UA80409C2 - Hexacyclic compounds - Google Patents
Hexacyclic compounds Download PDFInfo
- Publication number
- UA80409C2 UA80409C2 UA20040605013A UA20040605013A UA80409C2 UA 80409 C2 UA80409 C2 UA 80409C2 UA 20040605013 A UA20040605013 A UA 20040605013A UA 20040605013 A UA20040605013 A UA 20040605013A UA 80409 C2 UA80409 C2 UA 80409C2
- Authority
- UA
- Ukraine
- Prior art keywords
- ethyl
- hydroxy
- pyrano
- dione
- quinazoline
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 314
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 191
- 238000002360 preparation method Methods 0.000 claims description 126
- -1 p-propyl Chemical group 0.000 claims description 115
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 38
- 125000003282 alkyl amino group Chemical group 0.000 claims description 37
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 150000002367 halogens Chemical class 0.000 claims description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 206010028980 Neoplasm Diseases 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 201000011510 cancer Diseases 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 12
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 11
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 229910052717 sulfur Chemical group 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- 125000001589 carboacyl group Chemical group 0.000 claims description 9
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 7
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 230000004663 cell proliferation Effects 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 208000035475 disorder Diseases 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 108091000080 Phosphotransferase Proteins 0.000 claims description 6
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 102000020233 phosphotransferase Human genes 0.000 claims description 6
- 206010038038 rectal cancer Diseases 0.000 claims description 6
- 201000001275 rectum cancer Diseases 0.000 claims description 6
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 229940126601 medicinal product Drugs 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- 201000010881 cervical cancer Diseases 0.000 claims description 4
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 230000020176 deacylation Effects 0.000 claims description 2
- 238000005947 deacylation reaction Methods 0.000 claims description 2
- 238000007911 parenteral administration Methods 0.000 claims description 2
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- 150000001923 cyclic compounds Chemical class 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000005059 halophenyl group Chemical group 0.000 claims 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
- ASVIEXKOXDCZDF-QFIPXVFZSA-N 1v364427ug Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(OC(C)=O)CC)C4=NC2=C1 ASVIEXKOXDCZDF-QFIPXVFZSA-N 0.000 description 91
- 238000005481 NMR spectroscopy Methods 0.000 description 90
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- 229950009213 rubitecan Drugs 0.000 description 60
- 239000000203 mixture Substances 0.000 description 50
- 239000000243 solution Substances 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 238000004440 column chromatography Methods 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 239000000047 product Substances 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 229940127093 camptothecin Drugs 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 6
- 239000007903 gelatin capsule Substances 0.000 description 6
- 150000007522 mineralic acids Chemical class 0.000 description 6
- 150000007524 organic acids Chemical class 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-N 0.000 description 5
- 102000003915 DNA Topoisomerases Human genes 0.000 description 5
- 108090000323 DNA Topoisomerases Proteins 0.000 description 5
- 229910052770 Uranium Inorganic materials 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
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- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 125000006715 (C1-C5) alkylthio group Chemical group 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
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- 238000002347 injection Methods 0.000 description 4
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
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- 210000004881 tumor cell Anatomy 0.000 description 4
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- 125000003277 amino group Chemical group 0.000 description 3
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- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
- 125000002757 morpholinyl group Chemical group 0.000 description 3
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- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 3
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- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 2
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 2
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
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- LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 description 2
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 2
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
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- 150000002739 metals Chemical class 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 208000033937 musculocontractural type Ehlers-Danlos syndrome Diseases 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
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- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012766 organic filler Substances 0.000 description 1
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- 230000003204 osmotic effect Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
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- JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 108091005981 phosphorylated proteins Proteins 0.000 description 1
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- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
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- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
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- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
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- 238000013207 serial dilution Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
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- 238000010254 subcutaneous injection Methods 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- AHJWSRRHTXRLAQ-UHFFFAOYSA-N tetramethoxymethane Chemical compound COC(OC)(OC)OC AHJWSRRHTXRLAQ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
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- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
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- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Natural products NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 1
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- 206010046766 uterine cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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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
- C07D491/22—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 four or more hetero rings
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01128361 | 2001-11-30 | ||
| PCT/EP2002/013216 WO2003045952A2 (en) | 2001-11-30 | 2002-11-25 | Condensed camptothecins as antitumor agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA80409C2 true UA80409C2 (en) | 2007-09-25 |
Family
ID=8179394
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA20040605013A UA80409C2 (en) | 2001-11-30 | 2002-11-25 | Hexacyclic compounds |
Country Status (29)
| Country | Link |
|---|---|
| US (2) | US6825194B2 (ja) |
| EP (1) | EP1480984B9 (ja) |
| JP (1) | JP4305909B2 (ja) |
| KR (1) | KR100895746B1 (ja) |
| CN (1) | CN100338066C (ja) |
| AT (1) | ATE398131T1 (ja) |
| AU (1) | AU2002356720B2 (ja) |
| BR (1) | BR0214615A (ja) |
| CA (1) | CA2468824C (ja) |
| DE (1) | DE60227113D1 (ja) |
| ES (1) | ES2307830T3 (ja) |
| GT (1) | GT200200250A (ja) |
| HK (2) | HK1072935A1 (ja) |
| HU (1) | HUP0500062A3 (ja) |
| IL (1) | IL162058A0 (ja) |
| MX (1) | MXPA04005185A (ja) |
| MY (1) | MY136138A (ja) |
| NO (1) | NO329005B1 (ja) |
| NZ (1) | NZ533568A (ja) |
| PA (1) | PA8558901A1 (ja) |
| PE (1) | PE20030725A1 (ja) |
| PL (1) | PL207510B1 (ja) |
| RS (1) | RS51051B (ja) |
| RU (1) | RU2299212C2 (ja) |
| TW (1) | TWI258481B (ja) |
| UA (1) | UA80409C2 (ja) |
| UY (1) | UY27560A1 (ja) |
| WO (1) | WO2003045952A2 (ja) |
| ZA (1) | ZA200404522B (ja) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1599484A2 (en) * | 2003-02-21 | 2005-11-30 | Chugai Seiyaku Kabushiki Kaisha | Process for the preparation of hexacyclic camptothecin derivatives |
| CN1964979B (zh) | 2004-04-09 | 2011-07-27 | 中外制药株式会社 | 新颖的水溶性前药 |
| TW200744603A (en) | 2005-08-22 | 2007-12-16 | Chugai Pharmaceutical Co Ltd | Novel anticancer concomitant drug |
| CA2626330A1 (en) * | 2005-10-19 | 2007-04-26 | Chugai Seiyaku Kabushiki Kaisha | Preventive or therapeutic agents for pancreatic cancer, ovarian cancer, or liver cancer comprising a novel water-solube prodrug |
| EP4176904A1 (en) | 2019-03-29 | 2023-05-10 | MedImmune Limited | Compounds and conjugates thereof |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4473692A (en) | 1981-09-04 | 1984-09-25 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives and process for preparing same |
| US4939255A (en) * | 1987-06-24 | 1990-07-03 | Daiichi Pharmaceutical Co., Ltd. | Hexa-cyclic camptothecin derivatives |
| HU213136B (en) * | 1990-08-14 | 1997-02-28 | Kyorin Seiyaku Kk | Process for producing fluoroethyl camptothecin derivatives and pharmaceutical compositions containing them |
| JP3008226B2 (ja) * | 1991-01-16 | 2000-02-14 | 第一製薬株式会社 | 六環性化合物 |
| JP3359955B2 (ja) * | 1992-07-16 | 2002-12-24 | 第一製薬株式会社 | 抗腫瘍剤 |
| GB9402934D0 (en) * | 1994-02-16 | 1994-04-06 | Erba Carlo Spa | Camptothecin derivatives and process for their preparation |
| US5663177A (en) * | 1995-05-31 | 1997-09-02 | Smithkline Beecham Corporation | Water soluble camptothecin analogs |
| EP1017675B1 (en) | 1997-02-14 | 2006-06-14 | Bionumerik Pharmaceuticals, Inc. | Highly lipophilic camptothecin derivatives |
| GB9715821D0 (en) * | 1997-07-25 | 1997-10-01 | Pharmacia & Upjohn Spa | Amidino-camptothecin derivatives |
-
2002
- 2002-11-25 CN CNB028277465A patent/CN100338066C/zh not_active Expired - Fee Related
- 2002-11-25 ES ES02803790T patent/ES2307830T3/es not_active Expired - Lifetime
- 2002-11-25 DE DE60227113T patent/DE60227113D1/de not_active Expired - Lifetime
- 2002-11-25 JP JP2003547402A patent/JP4305909B2/ja not_active Expired - Fee Related
- 2002-11-25 MX MXPA04005185A patent/MXPA04005185A/es active IP Right Grant
- 2002-11-25 BR BR0214615-0A patent/BR0214615A/pt not_active IP Right Cessation
- 2002-11-25 RS YUP-470/04A patent/RS51051B/sr unknown
- 2002-11-25 CA CA2468824A patent/CA2468824C/en not_active Expired - Fee Related
- 2002-11-25 NZ NZ533568A patent/NZ533568A/en not_active IP Right Cessation
- 2002-11-25 HU HU0500062A patent/HUP0500062A3/hu unknown
- 2002-11-25 AT AT02803790T patent/ATE398131T1/de not_active IP Right Cessation
- 2002-11-25 PL PL370479A patent/PL207510B1/pl not_active IP Right Cessation
- 2002-11-25 EP EP02803790A patent/EP1480984B9/en not_active Expired - Lifetime
- 2002-11-25 WO PCT/EP2002/013216 patent/WO2003045952A2/en active IP Right Grant
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- 2002-11-25 IL IL16205802A patent/IL162058A0/xx not_active IP Right Cessation
- 2002-11-25 AU AU2002356720A patent/AU2002356720B2/en not_active Ceased
- 2002-11-25 UA UA20040605013A patent/UA80409C2/uk unknown
- 2002-11-25 KR KR1020047008223A patent/KR100895746B1/ko not_active IP Right Cessation
- 2002-11-26 US US10/304,672 patent/US6825194B2/en not_active Expired - Fee Related
- 2002-11-27 TW TW091134463A patent/TWI258481B/zh not_active IP Right Cessation
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2004
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