ES2327803T3 - Derivados de 12,13-ciclopropano epotilona. - Google Patents
Derivados de 12,13-ciclopropano epotilona. Download PDFInfo
- Publication number
- ES2327803T3 ES2327803T3 ES99915273T ES99915273T ES2327803T3 ES 2327803 T3 ES2327803 T3 ES 2327803T3 ES 99915273 T ES99915273 T ES 99915273T ES 99915273 T ES99915273 T ES 99915273T ES 2327803 T3 ES2327803 T3 ES 2327803T3
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- Prior art keywords
- alkyl
- substituted
- aryl
- group
- refers
- 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.)
- Expired - Lifetime
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- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 98
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 60
- -1 2-methyl-4-thiazolyl Chemical group 0.000 claims abstract description 53
- 125000003118 aryl group Chemical group 0.000 claims abstract description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 29
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 125000001424 substituent group Chemical group 0.000 claims abstract description 19
- 239000000460 chlorine Chemical group 0.000 claims abstract description 18
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 14
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 13
- 125000005843 halogen group Chemical group 0.000 claims abstract description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 150000002367 halogens Chemical class 0.000 claims abstract description 11
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims abstract description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 6
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims abstract description 6
- 125000001769 aryl amino group Chemical group 0.000 claims abstract description 6
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 6
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 6
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims abstract description 6
- 125000005366 cycloalkylthio group Chemical group 0.000 claims abstract description 6
- 125000004476 heterocycloamino group Chemical group 0.000 claims abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 6
- 125000003396 thiol group Chemical class [H]S* 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims abstract description 5
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 4
- 150000004677 hydrates Chemical class 0.000 claims abstract description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 239000012453 solvate Substances 0.000 claims abstract description 4
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims abstract description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000002252 acyl group Chemical group 0.000 claims abstract description 3
- 150000001412 amines Chemical class 0.000 claims abstract description 3
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims abstract description 3
- 125000005239 aroylamino group Chemical group 0.000 claims abstract description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 3
- 125000005110 aryl thio group Chemical group 0.000 claims abstract description 3
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims abstract description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 3
- 239000011737 fluorine Substances 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 125000004470 heterocyclooxy group Chemical group 0.000 claims abstract description 3
- 239000011630 iodine Chemical group 0.000 claims abstract description 3
- 229910052740 iodine Chemical group 0.000 claims abstract description 3
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- 239000011593 sulfur Substances 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 3
- 239000004593 Epoxy Chemical group 0.000 claims abstract 2
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 208000032467 Aplastic anaemia Diseases 0.000 claims description 4
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 208000030507 AIDS Diseases 0.000 claims description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 201000004569 Blindness Diseases 0.000 claims description 3
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 3
- 230000006793 arrhythmia Effects 0.000 claims description 3
- 206010003119 arrhythmia Diseases 0.000 claims description 3
- 208000014951 hematologic disease Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 210000001525 retina Anatomy 0.000 claims description 3
- 201000009890 sinusitis Diseases 0.000 claims description 3
- 239000003053 toxin Substances 0.000 claims description 3
- 231100000765 toxin Toxicity 0.000 claims description 3
- 230000009385 viral infection Effects 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 206010058019 Cancer Pain Diseases 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 208000017169 kidney disease Diseases 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 208000019423 liver disease Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims 3
- 206010038490 Renal pain Diseases 0.000 claims 2
- 206010063837 Reperfusion injury Diseases 0.000 claims 2
- 230000003412 degenerative effect Effects 0.000 claims 2
- 108700012359 toxins Proteins 0.000 claims 2
- 230000001363 autoimmune Effects 0.000 claims 1
- 125000004069 aziridinyl group Chemical group 0.000 claims 1
- 208000037906 ischaemic injury Diseases 0.000 claims 1
- 230000007654 ischemic lesion Effects 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 210000002346 musculoskeletal system Anatomy 0.000 claims 1
- 230000000626 neurodegenerative effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 150000001541 aziridines Chemical class 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 abstract 1
- 125000001153 fluoro group Chemical group F* 0.000 abstract 1
- 125000001183 hydrocarbyl group Chemical group 0.000 abstract 1
- 102200084288 rs375181336 Human genes 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 229940126062 Compound A Drugs 0.000 description 8
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 229930013356 epothilone Natural products 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 239000007832 Na2SO4 Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical compound C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 4
- OADTZFQWKOAHJF-UHFFFAOYSA-N C=1/C(CCCC(CCCCCCCCCC1)=O)=O Chemical compound C=1/C(CCCC(CCCCCCCCCC1)=O)=O OADTZFQWKOAHJF-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 102000029749 Microtubule Human genes 0.000 description 4
- 108091022875 Microtubule Proteins 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 4
- LZWPOLSJFGLQCE-UHFFFAOYSA-N heptadecane-5,9-dione Chemical compound CCCCCCCCC(=O)CCCC(=O)CCCC LZWPOLSJFGLQCE-UHFFFAOYSA-N 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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- 150000003883 epothilone derivatives Chemical class 0.000 description 3
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- 238000006116 polymerization reaction Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RGDPYGJFXILIQP-UHFFFAOYSA-N 1,1-dibromocyclopropane Chemical compound BrC1(Br)CC1 RGDPYGJFXILIQP-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
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- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 2
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- XOZIUKBZLSUILX-UHFFFAOYSA-N desoxyepothilone B Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC(C)=CCC1C(C)=CC1=CSC(C)=N1 XOZIUKBZLSUILX-UHFFFAOYSA-N 0.000 description 2
- QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 2
- XOZIUKBZLSUILX-GIQCAXHBSA-N epothilone D Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 XOZIUKBZLSUILX-GIQCAXHBSA-N 0.000 description 2
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000004589 thienofuryl group Chemical group O1C(=CC2=C1C=CS2)* 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 description 1
- ZCAGUOCUDGWENZ-UHFFFAOYSA-N thiomorpholinyl sulfoxide group Chemical group N1(CCSCC1)S(=O)N1CCSCC1 ZCAGUOCUDGWENZ-UHFFFAOYSA-N 0.000 description 1
- ZWYDDDAMNQQZHD-UHFFFAOYSA-L titanium(ii) chloride Chemical compound [Cl-].[Cl-].[Ti+2] ZWYDDDAMNQQZHD-UHFFFAOYSA-L 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- STMPXDBGVJZCEX-UHFFFAOYSA-N triethylsilyl trifluoromethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F STMPXDBGVJZCEX-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8256498P | 1998-04-21 | 1998-04-21 | |
| US82564P | 1998-04-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2327803T3 true ES2327803T3 (es) | 2009-11-03 |
Family
ID=22171978
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99915273T Expired - Lifetime ES2327803T3 (es) | 1998-04-21 | 1999-04-05 | Derivados de 12,13-ciclopropano epotilona. |
| ES99916383T Expired - Lifetime ES2273484T3 (es) | 1998-04-21 | 1999-04-05 | Derivados de epotilona modificados en 12,13. |
| ES05015236T Expired - Lifetime ES2400049T3 (es) | 1998-04-21 | 1999-04-05 | Derivados de epotilona modificados en 12,13 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99916383T Expired - Lifetime ES2273484T3 (es) | 1998-04-21 | 1999-04-05 | Derivados de epotilona modificados en 12,13. |
| ES05015236T Expired - Lifetime ES2400049T3 (es) | 1998-04-21 | 1999-04-05 | Derivados de epotilona modificados en 12,13 |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US6380395B1 (enExample) |
| EP (3) | EP1073648B1 (enExample) |
| JP (2) | JP4476483B2 (enExample) |
| CN (1) | CN1142923C (enExample) |
| AR (2) | AR015774A1 (enExample) |
| AT (2) | ATE435861T1 (enExample) |
| AU (2) | AU748526B2 (enExample) |
| BR (1) | BR9909795A (enExample) |
| CA (2) | CA2323609A1 (enExample) |
| CY (2) | CY1105836T1 (enExample) |
| DE (2) | DE69933287T2 (enExample) |
| DK (3) | DK1073647T3 (enExample) |
| ES (3) | ES2327803T3 (enExample) |
| PE (1) | PE20000460A1 (enExample) |
| PT (3) | PT1073647E (enExample) |
| TR (1) | TR200003036T2 (enExample) |
| WO (2) | WO1999054319A1 (enExample) |
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| US20050043376A1 (en) * | 1996-12-03 | 2005-02-24 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6204388B1 (en) | 1996-12-03 | 2001-03-20 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| JP4579351B2 (ja) * | 1996-12-03 | 2010-11-10 | スローン−ケッタリング インスティトュート フォア キャンサー リサーチ | エポチロンの合成とその中間体及びその類似物並びにその使用 |
| GB9810659D0 (en) | 1998-05-18 | 1998-07-15 | Ciba Geigy Ag | Organic compounds |
| DE19826988A1 (de) * | 1998-06-18 | 1999-12-23 | Biotechnolog Forschung Gmbh | Epothilon-Nebenkomponenten |
| US6410301B1 (en) | 1998-11-20 | 2002-06-25 | Kosan Biosciences, Inc. | Myxococcus host cells for the production of epothilones |
| KR100716272B1 (ko) | 1998-11-20 | 2007-05-09 | 코산 바이오사이언시즈, 인코포레이티드 | 에포틸론 및 에포틸론 유도체의 생산을 위한 재조합 방법 및 물질 |
| KR20010086073A (ko) * | 1998-12-02 | 2001-09-07 | 데이비드 존 우드 | ｐ53계 단백질의 배좌 안정성을 회복하기 위한 방법 및조성물 |
| US6780620B1 (en) * | 1998-12-23 | 2004-08-24 | Bristol-Myers Squibb Company | Microbial transformation method for the preparation of an epothilone |
| US20020058286A1 (en) * | 1999-02-24 | 2002-05-16 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| KR20020005639A (ko) * | 1999-03-29 | 2002-01-17 | 스티븐 비. 데이비스 | 옥시라닐 에포틸론으로부터 아지리디닐 에포틸론의 제조방법 |
| EP1169038B9 (en) | 1999-04-15 | 2013-07-10 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| US7125875B2 (en) | 1999-04-15 | 2006-10-24 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| US6593115B2 (en) * | 2000-03-24 | 2003-07-15 | Bristol-Myers Squibb Co. | Preparation of epothilone intermediates |
| CA2425828A1 (en) | 2000-10-13 | 2002-04-18 | The University Of Mississippi | Synthesis of epothilones and related analogs |
| AU2002245296B2 (en) * | 2001-01-25 | 2006-12-21 | Bristol-Myers Squibb Company | Methods of administering epothilone analogs for the treatment of cancer |
| JP2004521122A (ja) * | 2001-01-25 | 2004-07-15 | ブリストル−マイヤーズ スクイブ カンパニー | エポチロン類似体の非経口製剤 |
| NZ526871A (en) | 2001-01-25 | 2006-01-27 | Bristol Myers Squibb Co | Pharmaceutical dosage forms of epothilones for oral administration |
| BRPI0206509B8 (pt) * | 2001-01-25 | 2021-05-25 | R Pharm Us Operating Llc | processo para formular, para administração parenteral, um análogo de epotilona, preparação farmacêutica, processo para formar uma composição farmacêutica para administração parental, composição farmacêutica e uso de um análogo de epotilona na preparação de uma composição farmacêutica para o tratamento de câncer |
| CA2438610A1 (en) | 2001-02-20 | 2002-08-29 | Francis Y. F. Lee | Treatment of refractory tumors using epothilone derivatives |
| MXPA03007423A (es) | 2001-02-20 | 2003-11-18 | Bristol Myers Squibb Co | Derivados de epotilona para tratamiento de tumores refractarios. |
| CZ305799B6 (cs) * | 2001-03-14 | 2016-03-23 | Bristol-Myers Squibb Company | Kombinace analogů epothilonu a chemoterapeutických činidel pro léčení proliferačních nemocí |
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| EP1392664A4 (en) * | 2001-06-01 | 2005-01-26 | Bristol Myers Squibb Co | EPOTHILONE DERIVATIVES |
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| WO2003077903A1 (en) * | 2002-03-12 | 2003-09-25 | Bristol-Myers Squibb Company | C12-cyano epothilone derivatives |
| ATE452896T1 (de) | 2002-03-12 | 2010-01-15 | Bristol Myers Squibb Co | C3-cyanoepothilonderivate |
| TW200403994A (en) | 2002-04-04 | 2004-03-16 | Bristol Myers Squibb Co | Oral administration of EPOTHILONES |
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| US6921769B2 (en) | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| CA2496477C (en) * | 2002-08-23 | 2012-10-16 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US7649006B2 (en) * | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
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1999
- 1999-03-29 US US09/280,192 patent/US6380395B1/en not_active Expired - Lifetime
- 1999-03-29 US US09/280,191 patent/US6399638B1/en not_active Expired - Lifetime
- 1999-04-05 PT PT99915273T patent/PT1073647E/pt unknown
- 1999-04-05 WO PCT/US1999/007475 patent/WO1999054319A1/en not_active Ceased
- 1999-04-05 AU AU34716/99A patent/AU748526B2/en not_active Ceased
- 1999-04-05 CA CA002323609A patent/CA2323609A1/en not_active Abandoned
- 1999-04-05 CA CA2329181A patent/CA2329181C/en not_active Expired - Fee Related
- 1999-04-05 EP EP99916383A patent/EP1073648B1/en not_active Expired - Lifetime
- 1999-04-05 WO PCT/US1999/007448 patent/WO1999054318A1/en not_active Ceased
- 1999-04-05 DE DE69933287T patent/DE69933287T2/de not_active Expired - Lifetime
- 1999-04-05 ES ES99915273T patent/ES2327803T3/es not_active Expired - Lifetime
- 1999-04-05 TR TR2000/03036T patent/TR200003036T2/xx unknown
- 1999-04-05 DK DK99915273T patent/DK1073647T3/da active
- 1999-04-05 JP JP2000544658A patent/JP4476483B2/ja not_active Expired - Fee Related
- 1999-04-05 DK DK05015236.2T patent/DK1589017T3/da active
- 1999-04-05 EP EP99915273A patent/EP1073647B1/en not_active Expired - Lifetime
- 1999-04-05 ES ES99916383T patent/ES2273484T3/es not_active Expired - Lifetime
- 1999-04-05 BR BR9909795-8A patent/BR9909795A/pt not_active IP Right Cessation
- 1999-04-05 PT PT99916383T patent/PT1073648E/pt unknown
- 1999-04-05 AT AT99915273T patent/ATE435861T1/de active
- 1999-04-05 DK DK99916383T patent/DK1073648T3/da active
- 1999-04-05 DE DE69941083T patent/DE69941083D1/de not_active Expired - Lifetime
- 1999-04-05 JP JP2000544657A patent/JP2002512238A/ja active Pending
- 1999-04-05 AU AU33827/99A patent/AU757733B2/en not_active Ceased
- 1999-04-05 CN CNB998052663A patent/CN1142923C/zh not_active Expired - Fee Related
- 1999-04-05 EP EP05015236A patent/EP1589017B1/en not_active Expired - Lifetime
- 1999-04-05 PT PT50152362T patent/PT1589017E/pt unknown
- 1999-04-05 ES ES05015236T patent/ES2400049T3/es not_active Expired - Lifetime
- 1999-04-05 AT AT99916383T patent/ATE340177T1/de active
- 1999-04-20 PE PE1999000331A patent/PE20000460A1/es not_active Application Discontinuation
- 1999-04-21 AR ARP990101834A patent/AR015774A1/es unknown
- 1999-04-21 AR ARP990101833A patent/AR015007A1/es unknown
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2006
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2009
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