ES2942468T3 - Compuestos que contienen deuterio - Google Patents
Compuestos que contienen deuterio Download PDFInfo
- Publication number
- ES2942468T3 ES2942468T3 ES19790194T ES19790194T ES2942468T3 ES 2942468 T3 ES2942468 T3 ES 2942468T3 ES 19790194 T ES19790194 T ES 19790194T ES 19790194 T ES19790194 T ES 19790194T ES 2942468 T3 ES2942468 T3 ES 2942468T3
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- ES
- Spain
- Prior art keywords
- melflufen
- deuterium
- compound
- mol
- iii
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229910052805 deuterium Inorganic materials 0.000 title claims abstract description 145
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 title claims abstract description 142
- 150000001875 compounds Chemical class 0.000 title claims abstract description 80
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 10
- 238000011321 prophylaxis Methods 0.000 claims description 8
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 6
- 229940124597 therapeutic agent Drugs 0.000 claims description 6
- 208000034578 Multiple myelomas Diseases 0.000 claims description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229940124622 immune-modulator drug Drugs 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- YQZNKYXGZSVEHI-VXKWHMMOSA-N ethyl (2s)-2-[[(2s)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoate Chemical class C([C@@H](C(=O)OCC)NC(=O)[C@@H](N)CC=1C=CC(=CC=1)N(CCCl)CCCl)C1=CC=C(F)C=C1 YQZNKYXGZSVEHI-VXKWHMMOSA-N 0.000 description 114
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 48
- 229960001924 melphalan Drugs 0.000 description 48
- 238000001802 infusion Methods 0.000 description 45
- 241000282472 Canis lupus familiaris Species 0.000 description 25
- 239000002207 metabolite Substances 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 230000036470 plasma concentration Effects 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 15
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- 238000000034 method Methods 0.000 description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
- 125000004429 atom Chemical group 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
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- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 230000009885 systemic effect Effects 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- -1 amino acids Chemical class 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 231100000607 toxicokinetics Toxicity 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- LFQSCWFLJHTTHZ-LIDOUZCJSA-N ethanol-d6 Chemical compound [2H]OC([2H])([2H])C([2H])([2H])[2H] LFQSCWFLJHTTHZ-LIDOUZCJSA-N 0.000 description 5
- RNFBCJJCMLRNIG-JTQLQIEISA-N ethyl (2s)-2-amino-3-(4-fluorophenyl)propanoate Chemical compound CCOC(=O)[C@@H](N)CC1=CC=C(F)C=C1 RNFBCJJCMLRNIG-JTQLQIEISA-N 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000012453 solvate Substances 0.000 description 5
- 238000000825 ultraviolet detection Methods 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229940100198 alkylating agent Drugs 0.000 description 4
- 239000002168 alkylating agent Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- XWHHYOYVRVGJJY-QMMMGPOBSA-N 4-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-QMMMGPOBSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 108090000371 Esterases Proteins 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 229930006000 Sucrose Natural products 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- OAEMSIFAXHTNOJ-JRNXGPPGSA-N (2S)-2-[[(2S)-2-amino-3-[4-[bis(2-chloro-1,1,2,2-tetradeuterioethyl)amino]phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoic acid Chemical compound [2H]C([2H])(C([2H])([2H])Cl)N(C([2H])([2H])C([2H])([2H])Cl)C1=CC=C(C[C@@H](C(N[C@@H](CC(C=C2)=CC=C2F)C(O)=O)=O)N)C=C1 OAEMSIFAXHTNOJ-JRNXGPPGSA-N 0.000 description 2
- CHADEQDQBURGHL-UHFFFAOYSA-N (6'-acetyloxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl) acetate Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(OC(C)=O)C=C1OC1=CC(OC(=O)C)=CC=C21 CHADEQDQBURGHL-UHFFFAOYSA-N 0.000 description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 2
- 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 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-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
- 102000004190 Enzymes Human genes 0.000 description 2
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
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- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
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- 230000002152 alkylating effect Effects 0.000 description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
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- 125000004431 deuterium atom Chemical group 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
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- ZCMWSKHHXLCVHI-VROPFNGYSA-N ethyl (2S)-2-[[(2S)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoate hydrochloride Chemical class Cl.C([C@@H](C(=O)OCC)NC(=O)[C@@H](N)CC=1C=CC(=CC=1)N(CCCl)CCCl)C1=CC=C(F)C=C1 ZCMWSKHHXLCVHI-VROPFNGYSA-N 0.000 description 2
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
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- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
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- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108020005199 Dehydrogenases Proteins 0.000 description 1
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- 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
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Classifications
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- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
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| GBGB1909695.7A GB201909695D0 (en) | 2019-07-05 | 2019-07-05 | Compounds |
| PCT/EP2019/078250 WO2020079165A1 (en) | 2018-10-18 | 2019-10-17 | Compounds containing deuterium |
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| GB201905477D0 (en) * | 2019-04-17 | 2019-05-29 | Oncopeptides Ab | Novel formulations |
| EP4347615B1 (en) * | 2021-06-01 | 2025-05-21 | Synthon B.V. | Process for making melflufen or a salt thereof |
| GB202109895D0 (en) | 2021-07-08 | 2021-08-25 | Oncopeptides Ab | Novel treatments |
| GB202109896D0 (en) | 2021-07-08 | 2021-08-25 | Oncopeptides Ab | Novel treatments |
| GB202109894D0 (en) | 2021-07-08 | 2021-08-25 | Oncopeptides Ab | Novel treatments |
| US20240307480A1 (en) | 2021-07-08 | 2024-09-19 | Oncopeptides Ab | Melflufen for use in the treatment of multiple myeloma |
| GB202204171D0 (en) | 2022-03-24 | 2022-05-11 | Oncopeptides Ab | Novel formulations |
| WO2026057823A1 (en) * | 2024-09-13 | 2026-03-19 | Oncopeptides Ab | Bis-chloroethylamino derivatives for treating leukemia |
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| SE0002202D0 (sv) | 2000-06-13 | 2000-06-13 | Karolinska Innovations Ab | New peptides |
| NZ591615A (en) | 2008-09-18 | 2012-07-27 | Auspex Pharmaceuticals Inc | Benzoquinoline inhibitors of vesicular monoamine transporter 2 |
| US20120003330A1 (en) | 2010-06-01 | 2012-01-05 | Auspex Pharmaceuticals, Inc. | Benzoquinolone inhibitors of vmat2 |
| SI3228319T1 (sl) | 2011-04-28 | 2020-10-30 | Oncopeptides Ab | Liofiliziran pripravek citotoksičnih dipeptidov |
| JP6362601B2 (ja) | 2012-09-18 | 2018-07-25 | オースペックス・ファーマシューティカルズ・インコーポレイテッドＡｕｓｐｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 小胞モノアミン輸送体２の重水素化ベンゾキノリン阻害剤の製剤薬物動態 |
| JP6284945B2 (ja) * | 2012-10-26 | 2018-02-28 | オンコペプティデス エービーＯｎｃｏｐｅｐｔｉｄｅｓ ＡＢ | メルファランフルフェナミドの凍結乾燥製剤 |
| EA202091397A1 (ru) | 2013-01-31 | 2020-09-04 | Ауспекс Фармацетикалс, Инк. | Бензохинолоновые ингибиторы vmat2 |
| JP6704252B2 (ja) | 2013-02-05 | 2020-06-03 | テバ・ファーマシューティカルズ・インターナショナル・ゲーエムベーハーＴｅｖａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｔｅｒｎａｔｉｏｎａｌ ＧｍｂＨ | 位置特異的非対称重水素富化カテコールアミン誘導体および前記化合物を含有する医薬 |
| AU2014357518A1 (en) | 2013-12-03 | 2016-06-09 | Auspex Pharmaceuticals, Inc. | Methods of manufacturing benzoquinoline compounds |
| CN104725380B (zh) * | 2013-12-18 | 2019-06-28 | 康塞特医药品有限公司 | 卢索替尼的氘代衍生物 |
| PL3265085T3 (pl) | 2015-03-06 | 2022-11-07 | Auspex Pharmaceuticals, Inc. | Sposoby leczenia zaburzeń związanych z nieprawidłowymi ruchami mimowolnymi |
| GB201507903D0 (en) | 2015-05-08 | 2015-06-24 | Oncopeptides Ab | Process for preparation of nitrogen mustard derivatives |
| GB201521217D0 (en) * | 2015-12-01 | 2016-01-13 | Oncopeptides Ab | Dosage regimens |
-
2019
- 2019-10-17 WO PCT/EP2019/078250 patent/WO2020079165A1/en not_active Ceased
- 2019-10-17 CA CA3116198A patent/CA3116198A1/en active Pending
- 2019-10-17 SG SG11202103726RA patent/SG11202103726RA/en unknown
- 2019-10-17 KR KR1020217011490A patent/KR102848971B1/ko active Active
- 2019-10-17 EP EP19790194.5A patent/EP3866931B1/en active Active
- 2019-10-17 MX MX2021004474A patent/MX2021004474A/es unknown
- 2019-10-17 FI FIEP19790194.5T patent/FI3866931T3/fi active
- 2019-10-17 MA MA053904A patent/MA53904A/fr unknown
- 2019-10-17 AU AU2019362389A patent/AU2019362389B2/en active Active
- 2019-10-17 BR BR112021007060-5A patent/BR112021007060A2/pt unknown
- 2019-10-17 DK DK19790194.5T patent/DK3866931T3/da active
- 2019-10-17 ES ES19790194T patent/ES2942468T3/es active Active
- 2019-10-17 IL IL282231A patent/IL282231B2/en unknown
- 2019-10-17 HU HUE19790194A patent/HUE061801T2/hu unknown
- 2019-10-17 JP JP2021521145A patent/JP7603199B2/ja active Active
- 2019-10-17 CN CN201980068384.1A patent/CN112930214B/zh active Active
- 2019-10-17 PL PL19790194.5T patent/PL3866931T3/pl unknown
- 2019-10-17 US US17/286,002 patent/US12152087B2/en active Active
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2021
- 2021-04-15 ZA ZA2021/02492A patent/ZA202102492B/en unknown
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2024
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- 2024-10-16 US US18/917,773 patent/US20250115637A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| MA53904A (fr) | 2021-08-25 |
| US12152087B2 (en) | 2024-11-26 |
| SG11202103726RA (en) | 2021-05-28 |
| CN112930214B (zh) | 2025-05-16 |
| US20250115637A1 (en) | 2025-04-10 |
| AU2019362389A1 (en) | 2021-06-03 |
| JP2024150488A (ja) | 2024-10-23 |
| JP2022512736A (ja) | 2022-02-07 |
| CA3116198A1 (en) | 2020-04-23 |
| MX2021004474A (es) | 2021-08-24 |
| KR20210078487A (ko) | 2021-06-28 |
| BR112021007060A2 (pt) | 2021-07-20 |
| IL282231B2 (en) | 2025-07-01 |
| WO2020079165A1 (en) | 2020-04-23 |
| US20210388024A1 (en) | 2021-12-16 |
| IL282231A (en) | 2021-05-31 |
| FI3866931T3 (fi) | 2023-05-10 |
| IL282231B1 (en) | 2025-03-01 |
| AU2019362389B2 (en) | 2024-12-12 |
| HUE061801T2 (hu) | 2023-08-28 |
| EP3866931B1 (en) | 2023-02-15 |
| CN112930214A (zh) | 2021-06-08 |
| DK3866931T3 (da) | 2023-04-24 |
| ZA202102492B (en) | 2024-04-24 |
| KR102848971B1 (ko) | 2025-08-21 |
| PL3866931T3 (pl) | 2023-06-19 |
| EP3866931A1 (en) | 2021-08-25 |
| JP7603199B2 (ja) | 2024-12-20 |
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