RU2019101651A - Соединения на основе платины и липидов и наночастицы - Google Patents
Соединения на основе платины и липидов и наночастицы Download PDFInfo
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- RU2019101651A RU2019101651A RU2019101651A RU2019101651A RU2019101651A RU 2019101651 A RU2019101651 A RU 2019101651A RU 2019101651 A RU2019101651 A RU 2019101651A RU 2019101651 A RU2019101651 A RU 2019101651A RU 2019101651 A RU2019101651 A RU 2019101651A
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- 150000001875 compounds Chemical class 0.000 title claims 17
- 239000002105 nanoparticle Substances 0.000 title claims 15
- 150000002632 lipids Chemical class 0.000 title claims 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 21
- 238000000034 method Methods 0.000 claims 15
- 229910052697 platinum Inorganic materials 0.000 claims 8
- 206010028980 Neoplasm Diseases 0.000 claims 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 6
- 201000011510 cancer Diseases 0.000 claims 5
- 150000002327 glycerophospholipids Chemical class 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 150000003058 platinum compounds Chemical class 0.000 claims 4
- 229920001223 polyethylene glycol Polymers 0.000 claims 4
- 150000003135 prenol lipids Chemical class 0.000 claims 4
- 150000003408 sphingolipids Chemical class 0.000 claims 4
- 239000003381 stabilizer Substances 0.000 claims 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- 239000002202 Polyethylene glycol Substances 0.000 claims 3
- JLPULHDHAOZNQI-JLOPVYAASA-N [(2r)-3-hexadecanoyloxy-2-[(9e,12e)-octadeca-9,12-dienoyl]oxypropyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC JLPULHDHAOZNQI-JLOPVYAASA-N 0.000 claims 3
- 229910052799 carbon Inorganic materials 0.000 claims 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims 3
- 229960004316 cisplatin Drugs 0.000 claims 3
- 125000005456 glyceride group Chemical group 0.000 claims 3
- 229960001756 oxaliplatin Drugs 0.000 claims 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 claims 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical group [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
- 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 claims 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 150000001720 carbohydrates Chemical class 0.000 claims 2
- 235000014633 carbohydrates Nutrition 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims 2
- -1 diglyceride Chemical class 0.000 claims 2
- MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 229910017053 inorganic salt Inorganic materials 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- 125000004001 thioalkyl group Chemical group 0.000 claims 2
- 150000003573 thiols Chemical class 0.000 claims 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 241000196324 Embryophyta Species 0.000 claims 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims 1
- 229930186217 Glycolipid Natural products 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 206010039491 Sarcoma Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 229930182558 Sterol Natural products 0.000 claims 1
- 208000024313 Testicular Neoplasms Diseases 0.000 claims 1
- 206010057644 Testis cancer Diseases 0.000 claims 1
- 238000009825 accumulation Methods 0.000 claims 1
- 235000019270 ammonium chloride Nutrition 0.000 claims 1
- 229940045985 antineoplastic platinum compound Drugs 0.000 claims 1
- 239000003963 antioxidant agent Substances 0.000 claims 1
- 230000003078 antioxidant effect Effects 0.000 claims 1
- 239000002216 antistatic agent Substances 0.000 claims 1
- 210000001367 artery Anatomy 0.000 claims 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims 1
- 239000003613 bile acid Substances 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 230000004700 cellular uptake Effects 0.000 claims 1
- 239000011248 coating agent Substances 0.000 claims 1
- 230000001268 conjugating effect Effects 0.000 claims 1
- 239000008121 dextrose Substances 0.000 claims 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 1
- 239000002270 dispersing agent Substances 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 239000003995 emulsifying agent Substances 0.000 claims 1
- 210000003238 esophagus Anatomy 0.000 claims 1
- 239000000796 flavoring agent Substances 0.000 claims 1
- 235000013355 food flavoring agent Nutrition 0.000 claims 1
- 235000003599 food sweetener Nutrition 0.000 claims 1
- 201000010175 gallbladder cancer Diseases 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 1
- 239000003979 granulating agent Substances 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 201000005787 hematologic cancer Diseases 0.000 claims 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 239000000314 lubricant Substances 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 239000008176 lyophilized powder Substances 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims 1
- 235000019799 monosodium phosphate Nutrition 0.000 claims 1
- 210000000214 mouth Anatomy 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 150000003904 phospholipids Chemical class 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 239000004014 plasticizer Substances 0.000 claims 1
- 239000001103 potassium chloride Substances 0.000 claims 1
- 235000011164 potassium chloride Nutrition 0.000 claims 1
- 239000003755 preservative agent Substances 0.000 claims 1
- 230000002335 preservative effect Effects 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 235000002639 sodium chloride Nutrition 0.000 claims 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims 1
- 238000005563 spheronization Methods 0.000 claims 1
- 150000003431 steroids Chemical class 0.000 claims 1
- 150000003432 sterols Chemical class 0.000 claims 1
- 235000003702 sterols Nutrition 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000004094 surface-active agent Substances 0.000 claims 1
- 239000000375 suspending agent Substances 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 239000003765 sweetening agent Substances 0.000 claims 1
- 201000003120 testicular cancer Diseases 0.000 claims 1
- 239000011782 vitamin Substances 0.000 claims 1
- 229940088594 vitamin Drugs 0.000 claims 1
- 229930003231 vitamin Natural products 0.000 claims 1
- 235000013343 vitamin Nutrition 0.000 claims 1
- 150000003722 vitamin derivatives Chemical class 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
- A61K47/551—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/282—Platinum compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/554—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
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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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
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- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Botany (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (66)
1. Соединение формулы (VIII):
Q-линкер-липид (VIII)
где
Q представляет собой:
(i) 
,
где X представляет собой NH или N(CH2COO-); и
Z представляет собой содержащее платину соединение, при этом платина образует часть цикла;
(ii) 
,
где X представляет собой S+, C, S+=O, N+H или P=O;
X1 представляет собой –CH-, -CH2- или -CH2O-;
X2 представляет собой C=O; и
Z представляет собой содержащее платину соединение, при этом платина образует часть цикла;
(iii) 
,
где X1 представляет собой (CH2)n;
X2 представляет собой C=O;
Z представляет собой содержащее платину соединение, где платина образует часть цикла; и
n равно 0, 1 или 2;
(iv) 
,
где R1, R2 и R3 независимо представляют собой галоген, амино, алкиламино, диалкиламино, гидроксил, тиол, тиоалкил, O-ацил, -линкер-липид или их комбинацию; или
(v) 
,
где R1, R2, R3, R4 и R5 независимо представляют собой галоген, амино, алкиламино, диалкиламино, гидроксил, тиол, тиоалкил, O-ацил, -линкер-липид или их комбинацию;
линкер представляет собой:
(i) —X-CH2-X2-X1—, где:
X представляет собой NH;
X1 представляет собой C(O)O, C(O)NH, O(CH2)-O, NH, or O;
X2 представляет собой (CH2)n or C(O); and
n равно 0, 1, 2, 3, 4 или 5;
(ii) —(CH2)nO—, —(CH2)nNHC(O)O—, —(CH2)nOC(O)NH—, —(CH2)nC(O)NH(CH2)mO—, —(CH2)nO(CH2)mO—, —(CH2)nC(O)—, —(CH2)nNHC(O)(CH2)mO— или —(CH2)nC(O)O—; где n и m независимо представляют собой 0, 1, 2, 3, 4 или 5;
(iii —X3-X4X5-X6—, где:
X3 is CH, CH2 или O; и
X
4
, X
5
and X
6
независимо представляют собой —CH
2
O— или O; или
(iv) или комбинацию (i)-(iii);
липид представляет собой жир, воск, стерин, стероид, желчную кислоту, жирорастворимый витамин, моноглицерид, диглицерид, фосфолипид, гликолипид, сульфолипид, аминолипид, хромолипид, глицерофосфолипид, сфинголипид, преноллипид, сахаролипид, поликетид, жирную кислоту или их комбинацию.
2. Соединение по п.1, где соединение представлено формулой (II)
где:
X представляет собой NH or N-CH2C(O)O¯;
X1 представляет собой -(CH2)nO-, -(CH2)nNHC(O)O-, -(CH2)nC(O)NH(CH2)nO-, -(CH2)nO(CH2)nO-, -(CH2)nC(O)-, -(CH2)nNHC(O)(CH2)nO-, or -(CH2)nC(O)O-;
Z представляет собой содержащее платину соединение, где платина образует часть цикла в формуле II; и
n равно 0, 1, or 2.
3. Способ получения соединения по п.1 или 2, включающий
(а) взаимодействие липида с линкером, с образованием первого соединения;
(b) необязательно, взаимодействие первого соединения со стадии (a) с карбонильной частью с образованием второго соединения; и
(с) конъюгацию первого соединения со стадии (a) или второго соединения со стадии (b) с платиновой частью.
4. Наночастица, содержащая соединение по п. 1 или 2.
5. Наночастица по п.4, где наночастица дополнительно включает солипид и/или стабилизатор.
6. Наночастица по п.5, в которой отношение соединения к солипиду и/или стабилизатору составляет от 99:1 дo 1:99 (мас./мас.), (моль/моль) или (об./об.).
7. Наночастица по п.5, где наночастица включает соевый фосфатидилхолин и 1,2-дистеароил-sn-глицеро-3-фосфоэтаноламин-N-[метокси(полиэтиленгликоль)-2000] в качестве солипидов, и отношение соединения к солипидам составляет от 1:1:0,01 до 1:4:3 (мас./мас.), (моль/моль) или (об./об.).
8. Наночастица по п.4, где наночастица имеет повышенное клеточное поглощение платины в раковых клетках по сравнению с цисплатином или оксалиплатином.
9. Наночастица по п.4, где наночастица имеет большее накопление платины в опухоли по сравнению с цисплатином или оксалиплатином в дозировке, эквивалентной количеству цисплатина или оксалиплатина.
10. Фармацевтическая композиция для лечения или борьбы с развитием рака, включающая наночастицу по любому из пп. 4-9.
11. Фармацевтическая композиция по п.10, в которой эксципиент представляет собой гранулирующий агент, связующее, лубрикант, диспергирующий агент, подслащивающее вещество, глидант, антиадгезив, антистатик, поверхностно-активное вещество, антиоксидант, камедь, средство для покрытия, краситель, корригент, пластификатор, консервант, суспендирующее вещество, эмульгатор, растительный целлюлозный материал, агент сферонизации или их комбинацию.
12. Фармацевтическая композиция по п.10 или 11, где композиция составлена в стандартную лекарственную форму, представляющую собой препарат для инъекций, таблетку, лиофилизованный порошок, липосомальную суспензию или их комбинацию.
13. Способ лечения или борьбы с развитием рака у пациента, включающий введение пациенту терапевтически эффективного количества соединения по п.1 или 2, или наночастиц по любому из пп. 4-9.
14. Способ по п.13, где рак представляет собой рак молочной железы, рак головы и шеи, рак яичников, тестикулярный рак, рак предстательной железы, рак полости рта и пищевода, рак желудочно-кишечного тракта, рак печени, рак желчного пузыря, рак легких, меланому, рак кожи, саркому, рак крови, рак головного мозга, глиобластому, опухоли нейроэктодермального происхождения или их комбинацию.
15. Способ по п.13, где указанное введение осуществляют внутривенно, внутрисуставно, в панкреатодуоденальную артерию, интраперитонеально, гепатопортально, внутримышечно или их комбинацией.
16. Способ получения наночастицы по п.4, включающий взаимодействие соединения платины, где соединение платины включает платиновую часть и липид, соединенный с указанной платиновой частью, с солипидом в присутствии растворителя, с образованием наночастицы.
17. Способ по п.16, где соединение платины получают способом по п.3.
18. Способ по п. 16 или 17, где растворитель представляет собой хлороформ, метанол, дихлорметан, этанол или их комбинацию.
19. Способ по п. 16 или 17, где солипид представляет собой соевый фосфатидилхолин (полностью гидрированный), 1,2-дистеароил-sn-глицеро-3-фосфоэтаноламин-N-[метокси(полиэтиленгликоль)-2000], диолеоилфосфатидилхолин (DOPC), 1,2-дистеароил-sn-глицеро-3-фосфоэтаноламин-PEG-OMe (DSPE-PEG-OMe), диолеоилфосфатидилэтаноламин (DOPE) или их комбинацию.
20. Способ по п.16, дополнительно включающий сушку, инкубацию и необязательное добавление стабилизатора.
21. Способ по п.20, где стабилизатор представляет собой DSPE-ПЭГ-OMe, DSPE-ПЭГ-NH2, ПЭГ, неорганическую соль, углевод или их комбинацию.
22. Способ по п.21, где неорганическая соль представляет собой хлорид аммония, хлорид калия, хлорид натрия, динатрийгидрофосфат, дигидрофосфат натрия или их комбинацию.
23. Способ по п.21, где углевод представляет собой глюкозу, декстрозу или их комбинацию.
24. Способ по пп. 16-23, где солипид представляет собой соевый фосфатидилхолин и 1,2-дистеароил-sn-глицеро-3-фосфоэтаноламин-N-[метокси(полиэтиленгликоль)-2000].
25. Способ по пп. 16-24, где отношение соединения платины и солипидов составляет от 1:1:0,01 до 1:4:3 (мас./мас.), (моль/моль) или (об./об.).
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| KR102085190B1 (ko) * | 2015-04-13 | 2020-03-05 | 더 유니버시티 오브 홍콩 | Oled 어플리케이션용 금 착물 |
| US11358978B2 (en) * | 2015-05-19 | 2022-06-14 | Akamara Therapeutics, Inc. | Process for preparing supramolecular platinum-based compounds |
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| KR20180105723A (ko) | 2016-02-11 | 2018-09-28 | 인빅터스 온콜로지 피비티. 엘티디. | 세포 신호전달 억제제, 이의 제형 및 이의 방법 |
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