatives Chemical class 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 296
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 148
- 235000019439 ethyl acetate Nutrition 0.000 description 109
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 88
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 81
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 77
- 239000000243 solution Substances 0.000 description 70
- 239000000741 silica gel Substances 0.000 description 48
- 229910002027 silica gel Inorganic materials 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 47
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
- 238000005481 NMR spectroscopy Methods 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 42
- 239000007787 solid Substances 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 36
- 239000012267 brine Substances 0.000 description 35
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
- 239000000203 mixture Substances 0.000 description 29
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 229960001592 paclitaxel Drugs 0.000 description 25
- 101150041968 CDC13 gene Proteins 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- 230000000704 physical effect Effects 0.000 description 19
- 239000000377 silicon dioxide Substances 0.000 description 19
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
- 229940123237 Taxane Drugs 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 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 17
- 238000004587 chromatography analysis Methods 0.000 description 16
- 238000000132 electrospray ionisation Methods 0.000 description 16
- 239000000843 powder Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 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 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 229930012538 Paclitaxel Natural products 0.000 description 14
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 14
- 206010028980 Neoplasm Diseases 0.000 description 12
- WILBTFWIBAOWLN-UHFFFAOYSA-N triethyl(triethylsilyloxy)silane Chemical compound CC[Si](CC)(CC)O[Si](CC)(CC)CC WILBTFWIBAOWLN-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 150000003573 thiols Chemical class 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 150000003462 sulfoxides Chemical class 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
- 150000001336 alkenes Chemical class 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
- 150000002009 diols Chemical class 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- TZGODTCAKVHMFG-UHFFFAOYSA-N sulfanylmethoxymethanethiol Chemical compound SCOCS TZGODTCAKVHMFG-UHFFFAOYSA-N 0.000 description 6
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
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- 239000000706 filtrate Substances 0.000 description 5
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical compound CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
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- 125000001424 substituent group Chemical group 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- UIYCHXAGWOYNNA-UHFFFAOYSA-N vinyl sulfide Chemical compound C=CSC=C UIYCHXAGWOYNNA-UHFFFAOYSA-N 0.000 description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 3
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- 206010009944 Colon cancer Diseases 0.000 description 3
- 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 3
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- 125000003342 alkenyl group Chemical group 0.000 description 3
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- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
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- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 3
- 238000012746 preparative thin layer chromatography Methods 0.000 description 3
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- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 2
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 2
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- YUCBLVFHJWOYDN-PPIALRKJSA-N 4-[(r)-[(2r,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]-1-[(r)-[(2r,4r,5s)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]phthalazine Chemical compound C1=C(OC)C=C2C([C@@H](OC=3C4=CC=CC=C4C(O[C@@H]([C@@H]4N5CC[C@@H]([C@@H](C5)CC)C4)C=4C5=CC(OC)=CC=C5N=CC=4)=NN=3)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 YUCBLVFHJWOYDN-PPIALRKJSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- 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
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/6551—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a four-membered ring
- C07F9/65512—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a four-membered ring condensed with carbocyclic rings or carbocyclic ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3341996P | 1996-12-24 | 1996-12-24 | |
| US60/033419 | 1996-12-24 | ||
| US3635197P | 1997-01-23 | 1997-01-23 | |
| US60/036351 | 1997-01-23 | ||
| PCT/US1997/022152 WO1998028288A1 (en) | 1996-12-24 | 1997-12-05 | 6-thio-substituted paclitaxels |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU5792298A AU5792298A (en) | 1998-07-17 |
| AU722684B2 true AU722684B2 (en) | 2000-08-10 |
Family
ID=26709670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU57922/98A Ceased AU722684B2 (en) | 1996-12-24 | 1997-12-05 | 6-thio-substituted paclitaxels |
Country Status (11)
| Country | Link |
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| EP (1) | EP0960107B1 (cg-RX-API-DMAC7.html) |
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| AT (1) | ATE225341T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU722684B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2268774A1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE69716135T2 (cg-RX-API-DMAC7.html) |
| DK (1) | DK0960107T3 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2184149T3 (cg-RX-API-DMAC7.html) |
| PT (1) | PT960107E (cg-RX-API-DMAC7.html) |
| WO (1) | WO1998028288A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HK1049787B (en) | 1999-10-01 | 2014-07-25 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| US6362217B2 (en) | 2000-03-17 | 2002-03-26 | Bristol-Myers Squibb Company | Taxane anticancer agents |
| US6656966B2 (en) | 2000-06-22 | 2003-12-02 | Nitromed, Inc. | Nitrosated and nitrosylated taxanes, compositions and methods of use |
| US7351542B2 (en) | 2002-05-20 | 2008-04-01 | The Regents Of The University Of California | Methods of modulating tubulin deacetylase activity |
| DK1530465T4 (en) | 2002-06-26 | 2016-03-21 | Medigene Ag | A method of producing a cationic liposomal preparation comprising a lipophilic compound. |
| CA2525647A1 (en) | 2003-05-16 | 2005-02-24 | Intermune, Inc. | Synthetic chemokine receptor ligands and methods of use thereof |
| US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
| WO2006089218A2 (en) | 2005-02-17 | 2006-08-24 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for modulating angiogenesis |
| US8168216B2 (en) | 2006-03-22 | 2012-05-01 | Medigene Ag | Treatment of triple receptor negative breast cancer |
| PL217731B1 (pl) | 2006-06-01 | 2014-08-29 | Tomasz Byrski | Sposób wykrywania genetycznie uwarunkowanej obniżonej odpowiedzi na chemioterapię cytostatykiem taksanowym, zastosowanie mutacji założycielskiej oraz zestawu do wykrywania takiej odpowiedzi |
| CA2724550C (en) | 2008-05-22 | 2017-01-03 | Kereos, Inc. | Combination antitumor therapy |
| WO2010005850A1 (en) | 2008-07-08 | 2010-01-14 | The J. David Gladstone Institutes | Methods and compositions for modulating angiogenesis |
| CN102040570B (zh) * | 2009-10-14 | 2014-07-30 | 江苏先声药物研究有限公司 | 硫代紫杉烷类衍生物及其制备方法和用途 |
| RU2015105588A (ru) | 2012-07-19 | 2016-09-10 | Редвуд Байосайнс, Инк. | Антитело, специфическое к cd22, и способы его применения |
| JP2016500058A (ja) | 2012-11-12 | 2016-01-07 | レッドウッド バイオサイエンス， インコーポレイテッド | 化合物および抱合体を生成するための方法 |
| PL3300745T3 (pl) | 2013-02-15 | 2020-03-31 | The Regents Of The University Of California | Chimeryczny receptor antygenowy i sposoby jego zastosowania |
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| US9493413B2 (en) | 2013-11-27 | 2016-11-15 | Redwood Bioscience, Inc. | Hydrazinyl-pyrrolo compounds and methods for producing a conjugate |
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| CN110841074B (zh) | 2014-03-21 | 2023-07-18 | 艾伯维公司 | 抗-egfr抗体及抗体药物偶联物 |
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| EP3231421A1 (en) | 2016-04-11 | 2017-10-18 | Greenaltech, S.L. | Uses of a carotenoid in the treatment or prevention of stress induced conditions |
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| CA3203652A1 (en) | 2020-11-13 | 2022-05-19 | William Robert ARATHOON | Anti-mrp4 (encoded by abcc4 gene) antibodies and uses thereof |
| CA3201005A1 (en) | 2020-11-20 | 2022-05-27 | R.P. Scherer Technologies, Llc | Glycoside dual-cleavage linkers for antibody-drug conjugates |
| AR124681A1 (es) | 2021-01-20 | 2023-04-26 | Abbvie Inc | Conjugados anticuerpo-fármaco anti-egfr |
| US20250051471A1 (en) | 2021-12-13 | 2025-02-13 | William Robert Arathoon Living Trust Dated August 29, 2016 | Anti-Abcb1 Antibodies |
| WO2023159220A1 (en) | 2022-02-18 | 2023-08-24 | Kenjockety Biotechnology, Inc. | Anti-cd47 antibodies |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2601675B1 (fr) * | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Derives du taxol, leur preparation et les compositions pharmaceutiques qui les contiennent |
| US4876399A (en) * | 1987-11-02 | 1989-10-24 | Research Corporation Technologies, Inc. | Taxols, their preparation and intermediates thereof |
| US4960790A (en) * | 1989-03-09 | 1990-10-02 | University Of Kansas | Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof |
| US5714512A (en) * | 1991-07-08 | 1998-02-03 | Rhone-Poulenc Rorer, S.A. | Compositions containing taxane derivatives |
| CZ287609B6 (cs) * | 1991-09-23 | 2001-01-17 | Florida State University | Deriváty 10-deacetoxytaxolu |
| US5272171A (en) * | 1992-02-13 | 1993-12-21 | Bristol-Myers Squibb Company | Phosphonooxy and carbonate derivatives of taxol |
| ES2134847T3 (es) * | 1992-04-17 | 1999-10-16 | Abbott Lab | Derivados de taxol. |
| US5254580A (en) * | 1993-01-19 | 1993-10-19 | Bristol-Myers Squibb Company | 7,8-cyclopropataxanes |
| US5294637A (en) * | 1992-07-01 | 1994-03-15 | Bristol-Myers Squibb Company | Fluoro taxols |
| FR2697019B1 (fr) * | 1992-10-15 | 1994-11-25 | Rhone Poulenc Rorer Sa | Nouveaux dérivés du taxane, leur préparation et les compositions pharmaceutiques qui les contiennent. |
| CA2109861C (en) * | 1992-12-04 | 1999-03-16 | Shu-Hui Chen | 6,7-modified paclitaxels |
| KR100356448B1 (ko) * | 1992-12-23 | 2002-10-19 | 브리스톨-마이어스스퀴브컴파니 | 신규 측쇄-함유 탁산 및 그의 중간체 화합물 |
| MX9308012A (es) * | 1992-12-24 | 1994-08-31 | Bristol Myers Squibb Co | Eteres fosfonooximetilicos de derivados de taxano, solubles en agua y composiciones farmaceuticas que los incluyen. |
| US6066747A (en) * | 1993-03-05 | 2000-05-23 | Florida State University | Process for the preparation of 9-desoxotaxanes |
| US5703247A (en) * | 1993-03-11 | 1997-12-30 | Virginia Tech Intellectual Properties, Inc. | 2-Debenzoyl-2-acyl taxol derivatives and methods for making same |
| NZ330671A (en) * | 1993-06-11 | 2000-01-28 | Upjohn Co | 13-Substituted-(Oxazolidin-4-yl)-oxycarbonyl-delta-6,7-taxols |
| US5767296A (en) * | 1994-06-09 | 1998-06-16 | Daiichi Pharmaceutical Co., Ltd. | Deacetoxytaxol derivatives |
| NZ288802A (en) * | 1994-06-28 | 1998-05-27 | Upjohn Co | Ether taxol derivatives, preparation and pharmaceutical compositions thereof |
| CA2195844C (en) * | 1994-07-26 | 2001-10-09 | Ezio Bombardelli | Semi-synthetic taxanes with anti-tumoural activity |
-
1997
- 1997-11-26 US US08/979,139 patent/US5977386A/en not_active Expired - Fee Related
- 1997-12-05 ES ES97954044T patent/ES2184149T3/es not_active Expired - Lifetime
- 1997-12-05 CA CA002268774A patent/CA2268774A1/en not_active Abandoned
- 1997-12-05 WO PCT/US1997/022152 patent/WO1998028288A1/en not_active Ceased
- 1997-12-05 PT PT97954044T patent/PT960107E/pt unknown
- 1997-12-05 AT AT97954044T patent/ATE225341T1/de not_active IP Right Cessation
- 1997-12-05 JP JP52877098A patent/JP2001507029A/ja not_active Abandoned
- 1997-12-05 AU AU57922/98A patent/AU722684B2/en not_active Ceased
- 1997-12-05 EP EP97954044A patent/EP0960107B1/en not_active Expired - Lifetime
- 1997-12-05 DE DE69716135T patent/DE69716135T2/de not_active Expired - Fee Related
- 1997-12-05 DK DK97954044T patent/DK0960107T3/da active
Also Published As
| Publication number | Publication date |
|---|---|
| ATE225341T1 (de) | 2002-10-15 |
| EP0960107B1 (en) | 2002-10-02 |
| DE69716135T2 (de) | 2003-06-05 |
| DE69716135D1 (en) | 2002-11-07 |
| JP2001507029A (ja) | 2001-05-29 |
| DK0960107T3 (da) | 2003-02-10 |
| ES2184149T3 (es) | 2003-04-01 |
| EP0960107A1 (en) | 1999-12-01 |
| US5977386A (en) | 1999-11-02 |
| EP0960107A4 (cg-RX-API-DMAC7.html) | 1999-12-01 |
| CA2268774A1 (en) | 1998-07-02 |
| WO1998028288A1 (en) | 1998-07-02 |
| AU5792298A (en) | 1998-07-17 |
| PT960107E (pt) | 2003-02-28 |
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Legal Events
| Date | Code | Title | Description |
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| FGA | Letters patent sealed or granted (standard patent) |