CA2268774A1 - 6-thio-substituted paclitaxels - Google Patents
6-thio-substituted paclitaxels Download PDFInfo
- Publication number
- CA2268774A1 CA2268774A1 CA002268774A CA2268774A CA2268774A1 CA 2268774 A1 CA2268774 A1 CA 2268774A1 CA 002268774 A CA002268774 A CA 002268774A CA 2268774 A CA2268774 A CA 2268774A CA 2268774 A1 CA2268774 A1 CA 2268774A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- hydrogen
- compound
- nmr
- sch2s
- 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.)
- Abandoned
Links
- 125000002456 taxol group Chemical class 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 79
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
- -1 dimethylaminoethyl Chemical group 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 230000000259 anti-tumor effect Effects 0.000 claims description 15
- 125000000391 vinyl group Chemical class [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 10
- 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
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000000468 ketone group Chemical group 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 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
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 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
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 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
- 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
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 230000004614 tumor growth Effects 0.000 claims description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) 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
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 150000004820 halides 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
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)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
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract description 4
- 150000004579 taxol derivatives Chemical class 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 301
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 169
- 235000019439 ethyl acetate Nutrition 0.000 description 106
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 93
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 87
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
- 239000000243 solution Substances 0.000 description 70
- 238000005160 1H NMR spectroscopy Methods 0.000 description 52
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 47
- 239000000741 silica gel Substances 0.000 description 47
- 229910002027 silica gel Inorganic materials 0.000 description 47
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 41
- 239000007787 solid Substances 0.000 description 40
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 101150041968 CDC13 gene Proteins 0.000 description 35
- 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 28
- 229960001592 paclitaxel Drugs 0.000 description 27
- 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 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- 229930012538 Paclitaxel Natural products 0.000 description 22
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 20
- 230000000704 physical effect Effects 0.000 description 19
- 239000000377 silicon dioxide Substances 0.000 description 19
- 229940123237 Taxane Drugs 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 238000004587 chromatography analysis Methods 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 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
- 238000000132 electrospray ionisation Methods 0.000 description 16
- 239000000843 powder Substances 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 15
- 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 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- WILBTFWIBAOWLN-UHFFFAOYSA-N triethyl(triethylsilyloxy)silane Chemical compound CC[Si](CC)(CC)O[Si](CC)(CC)CC WILBTFWIBAOWLN-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 150000003573 thiols Chemical class 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 10
- 238000002360 preparation method Methods 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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 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
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 8
- 238000000746 purification 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
- 238000004440 column chromatography Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 150000001336 alkenes Chemical class 0.000 description 6
- 125000004429 atom Chemical group 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
- 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
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 6
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- TZGODTCAKVHMFG-UHFFFAOYSA-N sulfanylmethoxymethanethiol Chemical compound SCOCS TZGODTCAKVHMFG-UHFFFAOYSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 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
- LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical compound CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 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
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 239000011593 sulfur Substances 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
- 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 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
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 3
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
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- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 3
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- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
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- 229940063683 taxotere Drugs 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 150000007970 thio esters Chemical class 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 125000004665 trialkylsilyl group Chemical group 0.000 description 3
- KTSWILXIWHVQLR-UHFFFAOYSA-N tributylgermane Chemical compound CCCC[GeH](CCCC)CCCC KTSWILXIWHVQLR-UHFFFAOYSA-N 0.000 description 3
- 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Cephalosporin Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3341996P | 1996-12-24 | 1996-12-24 | |
| US60/033,419 | 1996-12-24 | ||
| US3635197P | 1997-01-23 | 1997-01-23 | |
| US60/036,351 | 1997-01-23 | ||
| PCT/US1997/022152 WO1998028288A1 (en) | 1996-12-24 | 1997-12-05 | 6-thio-substituted paclitaxels |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2268774A1 true CA2268774A1 (en) | 1998-07-02 |
Family
ID=26709670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002268774A Abandoned CA2268774A1 (en) | 1996-12-24 | 1997-12-05 | 6-thio-substituted paclitaxels |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US5977386A (enExample) |
| EP (1) | EP0960107B1 (enExample) |
| JP (1) | JP2001507029A (enExample) |
| AT (1) | ATE225341T1 (enExample) |
| AU (1) | AU722684B2 (enExample) |
| CA (1) | CA2268774A1 (enExample) |
| DE (1) | DE69716135T2 (enExample) |
| DK (1) | DK0960107T3 (enExample) |
| ES (1) | ES2184149T3 (enExample) |
| PT (1) | PT960107E (enExample) |
| WO (1) | WO1998028288A1 (enExample) |
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| JP4776843B2 (ja) | 1999-10-01 | 2011-09-21 | イムノゲン インコーポレーティッド | 免疫複合体及び化学療法剤を用いる癌治療用組成物及び方法 |
| US6362217B2 (en) | 2000-03-17 | 2002-03-26 | Bristol-Myers Squibb Company | Taxane anticancer agents |
| CA2410632A1 (en) | 2000-06-22 | 2001-12-27 | David S. Garvey | 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 |
| WO2004002468A1 (en) | 2002-06-26 | 2004-01-08 | Medigene Oncology Gmbh | Method of producing a cationic liposomal preparation comprising a lipophilic compound |
| EP1633317A4 (en) | 2003-05-16 | 2008-08-20 | Intermune Inc | Synthetic chemokine receptor ligands and methods of use therefor |
| US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
| US20060188508A1 (en) | 2005-02-17 | 2006-08-24 | Cohen Stanley N | Methods and compositions for modulating angiogenesis |
| AU2007228984B2 (en) | 2006-03-22 | 2012-05-03 | Syncore Biotechnology Co., Ltd | 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 |
| EP2296645B1 (en) | 2008-05-22 | 2014-11-19 | Galera Therapeutics, LLC | Combination antitumor therapy |
| EP2310507A4 (en) | 2008-07-08 | 2013-03-20 | David Gladstone Inst | METHOD AND COMPOSITIONS FOR ANGIOGENIC MODULATION |
| 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 |
| KR102165464B1 (ko) | 2012-07-19 | 2020-10-14 | 레드우드 바이오사이언스 인코포레이티드 | Cd22에 대해 특이적인 항체 및 이들의 사용 방법 |
| EP2916835A4 (en) | 2012-11-12 | 2016-07-27 | Redwood Bioscience Inc | COMPOUNDS AND METHOD FOR PRODUCING A CONJUGATE |
| KR102064230B1 (ko) | 2013-02-15 | 2020-01-13 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 키메라 항원 수용체 및 이의 이용 방법 |
| JP6410790B2 (ja) | 2013-03-14 | 2018-10-24 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | ミトコンドリアアルデヒドデヒドロゲナーゼ−２調節因子およびその使用方法 |
| CA3178867A1 (en) | 2013-11-27 | 2015-06-04 | Redwood Bioscience, Inc. | Hydrazinyl-pyrrolo compounds and methods for producing a conjugate |
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| US10654875B2 (en) | 2015-11-12 | 2020-05-19 | The Board Of Trustees Of The Leland Stanford Junior University | Cell-penetrating, guanidinium-rich oligophosphotriesters for drug and probe delivery |
| WO2017087723A1 (en) | 2015-11-19 | 2017-05-26 | The Regents Of The University Of California | Conditionally repressible immune cell receptors and methods of use thereof |
| TWI760319B (zh) | 2015-12-30 | 2022-04-11 | 杏國新藥股份有限公司 | 乳癌治療 |
| 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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| RU2758796C2 (ru) | 2016-06-01 | 2021-11-01 | Сервье Ип Юк Лимитед | Препараты полиалкиленоксид-аспарагиназы и способы их получения и применение |
| WO2017214322A1 (en) | 2016-06-08 | 2017-12-14 | Abbvie Inc. | Anti-b7-h3 antibodies and antibody drug conjugates |
| JP2019521973A (ja) | 2016-06-08 | 2019-08-08 | アッヴィ・インコーポレイテッド | 抗ｂｈ７−ｈ３抗体及び抗体薬物コンジュゲート |
| US20200002432A1 (en) | 2016-06-08 | 2020-01-02 | Abbvie Inc. | Anti-cd98 antibodies and antibody drug conjugates |
| SG11201811193TA (en) | 2016-06-08 | 2019-01-30 | Abbvie Inc | Anti-b7-h3 antibodies and antibody drug conjugates |
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| CN110003142A (zh) * | 2018-01-04 | 2019-07-12 | 深圳福山生物科技有限公司 | 一种硒氰化合物及其用途 |
| EP3746085A4 (en) | 2018-01-31 | 2022-03-09 | Galera Labs, LLC | ANTI-CANCER POLYTHERAPY BY MEANS OF A PENTAAZA MACROCYCLIC CYCLE-TYPE COMPLEX AND AN ANTI-CANCER AGENT BASED ON PLATINUM |
| US12090170B2 (en) | 2018-04-06 | 2024-09-17 | The Regents Of The University Of California | Methods of treating glioblastomas |
| EP3773632A4 (en) | 2018-04-06 | 2022-05-18 | The Regents of The University of California | Methods of treating egfrviii expressing glioblastomas |
| KR20210009315A (ko) | 2018-04-11 | 2021-01-26 | 오하이오 스테이트 이노베이션 파운데이션 | 안약 전달용 서방형 마이크로 입자를 이용한 방법 및 조성물 |
| EP3823674A4 (en) | 2018-07-18 | 2022-12-28 | Manzanita Pharmaceuticals, Inc. | CONJUGATES FOR DELIVERING AN ANTI-CANCER AGENT TO NERVE CELLS, METHODS OF USE AND METHODS OF PRODUCTION THEREOF |
| CN113692413A (zh) | 2019-04-02 | 2021-11-23 | 肯乔克蒂生物技术股份有限公司 | 外排泵-癌症抗原多特异性抗体以及与其相关的组合物、试剂、试剂盒和方法 |
| EP4097134A1 (en) | 2020-01-29 | 2022-12-07 | Kenjockety Biotechnology, Inc. | Anti-mdr1 antibodies and uses thereof |
| CA3182472A1 (en) | 2020-06-04 | 2021-12-09 | Kenjockety Biotechnology, Inc. | Anti-abcg2 antibodies and uses thereof |
| CN116529267A (zh) | 2020-06-04 | 2023-08-01 | 肯乔克蒂生物技术股份有限公司 | Abcg2外排泵-癌症抗原多特异性抗体及其相关组合物、试剂、试剂盒和方法 |
| US20230272117A1 (en) | 2020-09-02 | 2023-08-31 | Kenjockety Biotechnology, Inc. | Anti abcc1 antibodies and uses thereof |
| WO2022103603A1 (en) | 2020-11-13 | 2022-05-19 | Kenjockety Biotechnology, Inc. | 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 |
| CA3238353A1 (en) | 2021-12-13 | 2023-06-22 | William Robert ARATHOON | 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 |
| AU663732B2 (en) * | 1991-09-23 | 1995-10-19 | Bristol-Myers Squibb Company | 10-desacetoxytaxol derivatives |
| US5272171A (en) * | 1992-02-13 | 1993-12-21 | Bristol-Myers Squibb Company | Phosphonooxy and carbonate derivatives of taxol |
| DE69325454T2 (de) * | 1992-04-17 | 2000-01-20 | Abbott Laboratories, Abbott Park | Taxol-derivate |
| US5294637A (en) * | 1992-07-01 | 1994-03-15 | Bristol-Myers Squibb Company | Fluoro taxols |
| US5254580A (en) * | 1993-01-19 | 1993-10-19 | Bristol-Myers Squibb Company | 7,8-cyclopropataxanes |
| 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 |
| HU0203995D0 (en) * | 1992-12-23 | 2003-04-28 | Bristol Myers Squibb Co | Oxazole derivatives for synthesis of sidechain-bearing taxanes and preparation thereof |
| CA2111527C (en) * | 1992-12-24 | 2000-07-18 | Jerzy Golik | Phosphonooxymethyl ethers of taxane derivatives |
| DK0687260T3 (da) * | 1993-03-05 | 2003-06-10 | Univ Florida State | Fremgangsmåde til fremstillingen af 9-desoxotaxaner |
| US5703247A (en) * | 1993-03-11 | 1997-12-30 | Virginia Tech Intellectual Properties, Inc. | 2-Debenzoyl-2-acyl taxol derivatives and methods for making same |
| EP0703909B1 (en) * | 1993-06-11 | 2000-04-26 | PHARMACIA & UPJOHN COMPANY | Delta 6,7 -taxols antineoplastic use and pharmaceutical compositions containing them |
| CA2192373A1 (en) * | 1994-06-09 | 1995-12-14 | Hirofumi Terasawa | Deacetoxytaxol derivative |
| WO1996000724A1 (en) * | 1994-06-28 | 1996-01-11 | Pharmacia & Upjohn Company | 7-ether-taxol analogs, antineoplastic use and pharmaceutical compositions containing them |
| RO116549B1 (ro) * | 1994-07-26 | 2001-03-30 | Indena Spa | Derivati de taxan, procedeu pentru prepararea acestora, intermediar pentru prepararea acestora si compozitie farmaceutica care ii contine |
-
1997
- 1997-11-26 US US08/979,139 patent/US5977386A/en not_active Expired - Fee Related
- 1997-12-05 EP EP97954044A patent/EP0960107B1/en not_active Expired - Lifetime
- 1997-12-05 ES ES97954044T patent/ES2184149T3/es not_active Expired - Lifetime
- 1997-12-05 PT PT97954044T patent/PT960107E/pt unknown
- 1997-12-05 CA CA002268774A patent/CA2268774A1/en not_active Abandoned
- 1997-12-05 JP JP52877098A patent/JP2001507029A/ja not_active Abandoned
- 1997-12-05 DE DE69716135T patent/DE69716135T2/de not_active Expired - Fee Related
- 1997-12-05 AU AU57922/98A patent/AU722684B2/en not_active Ceased
- 1997-12-05 DK DK97954044T patent/DK0960107T3/da active
- 1997-12-05 WO PCT/US1997/022152 patent/WO1998028288A1/en not_active Ceased
- 1997-12-05 AT AT97954044T patent/ATE225341T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0960107A1 (en) | 1999-12-01 |
| EP0960107B1 (en) | 2002-10-02 |
| DE69716135D1 (en) | 2002-11-07 |
| EP0960107A4 (enExample) | 1999-12-01 |
| JP2001507029A (ja) | 2001-05-29 |
| US5977386A (en) | 1999-11-02 |
| PT960107E (pt) | 2003-02-28 |
| AU5792298A (en) | 1998-07-17 |
| AU722684B2 (en) | 2000-08-10 |
| ES2184149T3 (es) | 2003-04-01 |
| ATE225341T1 (de) | 2002-10-15 |
| DK0960107T3 (da) | 2003-02-10 |
| WO1998028288A1 (en) | 1998-07-02 |
| DE69716135T2 (de) | 2003-06-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |