NL8002577A - Bis(4-demethoxydaunorubicine)dihydrazonderivaten en hun zouten. - Google Patents

Bis(4-demethoxydaunorubicine)dihydrazonderivaten en hun zouten. Download PDF

Info

Publication number: NL8002577A
Authority: NL; Netherlands
Prior art keywords: parts; formula; amino; diyl; bis
Prior art date: 1979-05-03

Application number

NL8002577A

Other languages

English (en)

Dutch (nl)

Original Assignee

Apple Martin Allen

Priority date (The priority date 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 date listed.)

1979-05-03

Filing date

1980-05-02

Publication date

1980-11-05

1980-05-02 Application filed by Apple Martin Allen filed Critical Apple Martin Allen

1980-11-05 Publication of NL8002577A publication Critical patent/NL8002577A/nl

Links

229960000908 idarubicin Drugs 0.000 title claims description 17
150000003839 salts Chemical class 0.000 title claims description 16
XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 title description 2
XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
239000001257 hydrogen Substances 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
125000002947 alkylene group Chemical group 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims 1
239000013543 active substance Substances 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
239000000243 solution Substances 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
235000002639 sodium chloride Nutrition 0.000 description 11
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
239000000047 product Substances 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
-1 amino dicarboxylic acid Chemical compound 0.000 description 9
239000000203 mixture Substances 0.000 description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
229910052786 argon Inorganic materials 0.000 description 8
239000002904 solvent Substances 0.000 description 8
150000005690 diesters Chemical class 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
208000032839 leukemia Diseases 0.000 description 6
238000000034 method Methods 0.000 description 6
0 BC[C@@]([*+](B)C1*(*)C(*)OC(*)C1)O Chemical compound BC[C@@]([*+](B)C1*(*)C(*)OC(*)C1)O 0.000 description 5
206010028980 Neoplasm Diseases 0.000 description 5
235000019441 ethanol Nutrition 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
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 4
229960000975 daunorubicin Drugs 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
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 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
239000002246 antineoplastic agent Substances 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
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 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000000118 anti-neoplastic effect Effects 0.000 description 2
230000002155 anti-virotic effect Effects 0.000 description 2
AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000001569 carbon dioxide Substances 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
PXJFLUYRGQUUIN-UHFFFAOYSA-N dimethyl 3-aminopentanedioate Chemical compound COC(=O)CC(N)CC(=O)OC PXJFLUYRGQUUIN-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000012458 free base Substances 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
238000002513 implantation Methods 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
230000001613 neoplastic effect Effects 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
229910000105 potassium hydride Inorganic materials 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
235000012239 silicon dioxide Nutrition 0.000 description 2
ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
210000004881 tumor cell Anatomy 0.000 description 2
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical class CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
101150065749 Churc1 gene Proteins 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 description 1
229930182847 D-glutamic acid Natural products 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Chemical class 0.000 description 1
SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
229920000084 Gum arabic Chemical class 0.000 description 1
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 description 1
102100034343 Integrase Human genes 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
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 1
241000252067 Megalops atlanticus Species 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical class [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
102100038239 Protein Churchill Human genes 0.000 description 1
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
241000700605 Viruses Species 0.000 description 1
210000000683 abdominal cavity Anatomy 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000000205 acacia gum Chemical class 0.000 description 1
229940009456 adriamycin Drugs 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000005215 alkyl ethers Chemical class 0.000 description 1
125000005263 alkylenediamine group Chemical group 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
229940034982 antineoplastic agent Drugs 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229940072107 ascorbate Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940050390 benzoate Drugs 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
238000007664 blowing Methods 0.000 description 1
239000001273 butane Substances 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
229940114081 cinnamate Drugs 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
238000010411 cooking Methods 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
WPJRFCZKZXBUNI-HCWXCVPCSA-N daunosamine Chemical class C[C@H](O)[C@@H](O)[C@@H](N)CC=O WPJRFCZKZXBUNI-HCWXCVPCSA-N 0.000 description 1
150000004985 diamines Chemical class 0.000 description 1
GTYMEGZAWBDMCY-UHFFFAOYSA-N dimethyl 3,5,7-triaminononanedioate;trihydrochloride Chemical compound Cl.Cl.Cl.COC(=O)CC(N)CC(N)CC(N)CC(=O)OC GTYMEGZAWBDMCY-UHFFFAOYSA-N 0.000 description 1
IGFCVYPDEKKJOV-UHFFFAOYSA-N dimethyl 3,7-diacetamido-5-hydroxynonanedioate Chemical compound COC(=O)CC(NC(C)=O)CC(O)CC(NC(C)=O)CC(=O)OC IGFCVYPDEKKJOV-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000008273 gelatin Chemical class 0.000 description 1
229920000159 gelatin Chemical class 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
QCNWZROVPSVEJA-UHFFFAOYSA-N heptadecanedioic acid Natural products OC(=O)CCCCCCCCCCCCCCCC(O)=O QCNWZROVPSVEJA-UHFFFAOYSA-N 0.000 description 1
229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
239000000395 magnesium oxide Substances 0.000 description 1
CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
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
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
KGCNHWXDPDPSBV-UHFFFAOYSA-N p-nitrobenzyl chloride Chemical compound [O-][N+](=O)C1=CC=C(CCl)C=C1 KGCNHWXDPDPSBV-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
229920000036 polyvinylpyrrolidone Chemical class 0.000 description 1
239000001267 polyvinylpyrrolidone Chemical class 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
239000000843 powder Substances 0.000 description 1
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
238000010839 reverse transcription Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000000661 sodium alginate Chemical class 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
JBJWASZNUJCEKT-UHFFFAOYSA-M sodium;hydroxide;hydrate Chemical compound O.[OH-].[Na+] JBJWASZNUJCEKT-UHFFFAOYSA-M 0.000 description 1
239000012453 solvate Substances 0.000 description 1
229940063673 spermidine Drugs 0.000 description 1
229940063675 spermine Drugs 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000001256 tonic effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
238000005406 washing Methods 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)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

NL8002577A 1979-05-03 1980-05-02 Bis(4-demethoxydaunorubicine)dihydrazonderivaten en hun zouten. NL8002577A (nl)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US06/035,657 US4275192A (en)	1979-05-03	1979-05-03	Bis(4-demethoxydaunorubicin)dihydrazone derivatives and pharmacologically acceptable salts thereof
US3565779		1979-05-03

Publications (1)

Publication Number	Publication Date
NL8002577A true NL8002577A (nl)	1980-11-05

Family

ID=21884000

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NL8002577A NL8002577A (nl)	1979-05-03	1980-05-02	Bis(4-demethoxydaunorubicine)dihydrazonderivaten en hun zouten.

Country Status (15)

Country	Link
US (1)	US4275192A (de)
JP (1)	JPS568398A (de)
AU (1)	AU532925B2 (de)
BE (1)	BE883106A (de)
CA (1)	CA1137471A (de)
CH (1)	CH643862A5 (de)
DE (1)	DE3016974A1 (de)
DK (1)	DK194280A (de)
ES (2)	ES8104320A1 (de)
FR (1)	FR2455595A1 (de)
GB (1)	GB2050364B (de)
IE (1)	IE49782B1 (de)
IT (1)	IT1143092B (de)
NL (1)	NL8002577A (de)
SE (1)	SE8003317L (de)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5162512A (en) *	1982-03-09	1992-11-10	Cytogen Corporation	Amine derivatives of anthracycline antibodies
US4950738A (en) *	1984-09-13	1990-08-21	Cytogen Corporation	Amine derivatives of anthracycline antibiotics
CA1248944A (en) *	1982-09-28	1989-01-17	Gareth J. Thomas	Anthracycline glycosides
FR2551442B1 (fr) *	1983-09-05	1987-04-30	Centre Nat Rech Scient	Nouveaux derives furaniques, leur preparation et leur application
JPS61227590A (ja) *	1985-04-02	1986-10-09	Microbial Chem Res Found	新規４′−デメチル−４−エピポドフイロトキシン誘導体
GB2196626B (en) *	1986-10-15	1990-09-19	Erba Farmitalia	Antitumor anthracycline glycosides, their preparation, intermediates thereof, and compositions and use therefor
IL106992A (en) *	1988-02-11	1994-06-24	Bristol Myers Squibb Co	Acylhydrazone derivatives of anthracycline and methods for their preparation

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3957755A (en) *	1967-10-18	1976-05-18	Rhone-Poulenc S.A.	Naphthacene derivatives
US4112217A (en) *	1977-09-02	1978-09-05	Sri International	Bis-hydrazones of daunomycin and adriamycin
US4125704A (en) *	1977-09-14	1978-11-14	Sri International	Phenyl-substituted rubidazone analogs

1979
- 1979-05-03 US US06/035,657 patent/US4275192A/en not_active Expired - Lifetime
1980
- 1980-04-30 FR FR8009856A patent/FR2455595A1/fr active Granted
- 1980-05-01 DK DK194280A patent/DK194280A/da not_active Application Discontinuation
- 1980-05-02 DE DE19803016974 patent/DE3016974A1/de not_active Withdrawn
- 1980-05-02 SE SE8003317A patent/SE8003317L/xx not_active Application Discontinuation
- 1980-05-02 ES ES491116A patent/ES8104320A1/es not_active Expired
- 1980-05-02 GB GB8014862A patent/GB2050364B/en not_active Expired
- 1980-05-02 AU AU58039/80A patent/AU532925B2/en not_active Ceased
- 1980-05-02 NL NL8002577A patent/NL8002577A/nl unknown
- 1980-05-02 CA CA000351196A patent/CA1137471A/en not_active Expired
- 1980-05-05 CH CH346980A patent/CH643862A5/de not_active IP Right Cessation
- 1980-05-05 BE BE2/462A patent/BE883106A/fr not_active IP Right Cessation
- 1980-05-05 IE IE912/80A patent/IE49782B1/en unknown
- 1980-05-05 IT IT48583/80A patent/IT1143092B/it active
- 1980-05-06 JP JP5985280A patent/JPS568398A/ja active Pending
- 1980-12-16 ES ES497801A patent/ES497801A0/es active Granted

Also Published As

Publication number	Publication date
CH643862A5 (de)	1984-06-29
JPS568398A (en)	1981-01-28
IT1143092B (it)	1986-10-22
GB2050364B (en)	1983-04-27
ES491116A0 (es)	1981-04-16
ES8104320A1 (es)	1981-04-16
BE883106A (fr)	1980-11-05
SE8003317L (sv)	1980-11-04
FR2455595A1 (fr)	1980-11-28
FR2455595B1 (de)	1983-08-12
AU532925B2 (en)	1983-10-20
ES8200899A1 (es)	1981-11-16
DK194280A (da)	1980-11-04
AU5803980A (en)	1980-11-06
IE800912L (en)	1980-11-03
IT8048583A0 (it)	1980-05-05
IE49782B1 (en)	1985-12-11
US4275192A (en)	1981-06-23
GB2050364A (en)	1981-01-07
CA1137471A (en)	1982-12-14
DE3016974A1 (de)	1980-11-13
ES497801A0 (es)	1981-11-16

Publication	Publication Date	Title
FI73682B (fi)	1987-07-31	Foerfarande foer framstaellning av antiviralt 9-(1,3-dihydroxi-2-propoximetyl)guanin samt mellanprodukt.
Deutsch et al.	1989	Synthesis of congeners and prodrugs. 3. Water-soluble prodrugs of taxol with potent antitumor activity
CS265248B2 (en)	1989-10-13	Process for preparing analogs of rebeccamycine
NL8002577A (nl)	1980-11-05	Bis(4-demethoxydaunorubicine)dihydrazonderivaten en hun zouten.
US5298495A (en)	1994-03-29	Partricin derivatives
CN114736214B (zh)	2024-04-09	一种倍半萜衍生物、其药物组合物及其制备方法和用途
GB2073752A (en)	1981-10-21	2,6-diaminobularines
EP0273401B1 (de)	1992-11-11	Isoindolin-1-on-Derivat und antiarrhythmisches Mittel
CN106565763A (zh)	2017-04-19	pH敏感的轴向取代硅酞菁配合物及其制备方法和在医药上的应用
JP3848158B2 (ja)	2006-11-22	新規のキサントン化合物、その製造および医薬としての使用
HU217551B (hu)	2000-02-28	6[(2-Hidroxi-etil)-amino-alkil]-5,11-dioxo-5,6-dihidro-11H-indén[1,2-c]izokinolin-származékok, valamint eljárás előállításukra, továbbá hatóanyagként e vegyületeket tartalmazó gyógyászati készítmények
CN101365461A (zh)	2009-02-11	舒林酸（sulindac）衍生物、其用途和其制备
US7019132B2 (en)	2006-03-28	Porphyrin derivatives
WO1999031084A1 (en)	1999-06-24	Brefeldin a derivatives
Agrawal et al.	1968	Potential Antitumor Agents III: Sodium Salts of α-[N]-Heterocyclic Carboxaldehyde Thiosemicarbazones
US10947248B2 (en)	2021-03-16	4β-amidotriazole linked podophyllotoxin derivatives as potential anticancer agents
CN113773356B (zh)	2024-02-02	一种胡黄连苷ii衍生物及其制备方法和应用
KR101068259B1 (ko)	2011-09-28	헤테로사이클기에 고리－축합된 신규 베툴린산 유도체
CN110615766B (zh)	2021-04-20	双取代的α、β不饱和酮及其制备方法和应用
JPH06211762A (ja)	1994-08-02	Ｎ−メチルデアセチルコルヒセインアミド誘導体
CN113999211A (zh)	2022-02-01	一类特异性抗前列腺癌活性的含1,2,3-三氮唑的吲唑骨架衍生物
JP2018536643A (ja)	2018-12-13	一置換又は多置換の油水両親媒性ヒポクレリン誘導体及びその製造方法と使用
JPH06199749A (ja)	1994-07-19	Ｎ−メチルデアセチルコルヒセインアミド誘導体
PL188075B1 (pl)	2004-12-31	Rozpuszczalne w wodzie C-pierścieniowe analogi 20(S)-kamptotecyny, kompozycja farmaceutyczna zawierająca te związki, ich zastosowanie oraz sposób wytwarzania
JPH0417195B2 (de)	1992-03-25