ES2695162T3 - Nuevos derivados de morfolinil antraciclina - Google Patents
Nuevos derivados de morfolinil antraciclina Download PDFInfo
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- ES2695162T3 ES2695162T3 ES14719005T ES14719005T ES2695162T3 ES 2695162 T3 ES2695162 T3 ES 2695162T3 ES 14719005 T ES14719005 T ES 14719005T ES 14719005 T ES14719005 T ES 14719005T ES 2695162 T3 ES2695162 T3 ES 2695162T3
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- alkyl
- amino
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- 229940045799 anthracyclines and related substance Drugs 0.000 title description 17
- 125000002757 morpholinyl group Chemical group 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 233
- 239000001257 hydrogen Substances 0.000 claims abstract description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 11
- 101100134929 Gallus gallus COR9 gene Proteins 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 85
- 238000000034 method Methods 0.000 claims description 55
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 206010028980 Neoplasm Diseases 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 210000004027 cell Anatomy 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 11
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 8
- 239000002246 antineoplastic agent Substances 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- 229940127089 cytotoxic agent Drugs 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- FFHWGQQFANVOHV-UHFFFAOYSA-N dimethyldioxirane Chemical compound CC1(C)OO1 FFHWGQQFANVOHV-UHFFFAOYSA-N 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 4
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical class [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 4
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 claims description 4
- 201000005787 hematologic cancer Diseases 0.000 claims description 4
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
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- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
- 206010003571 Astrocytoma Diseases 0.000 claims description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 2
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 2
- 206010016935 Follicular thyroid cancer Diseases 0.000 claims description 2
- 208000032612 Glial tumor Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
- 206010027406 Mesothelioma Diseases 0.000 claims description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 2
- 201000010208 Seminoma Diseases 0.000 claims description 2
- 206010042971 T-cell lymphoma Diseases 0.000 claims description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
- 201000006083 Xeroderma Pigmentosum Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 210000003679 cervix uteri Anatomy 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 210000003238 esophagus Anatomy 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 230000001926 lymphatic effect Effects 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 208000007538 neurilemmoma Diseases 0.000 claims description 2
- 201000008968 osteosarcoma Diseases 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 2
- 206010039667 schwannoma Diseases 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 208000001608 teratocarcinoma Diseases 0.000 claims description 2
- 210000001685 thyroid gland Anatomy 0.000 claims description 2
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 claims description 2
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 claims 1
- 208000003950 B-cell lymphoma Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- -1 hormonal agents Substances 0.000 description 42
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 33
- 239000000243 solution Substances 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 22
- 239000007858 starting material Substances 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 14
- 238000010992 reflux Methods 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000003960 organic solvent Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 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 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 7
- 229910052736 halogen Inorganic materials 0.000 description 7
- 150000002367 halogens Chemical class 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- XGIHYVDWXQWVAA-RQZFFVEVSA-N (7S,9S)-4-[(3,4-dimethoxyphenyl)methylamino]-6,7,9,11-tetrahydroxy-9-(2-methyl-1,3-dioxolan-2-yl)-8,10-dihydro-7H-tetracene-5,12-dione Chemical compound COc1ccc(CNc2cccc3C(=O)c4c(O)c5C[C@](O)(C[C@H](O)c5c(O)c4C(=O)c23)C2(C)OCCO2)cc1OC XGIHYVDWXQWVAA-RQZFFVEVSA-N 0.000 description 5
- 0 CC1OCCN(C2C3)C1OC2[C@@](C)OC3OC(CC(*)(C1)O)c(c(O)c2C(c3c4cccc3*)=O)c1c(O)c2C4=O Chemical compound CC1OCCN(C2C3)C1OC2[C@@](C)OC3OC(CC(*)(C1)O)c(c(O)c2C(c3c4cccc3*)=O)c1c(O)c2C4=O 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
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- 229960004679 doxorubicin Drugs 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
- 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 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 3
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- LXGSBKPHFALKIT-YBTHPKLGSA-N (7S,9S)-9-acetyl-4-amino-6,7,9,11-tetrahydroxy-8,10-dihydro-7H-tetracene-5,12-dione Chemical compound CC(=O)[C@@]1(O)C[C@H](O)c2c(O)c3C(=O)c4c(N)cccc4C(=O)c3c(O)c2C1 LXGSBKPHFALKIT-YBTHPKLGSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 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
- KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical compound NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 description 2
- BTJIUGUIPKRLHP-UHFFFAOYSA-M 4-nitrophenolate Chemical compound [O-]C1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-M 0.000 description 2
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- XXFXTBNFFMQVKJ-UHFFFAOYSA-N [diphenyl(trityloxy)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXFXTBNFFMQVKJ-UHFFFAOYSA-N 0.000 description 2
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- 230000003115 biocidal effect Effects 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
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- 238000012054 celltiter-glo Methods 0.000 description 2
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- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 2
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 2
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- DQRLCTAGMVGVFH-UHFFFAOYSA-N cyanide;hydrochloride Chemical compound Cl.N#[C-] DQRLCTAGMVGVFH-UHFFFAOYSA-N 0.000 description 2
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- 239000000824 cytostatic agent Substances 0.000 description 2
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- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C07H9/00—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
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- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
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Landscapes
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- Communicable Diseases (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13165707 | 2013-04-29 | ||
| PCT/EP2014/058262 WO2014177441A1 (en) | 2013-04-29 | 2014-04-23 | New morpholinyl anthracycline derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2695162T3 true ES2695162T3 (es) | 2019-01-02 |
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| ES14719005T Active ES2695162T3 (es) | 2013-04-29 | 2014-04-23 | Nuevos derivados de morfolinil antraciclina |
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| US (1) | US9828405B2 (enExample) |
| EP (1) | EP2991993B1 (enExample) |
| JP (1) | JP2016517871A (enExample) |
| CN (1) | CN105164138B (enExample) |
| DK (1) | DK2991993T3 (enExample) |
| ES (1) | ES2695162T3 (enExample) |
| RU (1) | RU2666356C2 (enExample) |
| WO (1) | WO2014177441A1 (enExample) |
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| RU2715902C2 (ru) * | 2014-11-05 | 2020-03-04 | НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. | Функционализированные производные морфолинилантрациклина |
| CN108864221B (zh) * | 2018-06-08 | 2022-04-01 | 中国科学院上海有机化学研究所 | 阿克拉霉素类似物及其制法和用途 |
| CN110776501B (zh) * | 2019-08-22 | 2021-04-02 | 联宁（苏州）生物制药有限公司 | 一种用于抗体药物偶联物的药物毒素pnu-159682的制备方法及其中间体 |
| CN115043895A (zh) * | 2022-07-15 | 2022-09-13 | 戊言医药科技（上海）有限公司 | 一种pnu-159682及其中间体的制备方法 |
| CN115651043A (zh) * | 2022-10-27 | 2023-01-31 | 戊言医药科技（上海）有限公司 | 一种蒽环类毒素衍生物的制备方法 |
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| US3803124A (en) | 1968-04-12 | 1974-04-09 | Farmaceutici It Soc | Process for the preparation of adriamycin and adriamycinone and adriamycin derivatives |
| GB1511680A (en) * | 1975-11-18 | 1978-05-24 | Farmaceutici Italia | Daunosaminyl anthracyclinones |
| US4133877A (en) | 1976-07-08 | 1979-01-09 | Societa Farmaceutici Italia S.P.A. | Anthracycline ethers and use therefor |
| NZ224252A (en) * | 1987-04-21 | 1991-09-25 | Erba Carlo Spa | An anthracycline glycoside and its preparation |
| GB8804429D0 (en) | 1988-02-25 | 1988-03-23 | Erba Carlo Spa | New 4-demethyl-4-0-(fluorobenzensulfonyl)anthracycline glycosides |
| GB2225781A (en) | 1988-05-13 | 1990-06-13 | Erba Carlo Spa | 10-Noranthracyclines |
| GB8902709D0 (en) | 1989-02-07 | 1989-03-30 | Erba Carlo Spa | New 4'-epi-4'-amino anthracyclines |
| GB8905668D0 (en) * | 1989-03-13 | 1989-04-26 | Erba Carlo Spa | New 3'-(4-morpholinyl)-and 3'-(2-methoxy-4-morpholinyl)-anthracycline derivatives |
| RU2081878C1 (ru) * | 1989-03-13 | 1997-06-20 | Фармиталиа Карло Эрба С.Р.Л. | Антрациклин гликозид и способ его получения |
| EP0434960B1 (en) | 1989-12-19 | 1996-09-18 | PHARMACIA S.p.A. | Chiral 1,5-diiodo-2-methoxy or benzyloxy intermediates |
| GB9019933D0 (en) * | 1990-09-12 | 1990-10-24 | Erba Carlo Spa | 13-dihydro-3'-(2-alkoxy-4-morphlinyl)anthracyclines |
| GB2296495B (en) | 1994-12-23 | 1998-04-15 | Erba Carlo Spa | Anthracycline derivatives |
| GB2315067B (en) * | 1996-07-11 | 2000-02-16 | Pharmacia Spa | Morpholinyl anthracycline derivatives |
| FR2856687B1 (fr) * | 2003-06-25 | 2005-09-16 | Servier Lab | Nouveaux derives de benzo[a]pyrano[3,2-h]acridin-7-one, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| AU2009270988A1 (en) * | 2008-07-15 | 2010-01-21 | Genentech, Inc. | Anthracycline derivative conjugates, process for their preparation and their use as antitumor compounds |
| EP2646456B1 (en) * | 2010-12-02 | 2015-01-21 | Nerviano Medical Sciences S.r.l. | Process for the preparation of morpholinyl anthracycline derivatives |
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- 2014-04-23 WO PCT/EP2014/058262 patent/WO2014177441A1/en not_active Ceased
- 2014-04-23 JP JP2016511009A patent/JP2016517871A/ja active Pending
- 2014-04-23 US US14/787,667 patent/US9828405B2/en active Active
- 2014-04-23 RU RU2015150994A patent/RU2666356C2/ru active
- 2014-04-23 DK DK14719005.2T patent/DK2991993T3/en active
- 2014-04-23 ES ES14719005T patent/ES2695162T3/es active Active
- 2014-04-23 EP EP14719005.2A patent/EP2991993B1/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US9828405B2 (en) | 2017-11-28 |
| CN105164138A (zh) | 2015-12-16 |
| HK1218646A1 (zh) | 2017-03-03 |
| EP2991993B1 (en) | 2018-06-06 |
| RU2015150994A (ru) | 2017-06-06 |
| DK2991993T3 (en) | 2018-07-30 |
| CN105164138B (zh) | 2017-11-07 |
| RU2666356C2 (ru) | 2018-09-07 |
| JP2016517871A (ja) | 2016-06-20 |
| WO2014177441A1 (en) | 2014-11-06 |
| US20160075730A1 (en) | 2016-03-17 |
| EP2991993A1 (en) | 2016-03-09 |
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