CN1027169C - 表鬼臼毒葡糖苷4′-磷酸酯衍生物的制备方法 - Google Patents
表鬼臼毒葡糖苷4′-磷酸酯衍生物的制备方法 Download PDFInfo
- Publication number
- CN1027169C CN1027169C CN91108384A CN91108384A CN1027169C CN 1027169 C CN1027169 C CN 1027169C CN 91108384 A CN91108384 A CN 91108384A CN 91108384 A CN91108384 A CN 91108384A CN 1027169 C CN1027169 C CN 1027169C
- Authority
- CN
- China
- Prior art keywords
- compound
- etoposide
- general formula
- glucosides
- formaldehyde
- 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
Links
- 229930182478 glucoside Natural products 0.000 title abstract description 64
- -1 epipodophyllotoxin glucoside Chemical class 0.000 title description 85
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims description 57
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 claims description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 239000005864 Sulphur Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 19
- 230000000259 anti-tumor effect Effects 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 10
- FOVRGQUEGRCWPD-UHFFFAOYSA-N (5aR)-9t-beta-D-Glucopyranosyloxy-5t-(4-hydroxy-3,5-dimethoxy-phenyl)-(5ar,8at)-5,8,8a,9-tetrahydro-5aH-furo[3',4';6,7]naphtho[2,3-d][1,3]dioxol-6-on Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(OC3C(C(O)C(O)C(CO)O3)O)C3C2C(OC3)=O)=C1 FOVRGQUEGRCWPD-UHFFFAOYSA-N 0.000 abstract 1
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 125000002467 phosphate group Chemical class [H]OP(=O)(O[H])O[*] 0.000 abstract 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 93
- 229960005420 etoposide Drugs 0.000 description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000000460 chlorine Substances 0.000 description 29
- 239000000203 mixture Substances 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- 210000000683 abdominal cavity Anatomy 0.000 description 12
- 150000003014 phosphoric acid esters Chemical class 0.000 description 12
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 229910052698 phosphorus Inorganic materials 0.000 description 10
- 239000011574 phosphorus Substances 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000008367 deionised water Substances 0.000 description 8
- 229910021641 deionized water Inorganic materials 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000001819 mass spectrum Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 238000010520 demethylation reaction Methods 0.000 description 6
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 5
- WPGUUPJOAVPZBQ-UHFFFAOYSA-N [Cl].OP(O)(O)=O Chemical compound [Cl].OP(O)(O)=O WPGUUPJOAVPZBQ-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- WVPKAWVFTPWPDB-UHFFFAOYSA-N dichlorophosphinic acid Chemical compound OP(Cl)(Cl)=O WVPKAWVFTPWPDB-UHFFFAOYSA-N 0.000 description 5
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 5
- HXBZCHYDLURWIZ-UHFFFAOYSA-N diphenyl hydrogen phosphate;hydrochloride Chemical compound Cl.C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 HXBZCHYDLURWIZ-UHFFFAOYSA-N 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 230000017858 demethylation Effects 0.000 description 4
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 4
- 238000011081 inoculation Methods 0.000 description 4
- QHCCDDQKNUYGNC-UHFFFAOYSA-N n-ethylbutan-1-amine Chemical compound CCCCNCC QHCCDDQKNUYGNC-UHFFFAOYSA-N 0.000 description 4
- 150000003053 piperidines Chemical class 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
- VKPPFDPXZWFDFA-UHFFFAOYSA-N 2-chloroethanamine Chemical compound NCCCl VKPPFDPXZWFDFA-UHFFFAOYSA-N 0.000 description 3
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 3
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 3
- UNIJBMUBHBAUET-UHFFFAOYSA-N 3-(methylamino)propanenitrile Chemical compound CNCCC#N UNIJBMUBHBAUET-UHFFFAOYSA-N 0.000 description 3
- 238000004679 31P NMR spectroscopy Methods 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KGWDUNBJIMUFAP-KVVVOXFISA-N Ethanolamine Oleate Chemical compound NCCO.CCCCCCCC\C=C/CCCCCCCC(O)=O KGWDUNBJIMUFAP-KVVVOXFISA-N 0.000 description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 150000008131 glucosides Chemical class 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 description 3
- DAKZISABEDGGSV-UHFFFAOYSA-N n-(2-aminoethyl)acetamide Chemical compound CC(=O)NCCN DAKZISABEDGGSV-UHFFFAOYSA-N 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000001294 propane Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000007738 vacuum evaporation Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000000118 anti-neoplastic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003729 cation exchange resin Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- DJMIKAGANCZWLL-UHFFFAOYSA-N dihydroxy hydrogen phosphate Chemical compound OOP(O)(=O)OO DJMIKAGANCZWLL-UHFFFAOYSA-N 0.000 description 2
- ASMQGLCHMVWBQR-UHFFFAOYSA-M diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)([O-])OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-M 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 2
- 229960000752 etoposide phosphate Drugs 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000002831 pharmacologic agent Substances 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000002769 thiazolinyl group Chemical group 0.000 description 2
- WQYSXVGEZYESBR-UHFFFAOYSA-N thiophosphoryl chloride Chemical compound ClP(Cl)(Cl)=S WQYSXVGEZYESBR-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 108050008598 Phosphoesterases Proteins 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 208000033781 Thyroid carcinoma Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- XVPASMIMNOICHG-UHFFFAOYSA-N aminophosphonic acid hydrochloride Chemical compound Cl.NP(O)(O)=O XVPASMIMNOICHG-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 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 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003327 cancerostatic effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000004969 haloethyl group Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940061584 phosphoramidic acid Drugs 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 150000003017 phosphorus Chemical class 0.000 description 1
- 229910001392 phosphorus oxide Inorganic materials 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229960001237 podophyllotoxin Drugs 0.000 description 1
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000012713 reactive precursor Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- VSAISIQCTGDGPU-UHFFFAOYSA-N tetraphosphorus hexaoxide Chemical compound O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Mechanical Coupling Of Light Guides (AREA)
- Cable Accessories (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8149387A | 1987-08-04 | 1987-08-04 | |
| US081493 | 1987-08-04 | ||
| US081,493 | 1987-08-04 | ||
| US07/199,731 US4904768A (en) | 1987-08-04 | 1988-05-27 | Epipodophyllotoxin glucoside 4'-phosphate derivatives |
| US199,731 | 1988-05-27 | ||
| US199731 | 1988-05-27 | ||
| CN 88104796 CN1020615C (zh) | 1987-08-04 | 1988-08-04 | 表鬼臼毒葡糖苷4′-磷酸酯衍生物的制备方法 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 88104796 Division CN1020615C (zh) | 1987-08-04 | 1988-08-04 | 表鬼臼毒葡糖苷4′-磷酸酯衍生物的制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1061225A CN1061225A (zh) | 1992-05-20 |
| CN1027169C true CN1027169C (zh) | 1994-12-28 |
Family
ID=26765636
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN91108384A Expired - Lifetime CN1027169C (zh) | 1987-08-04 | 1991-10-30 | 表鬼臼毒葡糖苷4′-磷酸酯衍生物的制备方法 |
Country Status (34)
| Country | Link |
|---|---|
| US (3) | US4904768A (show.php) |
| JP (1) | JPH0699465B2 (show.php) |
| KR (1) | KR900006230B1 (show.php) |
| CN (1) | CN1027169C (show.php) |
| AT (1) | AT398974B (show.php) |
| BE (1) | BE1002982A4 (show.php) |
| CA (1) | CA1310637C (show.php) |
| CH (1) | CH676716A5 (show.php) |
| CY (1) | CY1625A (show.php) |
| CZ (1) | CZ286893B6 (show.php) |
| DD (2) | DD299067A5 (show.php) |
| DE (1) | DE3826562A1 (show.php) |
| DK (2) | DK169344B1 (show.php) |
| ES (1) | ES2010775A6 (show.php) |
| FI (1) | FI87790C (show.php) |
| FR (1) | FR2622193B1 (show.php) |
| GB (1) | GB2207674B (show.php) |
| GR (1) | GR1000490B (show.php) |
| HK (1) | HK6392A (show.php) |
| HU (3) | HU208147B (show.php) |
| IE (1) | IE61040B1 (show.php) |
| IL (1) | IL87290A (show.php) |
| IT (1) | IT1226825B (show.php) |
| LU (2) | LU87290A1 (show.php) |
| MX (1) | MX173843B (show.php) |
| MY (1) | MY104321A (show.php) |
| NL (2) | NL192683C (show.php) |
| NO (4) | NO170284C (show.php) |
| NZ (1) | NZ225615A (show.php) |
| PT (1) | PT88186B (show.php) |
| SE (1) | SE502214C2 (show.php) |
| SG (1) | SG101291G (show.php) |
| SK (1) | SK541288A3 (show.php) |
| YU (3) | YU143688A (show.php) |
Families Citing this family (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5191071A (en) * | 1987-08-21 | 1993-03-02 | Novo Nordisk A/S | Monoesters of glycosides and a process for enzymatic preparation thereof |
| US4965348A (en) * | 1989-05-19 | 1990-10-23 | Bristol-Myers Company | Dimeric epipodophyllotoxin glucoside derivatives |
| US5036055A (en) * | 1989-06-07 | 1991-07-30 | Bristol-Myers Company | Acylated derivatives of etoposide |
| US5066645A (en) * | 1989-09-01 | 1991-11-19 | Bristol-Myers Company | Epipodophyllotoxin altroside derivatives |
| US6610299B1 (en) | 1989-10-19 | 2003-08-26 | Aventis Pharma Deutschland Gmbh | Glycosyl-etoposide prodrugs, a process for preparation thereof and the use thereof in combination with functionalized tumor-specific enzyme conjugates |
| US6475486B1 (en) | 1990-10-18 | 2002-11-05 | Aventis Pharma Deutschland Gmbh | Glycosyl-etoposide prodrugs, a process for preparation thereof and the use thereof in combination with functionalized tumor-specific enzyme conjugates |
| US7241595B2 (en) | 1989-10-20 | 2007-07-10 | Sanofi-Aventis Pharma Deutschland Gmbh | Glycosyl-etoposide prodrugs, a process for preparation thereof and the use thereof in combination with functionalized tumor-specific enzyme conjugates |
| US5552154A (en) * | 1989-11-06 | 1996-09-03 | The Stehlin Foundation For Cancer Research | Method for treating cancer with water-insoluble s-camptothecin of the closed lactone ring form and derivatives thereof |
| US5034380A (en) * | 1989-11-20 | 1991-07-23 | Bristol-Myers Squibb Company | Alkoxymethylidene epipodophyllotoxin glucosides |
| US5081234A (en) * | 1990-04-30 | 1992-01-14 | Bristol-Myers Squibb Co. | 4'-demethylepipodophyllotoxin glycosides |
| US4997931A (en) * | 1990-06-11 | 1991-03-05 | Bristol-Myers Squibb Company | Epipodophyllotoxin glycosides |
| TW260671B (show.php) * | 1991-04-29 | 1995-10-21 | Bristol Myers Squibb Co | |
| IT1250692B (it) * | 1991-07-23 | 1995-04-21 | Procedimento per la preparazione di demetilepipodofillotossina- beta-d-glucosidi. | |
| US5648474A (en) * | 1991-10-08 | 1997-07-15 | Bristol-Myers Squibb | Crystalline etoposide 4'-phosphate diethanolate |
| CA2085520C (en) * | 1991-12-23 | 1996-07-16 | Uday Shankar Gogate | Stable hexahydrate of etoposide 4'-phosphate disodium salt |
| US6080751A (en) * | 1992-01-14 | 2000-06-27 | The Stehlin Foundation For Cancer Research | Method for treating pancreatic cancer in humans with water-insoluble S-camptothecin of the closed lactone ring form and derivatives thereof |
| JP3061476B2 (ja) * | 1992-04-24 | 2000-07-10 | 日本化薬株式会社 | エトポシド燐酸エステルの製造法 |
| US5459248A (en) * | 1993-11-04 | 1995-10-17 | Bristol-Myers Squibb Company | Process of preparing etoposide phosphate and etoposide |
| FR2725990B1 (fr) * | 1994-10-21 | 1997-01-10 | Pf Medicament | Derives hydrosolubles d'epipodophyllotoxine, leur procede de preparation, leur utilisation a titre de medicament, et leur utilisation destinee aux traitements anticancereux |
| CA2223484A1 (en) * | 1995-06-07 | 1996-12-19 | Thomas Jefferson University | Anti-fungal agents and methods of identifying and using the same |
| BR9708470A (pt) | 1996-04-01 | 1999-04-13 | Epix Medical Inc | Agentes de contraste bioativados para formação de imagem para diagnósticos |
| US6207673B1 (en) | 1997-03-12 | 2001-03-27 | The University Of North Carolina At Chapel Hill | Covalent conjugates of topoisomerase I and topoisomerase II inhibitors |
| WO1999032499A1 (en) * | 1997-12-23 | 1999-07-01 | Korea Research Institute Of Chemical Technology | 4'-O-DEMETHYL-EPIPODOPHYLLOTOXIN-β-D-GLUCOSIDE ACETAL DERIVATIVES |
| WO2001024763A2 (en) | 1999-10-01 | 2001-04-12 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| US6624317B1 (en) | 2000-09-25 | 2003-09-23 | The University Of North Carolina At Chapel Hill | Taxoid conjugates as antimitotic and antitumor agents |
| US6506739B1 (en) | 2001-05-01 | 2003-01-14 | Telik, Inc. | Bis-(N,N'-bis-(2-haloethyl)amino)phosphoramidates as antitumor agents |
| JP2005511550A (ja) * | 2001-10-26 | 2005-04-28 | サントル・ナショナル・ドゥ・ラ・ルシェルシュ・シャンティフィク | エトポシドおよび類似体の誘導体、ならびにそれを含有する医薬組成物 |
| CA2491310C (en) | 2002-07-15 | 2015-10-06 | Board Of Regents, The University Of Texas System | Compositions comprising cell-impermeant duramycin derivatives |
| EP1583562B1 (en) * | 2003-01-06 | 2011-06-15 | Angiochem Inc. | Angiopep-1, related compounds, and uses thereof |
| CN100334090C (zh) * | 2005-02-02 | 2007-08-29 | 南京医科大学 | 吡啶类鬼臼毒素化合物及其制备方法和在制备杀虫剂中的应用 |
| US20090016959A1 (en) * | 2005-02-18 | 2009-01-15 | Richard Beliveau | Delivery of antibodies to the central nervous system |
| PL2360258T3 (pl) * | 2005-02-18 | 2015-03-31 | Angiochem Inc | Polipeptydy aprotyniny do transportowania związków przez barierę krew-mózg |
| ES2424242T3 (es) | 2005-07-15 | 2013-09-30 | Angiochem Inc. | Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos |
| CN100410266C (zh) * | 2006-01-11 | 2008-08-13 | 重庆华邦制药股份有限公司 | 鬼臼毒素磷酸酯衍生物的合成方法 |
| JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| PE20070978A1 (es) * | 2006-02-14 | 2007-11-15 | Novartis Ag | COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE FOSFATIDILINOSITOL 3-QUINASAS (PI3Ks) |
| TW200808739A (en) * | 2006-04-06 | 2008-02-16 | Novartis Vaccines & Diagnostic | Quinazolines for PDK1 inhibition |
| GB0625283D0 (en) * | 2006-12-19 | 2007-01-24 | Cyclacel Ltd | Combination |
| US9365634B2 (en) * | 2007-05-29 | 2016-06-14 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| US8263644B2 (en) * | 2007-09-13 | 2012-09-11 | Bristol-Myers Squibb Company | Cytotoxic xanthone compounds |
| JP5809415B2 (ja) | 2007-11-09 | 2015-11-10 | ペレグリン ファーマシューティカルズ，インコーポレーテッド | 抗ｖｅｇｆ抗体の組成物および方法 |
| EP2240475B1 (en) | 2007-12-20 | 2013-09-25 | Novartis AG | Thiazole derivatives used as pi 3 kinase inhibitors |
| CN102026667B (zh) * | 2008-04-18 | 2014-06-25 | 安吉奥开米公司 | 紫杉醇、紫杉醇类似物或紫杉醇结合物的药物组合物及相关制备方法和用途 |
| AU2009304505A1 (en) | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Etoposide and doxorubicin conjugates for drug delivery |
| MX2011004017A (es) | 2008-10-15 | 2011-06-24 | Angiochem Inc | Conjugados de agonistas glp-1 y usos de los mismos. |
| AU2009322043A1 (en) * | 2008-12-05 | 2011-07-07 | Angiochem Inc. | Conjugates of neurotensin or neurotensin analogs and uses thereof |
| CN102300987A (zh) | 2008-12-17 | 2011-12-28 | 安吉奥开米公司 | 膜型-1基质金属蛋白抑制剂及其用途 |
| BRPI1015295A2 (pt) | 2009-04-20 | 2016-05-31 | Angiochem Inc | traamento de câncer de ovário usando um agente anticâncer conjugado a um análogo angiopep-2. |
| US8293753B2 (en) | 2009-07-02 | 2012-10-23 | Novartis Ag | Substituted 2-carboxamide cycloamino ureas |
| CA2766537A1 (en) | 2009-07-02 | 2011-01-06 | Angiochem Inc. | Multimeric peptide conjugates and uses thereof |
| BR112012019635A2 (pt) | 2010-02-22 | 2016-05-03 | Hoffmann La Roche | compostos inibidores de pirido[3,2-d] pirimidina pi3k delta e métodos de uso |
| US9586954B2 (en) | 2010-06-22 | 2017-03-07 | Demerx, Inc. | N-substituted noribogaine prodrugs |
| AR082418A1 (es) | 2010-08-02 | 2012-12-05 | Novartis Ag | Formas cristalinas de 1-(4-metil-5-[2-(2,2,2-trifluoro-1,1-dimetil-etil)-piridin-4-il]-tiazol-2-il)-amida de 2-amida del acido (s)-pirrolidin-1,2-dicarboxilico |
| WO2012104776A1 (en) | 2011-01-31 | 2012-08-09 | Novartis Ag | Novel heterocyclic derivatives |
| US9617274B1 (en) | 2011-08-26 | 2017-04-11 | Demerx, Inc. | Synthetic noribogaine |
| KR20140090218A (ko) | 2011-10-28 | 2014-07-16 | 노파르티스 아게 | 신규 퓨린 유도체 및 질환의 치료에서의 그의 용도 |
| EP2788003A4 (en) * | 2011-12-09 | 2015-05-27 | Demerx Inc | PHOSPHATESTER OF NORIBOGAIN |
| CN104349779A (zh) | 2012-05-16 | 2015-02-11 | 诺华股份有限公司 | Pi-3激酶抑制剂的剂量方案 |
| JP2016508979A (ja) | 2012-12-20 | 2016-03-24 | デメレックス， インコーポレイテッド | 置換ノルイボガイン |
| MX378409B (es) | 2013-12-06 | 2025-03-10 | Novartis Ag | Regimen de dosificacion para un inhibidor selectivo alfa-isomorfo de fosfatidilinositol 3-quinasa. |
| WO2016205367A1 (en) | 2015-06-15 | 2016-12-22 | Angiochem Inc. | Methods for the treatment of leptomeningeal carcinomatosis |
| CA3002954A1 (en) | 2015-11-02 | 2017-05-11 | Novartis Ag | Dosage regimen for a phosphatidylinositol 3-kinase inhibitor |
| WO2018060833A1 (en) | 2016-09-27 | 2018-04-05 | Novartis Ag | Dosage regimen for alpha-isoform selective phosphatidylinositol 3-kinase inhibitor alpelisib |
| KR102378151B1 (ko) | 2020-05-11 | 2022-03-24 | 주식회사 제이앤씨사이언스 | 베타-아포피크로포도필린의 신규한 유도체 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1171314A (fr) * | 1955-05-13 | 1959-01-23 | Sandoz Ag | Produits de condensation de glucosides avec des composés carbonyliques et leur préparation |
| NL6613143A (show.php) * | 1965-09-21 | 1967-03-22 | ||
| CH464957A (de) * | 1965-12-14 | 1968-11-15 | Sandoz Ag | Verfahren zur Herstellung eines neuen Glucosids |
| CH484101A (de) * | 1966-12-13 | 1970-01-15 | Sandoz Ag | Verfahren zur Herstellung neuer Glucoside |
| CH514578A (de) * | 1968-02-27 | 1971-10-31 | Sandoz Ag | Verfahren zur Herstellung von Glucosiden |
| CH543502A (de) * | 1970-11-20 | 1973-10-31 | Sandoz Ag | Verfahren zur Herstellung neuer Glucoside |
| GB1395820A (en) * | 1971-06-05 | 1975-05-29 | Villax I | Preparation of 21-inorganic esters of corticosteroids and salts thereof |
| CH589668A5 (en) * | 1973-06-07 | 1977-07-15 | Sandoz Ag | Cytostatic (4')-demethyl substd. epipodophyllotoxin - prepd. from the corresp. glucopyranoside with (3)-thiophene-carboxaldehyde |
| FR2397425A1 (fr) * | 1977-07-11 | 1979-02-09 | Rhone Poulenc Ind | Nouveaux derives de la daunorubicine, leur preparation et les compositions qui les contiennent |
| EP0111058B1 (en) * | 1982-11-26 | 1987-11-04 | Nippon Kayaku Kabushiki Kaisha | Process for producing 4'-demethyl-epipodophyllotoxin-beta-d-ethylidene-glucoside and acyl-derivative thereof |
| US4567253A (en) * | 1984-02-03 | 1986-01-28 | Tony Durst | 2-Substituted derivatives of podophyllotoxin and etoposide |
| JPS60208910A (ja) * | 1984-03-31 | 1985-10-21 | Green Cross Corp:The | 水難溶性薬物・リン脂質複合体の製造方法 |
| JPS60246393A (ja) * | 1984-05-22 | 1985-12-06 | Nippon Kayaku Co Ltd | エトポシドの新規製造法 |
| US4739046A (en) * | 1985-08-19 | 1988-04-19 | Luzio Nicholas R Di | Soluble phosphorylated glucan |
| IL77334A (en) * | 1985-12-16 | 1991-04-15 | Univ Bar Ilan | Synthesis of 9-epipodophyllotoxin glucoside derivatives and some novel intermediates therefor |
| US4916217A (en) * | 1987-01-08 | 1990-04-10 | Bristol-Myers Company | Phosphorus containing derivatives of epipodophyllotoxin |
| JPS63192793A (ja) * | 1987-02-06 | 1988-08-10 | Nippon Kayaku Co Ltd | ４′−デメチル−エピポドフイロトキシン誘導体の新規エステル |
| US4874851A (en) * | 1987-07-01 | 1989-10-17 | Bristol-Meyers Company | 3',4'-dinitrogen substituted epipodophyllotoxin glucoside derivatives |
-
1988
- 1988-05-27 US US07/199,731 patent/US4904768A/en not_active Ceased
- 1988-07-21 MY MYPI88000819A patent/MY104321A/en unknown
- 1988-07-22 LU LU87290A patent/LU87290A1/fr active Protection Beyond IP Right Term
- 1988-07-25 YU YU01436/88A patent/YU143688A/xx unknown
- 1988-07-26 NO NO883299A patent/NO170284C/no not_active IP Right Cessation
- 1988-07-28 IT IT8821535A patent/IT1226825B/it active
- 1988-07-29 FR FR8810258A patent/FR2622193B1/fr not_active Expired - Lifetime
- 1988-07-29 NZ NZ225615A patent/NZ225615A/en unknown
- 1988-08-01 FI FI883596A patent/FI87790C/fi not_active IP Right Cessation
- 1988-08-01 IL IL87290A patent/IL87290A/xx not_active IP Right Cessation
- 1988-08-02 CZ CS19885412A patent/CZ286893B6/cs not_active IP Right Cessation
- 1988-08-02 SK SK5412-88A patent/SK541288A3/sk unknown
- 1988-08-03 NL NL8801934A patent/NL192683C/nl not_active IP Right Cessation
- 1988-08-03 SE SE8802815A patent/SE502214C2/sv not_active IP Right Cessation
- 1988-08-03 JP JP63194307A patent/JPH0699465B2/ja not_active Expired - Lifetime
- 1988-08-03 IE IE237888A patent/IE61040B1/en not_active IP Right Cessation
- 1988-08-03 PT PT88186A patent/PT88186B/pt not_active IP Right Cessation
- 1988-08-03 GB GB8818462A patent/GB2207674B/en not_active Expired - Lifetime
- 1988-08-03 ES ES8802434A patent/ES2010775A6/es not_active Expired
- 1988-08-03 HU HU905862A patent/HU208147B/hu unknown
- 1988-08-03 AT AT0195588A patent/AT398974B/de active
- 1988-08-03 HU HU884081A patent/HU202547B/hu unknown
- 1988-08-03 DD DD88326917A patent/DD299067A5/de unknown
- 1988-08-03 BE BE8800898A patent/BE1002982A4/fr not_active IP Right Cessation
- 1988-08-03 DD DD88318652A patent/DD274423A5/de unknown
- 1988-08-03 KR KR1019880009910A patent/KR900006230B1/ko not_active Expired
- 1988-08-03 DK DK434088A patent/DK169344B1/da not_active IP Right Cessation
- 1988-08-04 CH CH2962/88A patent/CH676716A5/de not_active IP Right Cessation
- 1988-08-04 GR GR880100512A patent/GR1000490B/el not_active IP Right Cessation
- 1988-08-04 DE DE3826562A patent/DE3826562A1/de active Granted
- 1988-08-04 CA CA000573861A patent/CA1310637C/en not_active Expired - Lifetime
-
1989
- 1989-12-14 US US07/450,718 patent/US5041424A/en not_active Expired - Lifetime
-
1990
- 1990-01-19 YU YU00103/90A patent/YU10390A/xx unknown
- 1990-01-19 YU YU00104/90A patent/YU10490A/xx unknown
-
1991
- 1991-10-30 CN CN91108384A patent/CN1027169C/zh not_active Expired - Lifetime
- 1991-11-29 SG SG1012/91A patent/SG101291G/en unknown
-
1992
- 1992-01-16 HK HK63/92A patent/HK6392A/xx not_active IP Right Cessation
- 1992-01-22 NO NO920277A patent/NO920277D0/no unknown
- 1992-01-31 DK DK92119A patent/DK11992D0/da not_active Application Discontinuation
- 1992-02-20 NO NO920665A patent/NO172440C/no not_active IP Right Cessation
- 1992-06-12 MX MX9202851A patent/MX173843B/es unknown
- 1992-07-10 CY CY1625A patent/CY1625A/en unknown
-
1994
- 1994-04-19 US US08/229,659 patent/USRE35524E/en not_active Expired - Lifetime
-
1995
- 1995-06-22 HU HU95P/P00387P patent/HU211960A9/hu unknown
-
1997
- 1997-09-24 LU LU90138C patent/LU90138I2/fr unknown
- 1997-12-05 NL NL970042C patent/NL970042I1/nl unknown
-
1998
- 1998-01-14 NO NO1998002C patent/NO1998002I1/no unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1027169C (zh) | 表鬼臼毒葡糖苷4′-磷酸酯衍生物的制备方法 | |
| CN1020194C (zh) | 二氟核苷衍生物的制备方法 | |
| KR101840893B1 (ko) | Ｎ―아실술폰아미드아포프토시스 촉진제 | |
| HK1047939B (zh) | 位阻醇或酚的水溶性前藥 | |
| CN1285843A (zh) | 化合物 | |
| CN1084177A (zh) | 具抗病毒和抗癌活性的2′-脱氧-2′，2′-二氟(4-取代嘧啶)核苷以及中间体 | |
| CN1346360A (zh) | 作为抗病毒剂的(1r,顺式)－4－(6－氨基－9h－嘌呤－9－基)－2－环戊烯－1－甲醇的氨基磷酸酯及一二和三磷酸酯 | |
| CN1013198B (zh) | 抗肿瘤的磺酰脲衍生物的制备方法 | |
| JP7573591B2 (ja) | Ｍｃｌ－１阻害剤としての大環状スピロ環誘導体 | |
| CN1023804C (zh) | 新型炔属、氰基芒霉素/腺苷衍生物的制备方法 | |
| KR20230035621A (ko) | Mcl-1의 억제제로서 인돌 유도체를 함유하는 마크로사이클릭 에테르 | |
| CN1047866A (zh) | N-杂芳基-嘌呤-6-胺的制备方法及其药用 | |
| CN1044911C (zh) | 制备前体药的方法 | |
| CN1278809A (zh) | 取代的苯并二氢吡喃衍生物 | |
| CN1033632A (zh) | 新颖的隐陡头霉素/腺苷衍生物 | |
| CN1020615C (zh) | 表鬼臼毒葡糖苷4′-磷酸酯衍生物的制备方法 | |
| AU2024280172A1 (en) | Novel double-stranded sirna, conjugate thereof, and use thereof | |
| EP4061819A1 (en) | Macrocyclic indole derivatives as mcl-1 inhibitors | |
| CN1261372A (zh) | 天然抗肿瘤性或抗病毒性物质及其用途 | |
| CN1332745A (zh) | 治疗癌症的新化合物 | |
| TW202227437A (zh) | 作為蛋白激酶抑制劑的取代的吡咯並[2, 3-b]吡啶及吡唑並[3,4-b]吡啶衍生物 | |
| CN1463975A (zh) | 新的三尖杉碱类的酯碱衍生物及其制法和其药物组合物与用途 | |
| CN88100826A (zh) | 核苷酸类似物的生产及其使用 | |
| CN1071929A (zh) | 表鬼臼脂素糖苷的磷酸和磺酸酯的制备方法 | |
| CN87100055A (zh) | 口服有效的膦酰羟酰脯氨酸及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CX01 | Expiry of patent term |