SK281797B6 - Antracyklínové disacharidy, spôsob ich prípravy a farmaceutické prípravky s ich obsahom - Google Patents
Antracyklínové disacharidy, spôsob ich prípravy a farmaceutické prípravky s ich obsahom Download PDFInfo
- Publication number
- SK281797B6 SK281797B6 SK396-96A SK39696A SK281797B6 SK 281797 B6 SK281797 B6 SK 281797B6 SK 39696 A SK39696 A SK 39696A SK 281797 B6 SK281797 B6 SK 281797B6
- Authority
- SK
- Slovakia
- Prior art keywords
- hexopyranosyl
- formula
- dideoxy
- amino
- group
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 24
- 230000008569 process Effects 0.000 title claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 229940045799 anthracyclines and related substance Drugs 0.000 title claims description 7
- 150000002016 disaccharides Chemical class 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 230000001093 anti-cancer Effects 0.000 claims abstract description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- -1 dimethyl tert-butylsilyl Chemical group 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- YOFDHOWPGULAQF-UHFFFAOYSA-N Daunomycin-Aglycone Natural products C1C(O)(C(C)=O)CC(O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-UHFFFAOYSA-N 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- YOFDHOWPGULAQF-MQJDWESPSA-N (7s,9s)-9-acetyl-6,7,9,11-tetrahydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound C1[C@@](O)(C(C)=O)C[C@H](O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-MQJDWESPSA-N 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- IBZGBXXTIGCACK-CWKPULSASA-N Adriamycinone Chemical compound C1[C@@](O)(C(=O)CO)C[C@H](O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O IBZGBXXTIGCACK-CWKPULSASA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000009833 condensation Methods 0.000 claims description 6
- 230000005494 condensation Effects 0.000 claims description 6
- 238000010511 deprotection reaction Methods 0.000 claims description 6
- OTLNPYWUJOZPPA-UHFFFAOYSA-M 4-nitrobenzoate Chemical compound [O-]C(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-M 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 230000031709 bromination Effects 0.000 claims description 3
- 238000005893 bromination reaction Methods 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims description 3
- RBWNDBNSJFCLBZ-UHFFFAOYSA-N 7-methyl-5,6,7,8-tetrahydro-3h-[1]benzothiolo[2,3-d]pyrimidine-4-thione Chemical compound N1=CNC(=S)C2=C1SC1=C2CCC(C)C1 RBWNDBNSJFCLBZ-UHFFFAOYSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000004280 Sodium formate Substances 0.000 claims description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- 125000003158 alcohol group Chemical group 0.000 claims description 2
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 claims description 2
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 claims description 2
- 229910052796 boron Inorganic materials 0.000 claims description 2
- 229920001429 chelating resin Polymers 0.000 claims description 2
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 150000003840 hydrochlorides Chemical class 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 239000003456 ion exchange resin Substances 0.000 claims description 2
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 2
- 229910000474 mercury oxide Inorganic materials 0.000 claims description 2
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 claims description 2
- 239000002808 molecular sieve Substances 0.000 claims description 2
- 229910052759 nickel Inorganic materials 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 2
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 claims description 2
- 235000019254 sodium formate Nutrition 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 2
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 claims description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 150000007524 organic acids Chemical class 0.000 claims 2
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 claims 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000002940 palladium Chemical class 0.000 claims 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims 1
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 56
- 206010028980 Neoplasm Diseases 0.000 description 34
- 229960004679 doxorubicin Drugs 0.000 description 28
- 241000699670 Mus sp. Species 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 230000000259 anti-tumor effect Effects 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 206010041067 Small cell lung cancer Diseases 0.000 description 6
- 230000034994 death Effects 0.000 description 6
- 231100000517 death Toxicity 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 208000000587 small cell lung carcinoma Diseases 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 150000001720 carbohydrates Chemical group 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 150000002338 glycosides Chemical group 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000010200 validation analysis Methods 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 238000005858 glycosidation reaction Methods 0.000 description 4
- 229930182470 glycoside Natural products 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 3
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 2
- 241000353790 Doru Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- GJFNRSDCSTVPCJ-UHFFFAOYSA-N 1,8-bis(dimethylamino)naphthalene Chemical compound C1=CC(N(C)C)=C2C(N(C)C)=CC=CC2=C1 GJFNRSDCSTVPCJ-UHFFFAOYSA-N 0.000 description 1
- IGHQOFUUDYGVMD-UHFFFAOYSA-N 1-methoxy-4-[[(4-methoxyphenyl)-diphenylmethoxy]-diphenylmethyl]benzene Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 IGHQOFUUDYGVMD-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101150097381 Mtor gene Proteins 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-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011717 athymic nude mouse Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229920005549 butyl rubber Polymers 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 239000008232 de-aerated water Substances 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 239000008215 water for injection Substances 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
- C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITFI930187A IT1262565B (it) | 1993-09-30 | 1993-09-30 | Disaccaridi di antracicline, loro processi di preparazione e composizioni farmaceutiche che li contengono. |
PCT/EP1994/003201 WO1995009173A1 (en) | 1993-09-30 | 1994-09-26 | Anthracycline disaccharides, process for their preparation, and pharmaceutical compositions containing them |
Publications (2)
Publication Number | Publication Date |
---|---|
SK39696A3 SK39696A3 (en) | 1996-11-06 |
SK281797B6 true SK281797B6 (sk) | 2001-08-06 |
Family
ID=11350615
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK396-96A SK281797B6 (sk) | 1993-09-30 | 1994-09-26 | Antracyklínové disacharidy, spôsob ich prípravy a farmaceutické prípravky s ich obsahom |
Country Status (27)
Country | Link |
---|---|
US (1) | US5801152A (ru) |
EP (1) | EP0721456B1 (ru) |
JP (1) | JP3836503B2 (ru) |
KR (1) | KR100341166B1 (ru) |
CN (1) | CN1042032C (ru) |
AT (1) | ATE178901T1 (ru) |
AU (1) | AU688374B2 (ru) |
BG (1) | BG62289B1 (ru) |
BR (2) | BR9407679A (ru) |
CZ (1) | CZ288462B6 (ru) |
DE (1) | DE69417907T2 (ru) |
DK (1) | DK0721456T3 (ru) |
ES (1) | ES2132429T3 (ru) |
FI (1) | FI113541B (ru) |
GE (1) | GEP20002095B (ru) |
GR (1) | GR3030731T3 (ru) |
HU (1) | HU227309B1 (ru) |
IT (1) | IT1262565B (ru) |
NO (1) | NO305400B1 (ru) |
NZ (1) | NZ273624A (ru) |
PL (1) | PL179399B1 (ru) |
RO (1) | RO115525B1 (ru) |
RU (1) | RU2144540C1 (ru) |
SK (1) | SK281797B6 (ru) |
TW (1) | TW404950B (ru) |
UA (1) | UA41951C2 (ru) |
WO (1) | WO1995009173A1 (ru) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1271689B (it) * | 1994-08-04 | 1997-06-04 | Menarini Farma Ind | 8-fluoro-antracicline, loro processi di preparazione e composizioni farmaceutiche che le contengono |
IT1307846B1 (it) | 1999-03-09 | 2001-11-19 | Menarini Ricerche Spa | L-arabino disaccaridi di antracicline, loro processi di preparazione ecomposizioni farmaceutiche che li contengono. |
CN112010913B (zh) * | 2019-05-31 | 2022-06-21 | 南京正大天晴制药有限公司 | 4-脱氧柔红霉素的制备方法 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1561507A (en) * | 1976-11-17 | 1980-02-20 | Farmaceutici Italia | Snthracycline disaccharides |
US4201773A (en) * | 1978-07-26 | 1980-05-06 | The United States Of America As Represented By The Department Of Health, Education And Welfare | 7-O-(2,6-Dideoxy-α-L-lyxo-hexopyranosyl)-daunomycinone, desmethoxy daunomycinone, adriamycinone, and carminomycinone |
DE3641833A1 (de) * | 1986-12-08 | 1988-06-09 | Behringwerke Ag | Zytostatisch wirksame anthracyclinderivate |
US4918172A (en) * | 1987-10-06 | 1990-04-17 | Sanraku Incorporated | Anthracycline antibiotics |
AU4752190A (en) * | 1988-12-28 | 1990-08-01 | Board Of Regents, The University Of Texas System | 3'-deamino analogs of esorubicin and methods for their use |
IT1241927B (it) * | 1990-05-14 | 1994-02-01 | Menarini Farma Ind | 3'-deamino-4'-deossi-4'-amino-8-fluoroantra- cicline processi per la loro preparazione e composizioni farmaceutiche che le contengono |
WO1992007862A1 (en) * | 1990-10-30 | 1992-05-14 | Yale University | Antibiotics improved by conjugation with stereospecific carbohydrtes and methods for carbohydrate stereoselectivity |
-
1993
- 1993-09-30 IT ITFI930187A patent/IT1262565B/it active IP Right Grant
-
1994
- 1994-09-26 UA UA96031231A patent/UA41951C2/ru unknown
- 1994-09-26 CZ CZ1996904A patent/CZ288462B6/cs not_active IP Right Cessation
- 1994-09-26 AT AT94927649T patent/ATE178901T1/de active
- 1994-09-26 CN CN94194276A patent/CN1042032C/zh not_active Expired - Lifetime
- 1994-09-26 SK SK396-96A patent/SK281797B6/sk not_active IP Right Cessation
- 1994-09-26 BR BR9407679A patent/BR9407679A/pt not_active Application Discontinuation
- 1994-09-26 KR KR1019960701668A patent/KR100341166B1/ko not_active IP Right Cessation
- 1994-09-26 RO RO96-00687A patent/RO115525B1/ro unknown
- 1994-09-26 RU RU96110287A patent/RU2144540C1/ru not_active IP Right Cessation
- 1994-09-26 AU AU76986/94A patent/AU688374B2/en not_active Ceased
- 1994-09-26 EP EP94927649A patent/EP0721456B1/en not_active Expired - Lifetime
- 1994-09-26 ES ES94927649T patent/ES2132429T3/es not_active Expired - Lifetime
- 1994-09-26 WO PCT/EP1994/003201 patent/WO1995009173A1/en active IP Right Grant
- 1994-09-26 DE DE69417907T patent/DE69417907T2/de not_active Expired - Lifetime
- 1994-09-26 JP JP51010695A patent/JP3836503B2/ja not_active Expired - Fee Related
- 1994-09-26 PL PL94313708A patent/PL179399B1/pl not_active IP Right Cessation
- 1994-09-26 GE GEAP19943110A patent/GEP20002095B/en unknown
- 1994-09-26 NZ NZ273624A patent/NZ273624A/en not_active IP Right Cessation
- 1994-09-26 HU HU9600812A patent/HU227309B1/hu not_active IP Right Cessation
- 1994-09-26 DK DK94927649T patent/DK0721456T3/da active
-
1995
- 1995-03-28 TW TW084103178A patent/TW404950B/zh not_active IP Right Cessation
-
1996
- 1996-03-15 NO NO961061A patent/NO305400B1/no not_active IP Right Cessation
- 1996-03-28 US US08/644,602 patent/US5801152A/en not_active Expired - Lifetime
- 1996-03-29 BG BG100466A patent/BG62289B1/bg not_active Expired - Lifetime
- 1996-03-29 FI FI961423A patent/FI113541B/fi not_active IP Right Cessation
-
1997
- 1997-05-13 BR BR1100550-5A patent/BR1100550A/pt active IP Right Grant
-
1999
- 1999-07-09 GR GR990401810T patent/GR3030731T3/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
BG60535B2 (bg) | Нови морфолинови производни на даунорубицина и на доксорубицина | |
EP2223929A1 (en) | Gambogic glycoside derivatives and analogs, the preparation and the application thereof | |
US20160256481A1 (en) | Use of water soluble platinum complex in preparing drugs for prevention and treatment of cancers | |
US20140349955A1 (en) | Use of fluorine-containing water soluble platinum complex in preparing drugs for prevention and treatment of cancers | |
PT89662B (pt) | Processo para a preparacao de novos glicosidos antraciclinicos e de composicoes farmaceuticas que os contem | |
EP0889898B1 (en) | Morpholinyl anthracycline derivatives | |
CA2231365A1 (en) | Bismuth salts of antibiotics of the moenomycin group, processes for their preparation, their use and pharmaceuticals comprising such salts | |
SK281797B6 (sk) | Antracyklínové disacharidy, spôsob ich prípravy a farmaceutické prípravky s ich obsahom | |
US7737123B2 (en) | Multidrug resistant anticancer anthracyclines | |
US7683163B2 (en) | Colchicoside analogues | |
US4302449A (en) | Carminomycin analogue | |
EP0128670A1 (en) | 4-Demethoxy-3'-deamino-3'(4-morpholinyl) derivatives of anthracycline anticancer antibiotics | |
AU7304096A (en) | Novel amine derivatives of epipodophyllotoxin 2", 3"-dideoxyglycosides, preparation method therefor and use thereof as a drug and for treating cancer | |
US6653289B1 (en) | L-arabino-disaccharides of anthracyclines, processes for their preparation, and pharmaceutical compositions containing them | |
CS235979B2 (en) | Method of new anti-tumor analogues-daunorubicine and doxorubicine production | |
ES2245734T3 (es) | Derivados antitumorales de acido 14-sulfonico de glucosido de antraciclina. | |
KR20210100560A (ko) | 화학적 합성에 의한 악사카신의 제조방법 | |
FI89496B (fi) | Foerfarande foer framstaellning av 4-demetoxi-4-aminoantracykliner | |
GB2287463A (en) | Bis-anthracycline derivatives | |
KR20010043400A (ko) | 신규 안트라사이클린 유도체 및 그 제조방법 | |
SK415191A3 (sk) | Antracyklínglykozidy, spôsob ich prípravy a farmaceutický prostriedok, ktorý ich obsahuje | |
HRP950092A2 (en) | Anthracycline disaccharides, process for their preparation, and pharmaceutical compositions containing them |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20130926 |