RU2016118771A - Со-кристаллы и содержащие их фармацевтические композиции - Google Patents
Со-кристаллы и содержащие их фармацевтические композиции Download PDFInfo
- Publication number
- RU2016118771A RU2016118771A RU2016118771A RU2016118771A RU2016118771A RU 2016118771 A RU2016118771 A RU 2016118771A RU 2016118771 A RU2016118771 A RU 2016118771A RU 2016118771 A RU2016118771 A RU 2016118771A RU 2016118771 A RU2016118771 A RU 2016118771A
- Authority
- RU
- Russia
- Prior art keywords
- crystal
- mass
- methyl
- adipic acid
- compound
- Prior art date
Links
- 239000013078 crystal Substances 0.000 title claims 50
- 239000008194 pharmaceutical composition Substances 0.000 title claims 12
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims 50
- 239000001361 adipic acid Substances 0.000 claims 25
- 235000011037 adipic acid Nutrition 0.000 claims 25
- 150000001875 compounds Chemical class 0.000 claims 24
- 238000000034 method Methods 0.000 claims 19
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 12
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 8
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 8
- 230000005496 eutectics Effects 0.000 claims 6
- 239000008247 solid mixture Substances 0.000 claims 6
- 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 claims 5
- 239000005711 Benzoic acid Substances 0.000 claims 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 4
- 235000010233 benzoic acid Nutrition 0.000 claims 4
- 239000001530 fumaric acid Substances 0.000 claims 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 4
- 239000011976 maleic acid Substances 0.000 claims 4
- 239000001384 succinic acid Substances 0.000 claims 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 229910052805 deuterium Inorganic materials 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- 239000000126 substance Substances 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 238000011319 anticancer therapy Methods 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 238000002156 mixing Methods 0.000 claims 2
- PEACIOGDEQRHFA-CQSZACIVSA-N n-methyl-8-[(2s)-1-[[6-(2-methylpyrimidin-5-yl)pyrimidin-4-yl]amino]propan-2-yl]quinoline-4-carboxamide Chemical compound C([C@@H](C)C1=C2N=CC=C(C2=CC=C1)C(=O)NC)NC(N=CN=1)=CC=1C1=CN=C(C)N=C1 PEACIOGDEQRHFA-CQSZACIVSA-N 0.000 claims 2
- 230000000704 physical effect Effects 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- LEWDKQKVAFOMPI-UHFFFAOYSA-N quinoline-4-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CC=NC2=C1 LEWDKQKVAFOMPI-UHFFFAOYSA-N 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- -1 6 -deutero- [4,5'-bipyrimidine] -6-yl Chemical group 0.000 claims 1
- 241000260897 Acidota Species 0.000 claims 1
- 230000005778 DNA damage Effects 0.000 claims 1
- 231100000277 DNA damage Toxicity 0.000 claims 1
- 239000012623 DNA damaging agent Substances 0.000 claims 1
- 238000005481 NMR spectroscopy Methods 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000003181 co-melting Methods 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 238000001125 extrusion Methods 0.000 claims 1
- 238000000227 grinding Methods 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 239000000155 melt Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000003389 potentiating effect Effects 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 230000001235 sensitizing effect Effects 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 239000007790 solid phase Substances 0.000 claims 1
- 238000004611 spectroscopical analysis Methods 0.000 claims 1
- 238000000859 sublimation Methods 0.000 claims 1
- 238000011285 therapeutic regimen Methods 0.000 claims 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- 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
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
- C07C55/02—Dicarboxylic acids
- C07C55/10—Succinic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
- C07C55/02—Dicarboxylic acids
- C07C55/14—Adipic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
- C07C57/13—Dicarboxylic acids
- C07C57/145—Maleic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
- C07C57/13—Dicarboxylic acids
- C07C57/15—Fumaric acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
- C07C59/265—Citric acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
- C07C63/04—Monocyclic monocarboxylic acids
- C07C63/06—Benzoic acid
- C07C63/08—Salts thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N2005/1092—Details
- A61N2005/1098—Enhancing the effect of the particle by an injected agent or implanted device
-
- 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
-
- 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
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Claims (53)
1. Со-кристалл, содержащий соединение формулы:
и образователь со-кристалла, выбираемый из адипиновой кислоты, лимонной кислоты, фумаровой кислоты, малеиновой кислоты, янтарной кислоты или бензойной кислоты, где каждый из R1 и R2 означает водород или дейтерий.
2. Со-кристалл по п.1, где образователь со-кристалла представляет собой адипиновую кислоту и молярное соотношение адипиновой кислоты к соединению формулы (I) составляет примерно от 1 до 2.
3. Со-кристалл по п.2, где соединение формулы (I) представляет собой (S)-N-метил-8-(1-((2’-метил-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамид.
4. Со-кристалл по п.2, где соединение формулы (I) представляет собой (S)-N-метил-8-(1-((2’-метил-4’,6’-дидейтеро-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамид.
5. Со-кристалл по п.3 или 4, имеющий пики отражения в порошковой рентгенограмме при примерно 6,46, 7,91, 11,92, 12,26, 12,99, 14,19, 18,68 и 19,07 θ.
6. Со-кристалл по п.3 или 4, имеющий DSC-пик на его DSC-термограмме при температуре примерно 195°С и примерно 245°С.
7. Со-кристалл по п.3 или 4, где со-кристалл находится в полиморфной форме А.
8. Со-кристалл по п.5, где полиморфная форма А характеризуется пиками 13С спектроскопии ядерного магнитного резонанса твердого тела при примерно 117,1, 96,8, 95,7, 27,6, 14,8 част./млн.
9. Со-кристалл по п.7, где полиморфная форма А характеризуется пиками 13С спектроскопии ядерного магнитного резонанса твердого тела при примерно 161,6, 154,5, 117,1, 96,8, 95,7, 51,5, 50,2, 27,6, 25,6, 18,5 и 14,8 част./млн.
10. Со-кристалл по п.7, где полиморфная форма А характеризуется пиками 13С спектроскопии ядерного магнитного резонанса твердого тела при примерно 179,4, 168,4, 161,6, 158,3, 154,5, 147,8, 145,7, 143,2, 141,8, 124,6, 117,1, 96,8, 95,7, 51,5, 50,2, 31,2, 30,1, 27,6, 25,6, 18,5 и 14,8 част./млн.
11. Со-кристалл по п.3 или 4, где со-кристалл находится в полиморфной форме В.
12. Со-кристалл по п.11, где полиморфная форма В характеризуется пиками 13С спектроскопии ядерного магнитного резонанса твердого тела при примерно 117,9, 97,3, 94,0, 26,7 и 15,7 част./млн.
13. Со-кристалл по п.11, где полиморфная форма В характеризуется пиками 13С спектроскопии ядерного магнитного резонанса твердого тела при примерно 161,7, 153,8, 117,9, 97,3, 94,0, 50,7, 25,3, 26,7, 18,8 и 15,7 част./млн.
14. Со-кристалл по п.11, где полиморфная форма В характеризуется пиками 13С спектроскопии ядерного магнитного резонанса твердого тела при примерно 179,1, 168,3, 158,1, 147,2, 142,4, 125,8, 124,5, 117,9, 97,3, 94,0, 32,3, 30,1, 26,7 и 15,7 част./млн.
15. Со-кристалл по п.3 или 4, где со-кристалл представляет собой смесь полиморфной формы А и формы В.
16. Фармацевтическая композиция, содержащая со-кристалл, где со-кристалл включает соединение формулы:
и образователь со-кристалла, выбираемый из адипиновой кислоты, лимонной кислоты, фумаровой кислоты, малеиновой кислоты, янтарной кислоты или бензойной кислоты, где каждый из R1 и R2 означает водород или дейтерий.
17. Фармацевтическая композиция по п.16, где соединение формулы I представляет собой (S)-N-метил-8-(1-((2’-метил-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамид и это соединение и адипиновая кислота, в качестве образователя со-кристалла, вместе находятся в кристаллической форме.
18. Фармацевтическая композиция по п.16, где соединение формулы I представляет собой (S)-N-метил-8-(1-((2’-метил-4’,6’-дидейтеро-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамид и соединение и адипиновая кислота, в качестве образователя со-кристалла, вместе находятся в кристаллической форме.
19. Фармацевтическая композиция по п.17 или 18, где молярное соотношение соединения формулы I к адипиновой кислоте составляет примерно от 2 до 1.
20. Фармацевтическая композиция по любому одному из пп.16-19, содержащая, далее, разбавитель, растворитель, эксципиент, носитель или солюбилизирующий агент.
21. Фармацевтическая композиция по любому одному из пп.16-20, содержащая, далее, дополнительное количество адипиновой кислоты.
22. Фармацевтическая композиция по п.19, где общее массовое соотношение соединения формулы I к адипиновой кислоте находится в диапазоне от примерно 85% масс. : 15% масс. до примерно 60% масс. : 40% масс.
23. Фармацевтическая композиция по п.22, где общее массовое соотношение соединения формулы I к адипиновой кислоте находится в диапазоне от примерно 70% масс. : 30% масс. до примерно 60% масс. : 40% масс.
24. Способ получения со-кристалла, включающий: измельчение, нагревание, со-сублимирование, со-расплавление или контактирование или (S)-N-метил-8-(1-((2’-метил-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамида или (S)-N-метил-8-(1-((2’-метил-4’,6’-дидейтеро-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамида с образователем со-кристалла, при условиях кристаллизации, для того, чтобы образовать со-кристалл в твердой фазе, где образователь со-кристалла выбирают из группы, состоящей из адипиновой кислоты, лимонной кислоты, фумаровой кислоты, малеиновой кислоты, янтарной кислоты или бензойной кислоты.
25. Способ модулирования представляющих интерес химических или физических свойств со-кристалла, включающий: (а) определение представляющих интерес химических или физических свойств или (S)-N-метил-8-(1-((2’-метил-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамида или (S)-N-метил-8-(1-((2’-метил-4’,6’-дидейтеро-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамида и образователя со-кристалла, (b) определение мольной доли или (S)-N-метил-8-(1-((2’-метил-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамида или (S)-N-метил-8-(1-((2’-метил-4’,6’-дидейтеро-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамида и образователя со-кристалла, что может приводить, в результате, к желательной модуляции представляющих интерес химических или физических свойств, и (с) получение со-кристалла с мольной долей, определенной на стадии (b).
26. Способ получения со-кристалла, включающий получение предсуществующего со-кристалла, в качестве затравки для получения со-кристалла, где предсуществующий со-кристалл включает: (i) или (S)-N-метил-8-(1-((2’-метил-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамид или (S)-N-метил-8-(1-((2’-метил-4’,6’-дидейтеро-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамид; и (ii) адипиновую кислоту; и получаемый со-кристалл включает: (i) активный ингредиент, выбираемый из (S)-N-метил-8-(1-((2’-метил-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамида или (S)-N-метил-8-(1-((2’-метил-4’,6’-дидейтеро-[4,5’-бипиримидин]-6-ил)амино)пропан-2-ил)хинолин-4-карбоксамида; и (ii) образователь со-кристалла, выбираемый из адипиновой кислоты.
27. Эвтектическая твердая композиция, включающая: (а) со-кристалл, содержащий соединение формулы (I):
и образователь со-кристалла, выбираемый из адипиновой кислоты, где каждый из R1 и R2 означает водород или дейтерий, и где молярное соотношение соединения формулы I к адипиновой кислоте составляет от примерно 2 до 1; и (b) адипиновую кислоту.
28. Эвтектическая твердая композиция по п.27, где общее массовое соотношение соединения формулы I к адипиновой кислоте находится в диапазоне от примерно 70% масс. : 30% масс. до примерно 60% масс. : примерно 40% масс.
29. Эвтектическая твердая композиция по п.28, где общее массовое соотношение соединения формулы I к адипиновой кислоте находится в диапазоне примерно 65% масс. : 35% масс.
30. Способ получения со-кристалла, включающий: смешивание соединения формулы (I):
с адипиновой кислотой, лимонной кислотой, фумаровой кислотой, малеиновой кислотой, янтарной кислотой или бензойной кислотой, при повышенной температуре, до образования со-кристалла.
31. Способ по п.30, где соединение формулы (I) смешивают с адипиновой кислотой при повышенной температуре в диапазоне от примерно 110°С до примерно 195°С, до образования со-кристалла.
32. Способ по п.31, где повышенная температура находится в диапазоне от примерно 130°С до примерно 180°С.
33. Способ по п.32, где повышенная температура находится в диапазоне от примерно 140°С до примерно 160°С.
34. Способ по любому одному из пп.30-33, где смешивают от 10% масс. до примерно 85% масс. соединения (I) и от примерно 90% масс. до 15% масс. адипиновой кислоты.
35. Способ по п.34, где соединение (I) составляет от примерно 30% масс. до примерно 80% масс. и адипиновая кислота составляет от примерно 70% масс. до примерно 20% масс.
36. Способ по п.35, где соединение (I) составляет от примерно 50% масс. до примерно 80% масс. и адипиновая кислота составляет от примерно 50% масс. до примерно 20% масс.
37. Способ по п.36, где соединение (I) составляет от примерно 60% масс. до 70% масс. и адипиновая кислота составляет от примерно 40% масс. до примерно 30% масс.
38. Способ по п.37, где соединение (I) составляет примерно 65% масс. и адипиновая кислота составляет примерно 35% масс.
39. Способ по п.30, где смешивание соединения (I) c образователем со-кристалла при повышенной температуре пригодно для использования установки для экструзии из расплава.
40. Способ сенсибилизации клетки с помощью агента, который вызывает повреждение ДНК, включающий введение в контакт клетки с со-кристаллом по любому одному из пп.1-15, с фармацевтической композицией по любому одному из пп.16-23 или с эвтектической твердой композицией по п.27.
41. Способ потенцирования терапевтического режима для лечения ракового заболевания у пациента, включающий введение вышеуказанному пациенту эффективного количества со-кристалла по любому одному из пп.1-15, фармацевтической композиции по любому одному из пп.16-23 или эвтектической твердой композиции по п.27.
42. Способ лечения ракового заболевания у пациента, включающий введение вышеуказанному пациенту эффективного количества со-кристалла по любому одному из пп.1-15, фармацевтической композиции по любому одному из пп.16-23 или эвтектической твердой композиции по п.27.
43. Способ по п.42, далее, включающий введение дополнительной противораковой терапии.
44. Способ по п.43, где дополнительную противораковую терапию выбирают из противоракового агента или радиационной терапии, или обоих.
45. Способ по п.44, где противораковый агент выбирают из повреждающего ДНК агента.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361892002P | 2013-10-17 | 2013-10-17 | |
US61/892,002 | 2013-10-17 | ||
PCT/US2014/061102 WO2015058067A1 (en) | 2013-10-17 | 2014-10-17 | Co-crystals of (s)-n-methyl-8-(1-((2'-methyl-[4,5'-bipyrimidin]-6-yl)amino)propan-2-yl)quinoline-4-carboxamide and deuterated derivatives thereof as dna-pk inhibitors |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2018143803A Division RU2018143803A (ru) | 2013-10-17 | 2014-10-17 | Со-кристаллы и содержащие их фармацевтические композиции |
Publications (3)
Publication Number | Publication Date |
---|---|
RU2016118771A true RU2016118771A (ru) | 2017-11-22 |
RU2016118771A3 RU2016118771A3 (en) | 2018-07-10 |
RU2675270C2 RU2675270C2 (ru) | 2018-12-18 |
Family
ID=51904228
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2018143803A RU2018143803A (ru) | 2013-10-17 | 2014-10-17 | Со-кристаллы и содержащие их фармацевтические композиции |
RU2016118771A RU2675270C2 (ru) | 2013-10-17 | 2014-10-17 | Сокристаллы и содержащие их фармацевтические композиции |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2018143803A RU2018143803A (ru) | 2013-10-17 | 2014-10-17 | Со-кристаллы и содержащие их фармацевтические композиции |
Country Status (26)
Country | Link |
---|---|
US (2) | US10039761B2 (ru) |
EP (2) | EP3057953B1 (ru) |
JP (2) | JP6408569B2 (ru) |
KR (1) | KR102411227B1 (ru) |
CN (2) | CN105814036B (ru) |
AU (2) | AU2014337154B2 (ru) |
BR (1) | BR112016008452B1 (ru) |
CA (1) | CA2927631C (ru) |
CL (1) | CL2016000916A1 (ru) |
DK (2) | DK3057953T3 (ru) |
ES (2) | ES2802296T3 (ru) |
HR (2) | HRP20181841T1 (ru) |
HU (2) | HUE041877T2 (ru) |
IL (1) | IL245117B (ru) |
LT (2) | LT3424920T (ru) |
MX (1) | MX361488B (ru) |
PE (1) | PE20161022A1 (ru) |
PL (2) | PL3424920T3 (ru) |
PT (2) | PT3057953T (ru) |
RS (2) | RS57969B1 (ru) |
RU (2) | RU2018143803A (ru) |
SG (1) | SG11201602962PA (ru) |
SI (2) | SI3424920T1 (ru) |
UA (1) | UA120915C2 (ru) |
WO (1) | WO2015058067A1 (ru) |
ZA (1) | ZA201602777B (ru) |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT2841428T (pt) | 2012-04-24 | 2018-11-29 | Vertex Pharma | Inibidores de adn-pk |
EP3985003B1 (en) | 2013-03-12 | 2023-08-09 | Vertex Pharmaceuticals Incorporated | Dna-pk inhibitors |
CN105814036B (zh) * | 2013-10-17 | 2018-10-26 | 沃泰克斯药物股份有限公司 | 作为dna-pk抑制剂的共晶 |
WO2015188073A1 (en) | 2014-06-06 | 2015-12-10 | Research Triangle Institute | Apelin receptor (apj) agonists and uses thereof |
EP3297624B1 (en) | 2015-05-18 | 2021-03-03 | Syn-Nat Products Enterprise LLC | A pharmaceutical co-crystal and use thereof |
AU2016279096B2 (en) | 2015-06-19 | 2021-01-07 | Syn-Nat Products Enterprise LLC | Composition containing carboplatin and use |
EP3297636B1 (en) | 2015-06-19 | 2021-02-17 | Syn-Nat Products Enterprise LLC | Pharmaceutical composition of carboplatin based co-crystals and use thereof |
CN116854745A (zh) | 2015-06-25 | 2023-10-10 | 新纳特产品公司 | 药物共晶组合物及其用途 |
CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
RU2021133849A (ru) | 2015-12-09 | 2022-03-21 | Рисерч Трайэнгл Инститьют | Улучшенные агонисты апелинового рецептора (apj) и их использование |
US11008277B2 (en) * | 2016-06-13 | 2021-05-18 | Syneurx International (Taiwan) Corp. | Co-crystals of sodium benzoate and uses thereof |
AU2017295720B2 (en) * | 2016-07-13 | 2021-07-22 | Vertex Pharmaceuticals Incorporated | Methods, compositions and kits for increasing genome editing efficiency |
WO2018053222A1 (en) | 2016-09-16 | 2018-03-22 | Research Traingle Institute | Tetrahydroisoquinoline kappa opioid antagonists |
KR20190062485A (ko) | 2016-09-27 | 2019-06-05 | 버텍스 파마슈티칼스 인코포레이티드 | Dna-손상제 및 dna-pk 저해제의 조합을 사용한 암 치료 방법 |
MA46540A (fr) | 2016-10-12 | 2019-08-21 | Res Triangle Inst | Agonistes du récepteur de l'apéline (apj) hétérocyclique et leurs utilisations |
JP7113826B2 (ja) * | 2016-12-19 | 2022-08-05 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | プロテインキナーゼ阻害剤および追加的化学療法剤の組み合わせ |
CA3063632A1 (en) | 2017-05-18 | 2018-11-22 | Idorsia Pharmaceuticals Ltd | Benzofurane and benzothiophene derivatives as pge2 receptor modulators |
TW201900180A (zh) | 2017-05-18 | 2019-01-01 | 瑞士商愛杜西亞製藥有限公司 | 嘧啶衍生物 |
MA49128A (fr) | 2017-05-18 | 2021-03-17 | Idorsia Pharmaceuticals Ltd | Dérivés de pyrimidine utilisés en tant que modulateurs des récepteurs des pge2 |
ES2893452T3 (es) | 2017-05-18 | 2022-02-09 | Idorsia Pharmaceuticals Ltd | Derivados de pirimidina como moduladores del receptor de PGE2 |
EA202091708A1 (ru) | 2018-01-17 | 2020-11-10 | Вертекс Фармасьютикалз Инкорпорейтед | Ингибиторы днк-пк |
BR112020013626A2 (pt) | 2018-01-17 | 2020-12-01 | Vertex Pharmaceuticals Incorporated | compostos de quinoxalinona, composições, métodos e kits para aumentar a eficiência de edição de genoma |
CN112300126A (zh) * | 2019-07-31 | 2021-02-02 | 山东轩竹医药科技有限公司 | 杂环类dna-pk抑制剂 |
CN112574179B (zh) * | 2019-09-29 | 2022-05-10 | 山东轩竹医药科技有限公司 | Dna-pk抑制剂 |
CN114478399A (zh) * | 2020-10-27 | 2022-05-13 | 华东理工大学 | 嘧菌酯低共熔混合物及其制备方法和应用 |
Family Cites Families (183)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5571506A (en) | 1989-08-14 | 1996-11-05 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aromatic oligomeric compounds useful as mimics of bioactive macromolecules |
CA2071897A1 (en) | 1989-12-28 | 1991-06-29 | Richard A. Glennon | Sigma receptor ligands and the use thereof |
US6004979A (en) | 1991-02-07 | 1999-12-21 | Hoechst Marion Roussel | Nitrogenous bicycles |
EP0498722B1 (fr) | 1991-02-07 | 1997-07-30 | Roussel Uclaf | Dérivés bicycliques azotés, leur procédé de préparation, les intermédiaires obtenus, leur application comme médicaments et les compositions pharmaceutiques les renfermant |
EP0519211A1 (de) | 1991-05-17 | 1992-12-23 | Hoechst Schering AgrEvo GmbH | Substituierte 4-Aminopyrimidine, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel |
DE4208254A1 (de) | 1992-03-14 | 1993-09-16 | Hoechst Ag | Substituierte pyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel und fungizid |
WO1993022291A1 (en) | 1992-04-24 | 1993-11-11 | E.I. Du Pont De Nemours And Company | Arthropodicidal and fungicidal aminopyrimidines |
US5595756A (en) | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
DE4437406A1 (de) | 1994-10-19 | 1996-04-25 | Hoechst Ag | Chinoxaline, Verfahren zu ihrer Herstellung und ihre Verwendung |
US5977117A (en) | 1996-01-05 | 1999-11-02 | Texas Biotechnology Corporation | Substituted phenyl compounds and derivatives thereof that modulate the activity of endothelin |
WO1998037079A1 (en) | 1997-02-19 | 1998-08-27 | Berlex Laboratories, Inc. | N-heterocyclic derivatives as nos inhibitors |
JPH10251255A (ja) | 1997-03-14 | 1998-09-22 | Nissan Chem Ind Ltd | アジン誘導体 |
SK158099A3 (en) | 1997-05-28 | 2000-06-12 | Rhone Poulenc Rorer Pharma | Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases |
DE19801598C2 (de) | 1998-01-17 | 2000-05-11 | Aventis Res & Tech Gmbh & Co | Katalytische Synthese von N-alkylierten Anilinen aus Olefinen und Anilinen |
DE19836697A1 (de) | 1998-08-13 | 2000-02-17 | Hoechst Marion Roussel De Gmbh | Substituierte 4-Amino-2-aryl-pyrimidine, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
WO2000042026A1 (en) | 1999-01-15 | 2000-07-20 | Novo Nordisk A/S | Non-peptide glp-1 agonists |
US6156373A (en) | 1999-05-03 | 2000-12-05 | Scimed Life Systems, Inc. | Medical device coating methods and devices |
US6258121B1 (en) | 1999-07-02 | 2001-07-10 | Scimed Life Systems, Inc. | Stent coating |
GB9924092D0 (en) | 1999-10-13 | 1999-12-15 | Zeneca Ltd | Pyrimidine derivatives |
US6552016B1 (en) | 1999-10-14 | 2003-04-22 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
AU2001234690A1 (en) | 2000-02-01 | 2001-08-14 | Cor Therapeutics, Inc. | 2-(1h)-quinolone and 2-(1h)-quinoxalone inhibitors of factor xa |
EP1259485B1 (en) | 2000-02-29 | 2005-11-30 | Millennium Pharmaceuticals, Inc. | BENZAMIDES AND RELATED INHIBITORS OF FACTOR Xa |
WO2001064646A2 (en) | 2000-03-01 | 2001-09-07 | Tularik Inc. | Hydrazones and analogs as cholesterol lowering agents |
DE10013318A1 (de) | 2000-03-17 | 2001-09-20 | Merck Patent Gmbh | Formulierung enthaltend Chinoxalinderivate |
US7419678B2 (en) | 2000-05-12 | 2008-09-02 | Cordis Corporation | Coated medical devices for the prevention and treatment of vascular disease |
US7498304B2 (en) | 2000-06-16 | 2009-03-03 | Curis, Inc. | Angiogenesis-modulating compositions and uses |
AU2001288432A1 (en) | 2000-09-01 | 2002-03-22 | Icos Corporation | Materials and methods to potentiate cancer treatment |
US7473691B2 (en) | 2000-09-15 | 2009-01-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
US6610677B2 (en) | 2000-09-15 | 2003-08-26 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
KR100876069B1 (ko) | 2000-09-15 | 2008-12-26 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나제 억제제로서 유용한 피라졸 화합물 및 이를 포함하는 약제학적 조성물 |
US6613776B2 (en) | 2000-09-15 | 2003-09-02 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
US6660731B2 (en) | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
US20040018228A1 (en) | 2000-11-06 | 2004-01-29 | Afmedica, Inc. | Compositions and methods for reducing scar tissue formation |
EP1343781B1 (en) | 2000-12-05 | 2008-09-03 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
MXPA03005610A (es) | 2000-12-21 | 2003-10-06 | Vertex Pharma | Compuestos de pirazol utiles como inhibidores de la proteina cinasa. |
US20040097502A1 (en) | 2001-02-02 | 2004-05-20 | Gellibert Francoise Jeanne | Pyrazoles as tgf inhibitors |
MY130778A (en) | 2001-02-09 | 2007-07-31 | Vertex Pharma | Heterocyclic inhibitiors of erk2 and uses thereof |
DE60223790D1 (de) | 2001-03-29 | 2008-01-10 | Vertex Pharma | Hemmer von c-jun-terminal kinase (jnk) und andere protein kinase |
ATE339416T1 (de) | 2001-04-13 | 2006-10-15 | Vertex Pharma | Inhibitoren von c-jun-n-terminalen-kinasen (jnk) und anderen proteinkinasen |
WO2002085909A1 (en) | 2001-04-20 | 2002-10-31 | Vertex Pharmaceuticals Incorporated | 9-deazaguanine derivatives as inhibitors of gsk-3 |
AU2002308748A1 (en) | 2001-05-16 | 2002-11-25 | Vertex Pharmaceuticals Incorporated | Heterocyclic substituted pyrazoles as inhibitors of src and other protein kinases |
MXPA03010961A (es) | 2001-05-31 | 2004-02-27 | Vertex Pharma | Compuestos de tiazol utiles como inhibidores de proteinas cinasas. |
DE60214703T2 (de) | 2001-06-01 | 2007-09-13 | Vertex Pharmaceuticals Inc., Cambridge | Thiazolverbindungen, die sich als inhibitoren von proteinkinasen eignen |
DE60232510D1 (de) | 2001-06-15 | 2009-07-16 | Vertex Pharma | 5-(2-aminopyrimidin-4-yl)benzisoxazole als proteinkinasehemmer |
CA2452603A1 (en) | 2001-07-03 | 2003-01-16 | Vertex Pharmaceuticals Incorporated | Isoxazolyl-pyrimidines as inhibitors of src and lck protein kinases |
US20030229390A1 (en) | 2001-09-17 | 2003-12-11 | Control Delivery Systems, Inc. | On-stent delivery of pyrimidines and purine analogs |
PL374315A1 (en) | 2001-10-25 | 2005-10-03 | Wisconsin Alumni Research Foundation | Vascular stent or graft coated or impregnated with protein tyrosine kinase inhibitors and method of using same |
US6939376B2 (en) | 2001-11-05 | 2005-09-06 | Sun Biomedical, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
DE60236322D1 (de) | 2001-12-07 | 2010-06-17 | Vertex Pharma | Verbindungen auf pyrimidin-basis als gsk-3-hemmer |
JP4656838B2 (ja) | 2002-02-06 | 2011-03-23 | バーテックス ファーマシューティカルズ インコーポレイテッド | Gsk−3の阻害剤として有用なヘテロアリール化合物 |
US20030199525A1 (en) | 2002-03-21 | 2003-10-23 | Hirst Gavin C. | Kinase inhibitors |
US20030207873A1 (en) | 2002-04-10 | 2003-11-06 | Edmund Harrington | Inhibitors of Src and other protein kinases |
AU2003237121A1 (en) | 2002-04-26 | 2003-11-10 | Vertex Pharmaceuticals Incorporated | Pyrrole derivatives as inhibitors of erk2 and uses thereof |
US20030204168A1 (en) | 2002-04-30 | 2003-10-30 | Gjalt Bosma | Coated vascular devices |
MXPA04011048A (es) | 2002-05-06 | 2005-02-17 | Vertex Pharmaceutivals Inc | Tiadiazol o oxasiazoles y su uso como inhibidores de proteina cinasa jak. |
AU2003231880A1 (en) | 2002-05-30 | 2003-12-19 | Vertex Pharmaceuticals Incorporated | Inhibitors of jak and cdk2 protein kinases |
US6835387B2 (en) | 2002-06-11 | 2004-12-28 | Scimed Life Systems, Inc. | Sustained release of superoxide dismutase mimics from implantable or insertable medical devices |
MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
US7361665B2 (en) | 2002-07-09 | 2008-04-22 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-Jun N-terminal kinases (JNK) and other protein kinases |
WO2004016597A2 (en) | 2002-08-14 | 2004-02-26 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors and uses thereof |
US7419984B2 (en) | 2002-10-17 | 2008-09-02 | Cell Therapeutics, Inc. | Pyrimidines and uses thereof |
ATE454378T1 (de) | 2002-11-01 | 2010-01-15 | Vertex Pharma | Verbindungen, die sich als inhibitoren vonjak und anderen proteinkinasen eignen |
CA2506773A1 (en) | 2002-11-04 | 2004-05-21 | Vertex Pharmaceuticals Incorporated | Heteroaryl-pyramidine derivatives as jak inhibitors |
WO2004058749A1 (en) | 2002-12-18 | 2004-07-15 | Vertex Pharmaceuticals Incorporated | Benzisoxazole derivatives useful as inhibitors of protein kinases |
US7144911B2 (en) | 2002-12-31 | 2006-12-05 | Deciphera Pharmaceuticals Llc | Anti-inflammatory medicaments |
EP1596869B1 (en) * | 2003-01-21 | 2014-06-04 | New Form Pharmaceuticals Inc. | Novel cocrystallization |
JP2006518381A (ja) | 2003-02-07 | 2006-08-10 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼのインヒビターとして有用なヘテロアリール置換ピロール |
JP4808154B2 (ja) | 2003-03-13 | 2011-11-02 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼインヒビターとして有用な組成物 |
EP1660473A2 (en) | 2003-03-24 | 2006-05-31 | Luitpold Pharmaceuticals, Inc. | Xanthones, thioxanthones and acridinones as dna-pk inhibitors |
WO2004087698A2 (en) | 2003-03-25 | 2004-10-14 | Vertex Pharmaceuticals Incorporated | Thiazoles useful as inhibitors of protein kinases |
US6875781B2 (en) | 2003-04-04 | 2005-04-05 | Cell Therapeutics, Inc. | Pyridines and uses thereof |
US7189724B2 (en) | 2003-04-15 | 2007-03-13 | Valeant Research And Development | Quinoxaline derivatives having antiviral activity |
WO2005026129A1 (en) | 2003-09-15 | 2005-03-24 | Gpc Biotech Ag | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
AU2004313928A1 (en) | 2003-12-02 | 2005-07-28 | Vertex Pharmaceuticals, Inc. | Heterocyclic protein kinase inhibitors and uses thereof |
CA2548172A1 (en) | 2003-12-04 | 2005-06-23 | Vertex Pharmaceuticals Incorporated | Quinoxalines useful as inhibitors of protein kinases |
TW200533357A (en) | 2004-01-08 | 2005-10-16 | Millennium Pharm Inc | 2-(amino-substituted)-4-aryl pyrimidines and related compounds useful for treating inflammatory diseases |
EP3053579A1 (en) | 2004-03-15 | 2016-08-10 | Sunesis Pharmaceuticals, Inc. | Use of sns-595 for treating ovarian cancer |
GB0405985D0 (en) | 2004-03-17 | 2004-04-21 | Novartis Forschungsstiftung | Kinase |
UA84929C2 (en) | 2004-05-14 | 2008-12-10 | Вертекс Фармасьютикалс Инкорпорейтед | Prodrugs of pyrrolylpyrimidine erk protein kinase inhibitors |
JP4449580B2 (ja) | 2004-05-31 | 2010-04-14 | 宇部興産株式会社 | 4−アラルキルアミノピリミジン誘導体及び抗菌剤 |
WO2005121121A2 (en) | 2004-06-04 | 2005-12-22 | Arena Pharmaceuticals, Inc. | Substituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
ZA200702645B (en) | 2004-09-17 | 2008-08-27 | Vertex Pharma | Diaminotriazole compounds useful as protein kinase inhibitors |
EP1815206B1 (en) | 2004-10-13 | 2016-04-06 | PTC Therapeutics, Inc. | Compounds for nonsense suppression, and methods for their use |
HN2005000795A (es) | 2004-10-15 | 2010-08-19 | Aventis Pharma Inc | Pirimidinas como antagonistas del receptor de prostaglandina d2 |
AU2005293384A1 (en) | 2004-10-15 | 2006-04-20 | Astrazeneca Ab | Quinoxalines as B Raf inhibitors |
US20060166936A1 (en) | 2004-10-29 | 2006-07-27 | Hayley Binch | Diaminotriazole compounds useful as inhibitors of protein kinases |
US7517870B2 (en) | 2004-12-03 | 2009-04-14 | Fondazione Telethon | Use of compounds that interfere with the hedgehog signaling pathway for the manufacture of a medicament for preventing, inhibiting, and/or reversing ocular diseases related with ocular neovascularization |
US20060142572A1 (en) | 2004-12-14 | 2006-06-29 | Gabriel Martinez-Botella | Inhibitors of ERK protein kinase and uses thereof |
US7501415B2 (en) | 2004-12-23 | 2009-03-10 | Vertex Pharmaceuticals Incorporated | Selective inhibitors of ERK protein kinase and uses thereof |
EP1850681B1 (en) | 2005-02-04 | 2019-12-18 | Firmenich Incorporated | Compounds comprising linked hetero aryl moieties and their use as novel umami flavor modifiers, tastants and taste enhancers for comestible compositions |
JP2008536835A (ja) | 2005-04-06 | 2008-09-11 | アイアールエム・リミテッド・ライアビリティ・カンパニー | ジアリールアミン含有化合物および組成物、ならびにステロイドホルモン核受容体のモジュレータとしてのそれらの使用 |
JP2008542219A (ja) | 2005-05-25 | 2008-11-27 | インゲニウム ファーマシューティカルズ ジーエムビーエイチ | 疼痛処置法 |
WO2006138418A2 (en) | 2005-06-14 | 2006-12-28 | President And Fellows Of Harvard College | Improvement of cognitive performance with sirtuin activators |
JP2007008045A (ja) | 2005-06-30 | 2007-01-18 | Mitsui Chemicals Inc | 光記録媒体および1h−キノキサリン−2−オン誘導体 |
EP1906967A4 (en) | 2005-07-26 | 2010-07-28 | Vertex Pharma | ABL Kinase Inhibition |
GB0520657D0 (en) | 2005-10-11 | 2005-11-16 | Ludwig Inst Cancer Res | Pharmaceutical compounds |
JP2009514875A (ja) | 2005-11-02 | 2009-04-09 | サイトキネティクス・インコーポレーテッド | 化学物質、組成物、および方法 |
EP1951715B1 (en) | 2005-11-03 | 2013-09-04 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
EP1951716B1 (en) | 2005-11-16 | 2011-05-04 | Vertex Pharmaceuticals, Inc. | Aminopyrimidines useful as kinase inhibitors |
WO2007082899A1 (en) | 2006-01-17 | 2007-07-26 | Vib Vzw | Inhibitors of prolyl-hydroxylase 1 for the treatment of skeletal muscle degeneration |
JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
UY30118A1 (es) | 2006-01-31 | 2007-06-29 | Tanabe Seiyaku Co | Compueto amina trisustituido |
WO2007109783A2 (en) | 2006-03-23 | 2007-09-27 | Janssen Pharmaceutica, N.V. | Substituted pyrimidine kinase inhibitors |
US20080280891A1 (en) | 2006-06-27 | 2008-11-13 | Locus Pharmaceuticals, Inc. | Anti-cancer agents and uses thereof |
WO2008008852A2 (en) | 2006-07-11 | 2008-01-17 | Emory University | Cxcr4 antagonists including heteroatoms for the treatment of medical disorders |
TW200811134A (en) | 2006-07-12 | 2008-03-01 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
PT2044056E (pt) | 2006-07-14 | 2012-12-05 | Novartis Ag | Derivados de pirimidina como inibidores de alk-5 |
US7635683B2 (en) | 2006-08-04 | 2009-12-22 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl tripeptide hepatitis C virus inhibitors |
EP2589597B1 (en) | 2006-08-22 | 2019-03-06 | Technion Research & Development Foundation | Heterocyclic derivatives binding to the peripheral-type benzodiazepine receptor (PBR) |
EP1903038A1 (de) | 2006-09-07 | 2008-03-26 | Bayer Schering Pharma Aktiengesellschaft | N-(1-Hetaryl-piperidin-4-yl)-(het)arylamide als EP2-Rezeptor Modulatoren |
US7875603B2 (en) | 2006-09-21 | 2011-01-25 | Nova Southeastern University | Specific inhibitors for vascular endothelial growth factor receptors |
WO2008042639A1 (en) * | 2006-10-02 | 2008-04-10 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
DE102006050512A1 (de) | 2006-10-26 | 2008-04-30 | Bayer Healthcare Ag | Substituierte heterocyclische Verbindungen und ihre Verwendung |
ATE457311T1 (de) | 2006-11-02 | 2010-02-15 | Vertex Pharma | Als inhibitoren von proteinkinasen geeignete aminopyridine und aminopyrimidine |
US20100234341A1 (en) | 2006-12-04 | 2010-09-16 | Marion Lanier | Substituted pyrimidines as adenosine receptor antagonists |
DE602007007985D1 (de) | 2006-12-19 | 2010-09-02 | Vertex Pharma | Als inhibitoren von proteinkinasen geeignete aminopyrimidine |
US20100098630A1 (en) | 2006-12-28 | 2010-04-22 | Ambrx, Inc. | Phenazine and Quinoxaline Substituted Amino Acids and Polypeptides |
WO2008092199A1 (en) | 2007-01-31 | 2008-08-07 | Cytopia Research Pty Ltd | Thiopyrimidine-based compounds and uses thereof |
WO2008106202A1 (en) | 2007-02-27 | 2008-09-04 | Housey Gerard M | Theramutein modulators |
MX2009009591A (es) | 2007-03-09 | 2009-11-10 | Vertex Pharma | Aminopirimidinas utiles como inhibidores de proteinas cinasas. |
ES2435997T3 (es) | 2007-03-09 | 2013-12-26 | Vertex Pharmaceuticals, Inc. | Aminopirimidinas útiles como inhibidores de las proteínas cinasas |
CA2679701A1 (en) | 2007-03-09 | 2008-09-18 | Vertex Pharmaceuticals Incorporated | Aminopyridines useful as inhibitors of protein kinases |
EP2142537A2 (en) | 2007-03-20 | 2010-01-13 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
DE102007015169A1 (de) | 2007-03-27 | 2008-10-02 | Universität des Saarlandes Campus Saarbrücken | 17Beta-Hydroxysteroid-Dehydrogenase-Typ1-Inhibitoren zur Behandlung hormonabhängiger Erkrankungen |
GB0706044D0 (en) | 2007-03-28 | 2007-05-09 | Syngenta Ltd | C0-Crystals |
WO2008128009A2 (en) | 2007-04-13 | 2008-10-23 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
US7910587B2 (en) | 2007-04-26 | 2011-03-22 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl dipeptide hepatitis C virus inhibitors |
WO2008137621A1 (en) | 2007-05-02 | 2008-11-13 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
JP5389785B2 (ja) | 2007-05-02 | 2014-01-15 | バーテックス ファーマシューティカルズ インコーポレイテッド | キナーゼ阻害剤として有用なチアゾールおよびピラゾール |
CA2688584A1 (en) | 2007-05-02 | 2008-11-13 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
JP2010526823A (ja) | 2007-05-10 | 2010-08-05 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | Pi3キナーゼ阻害物質としてのキノキサリン誘導体 |
WO2008144253A1 (en) | 2007-05-14 | 2008-11-27 | Irm Llc | Protein kinase inhibitors and methods for using thereof |
EP2164842A2 (en) | 2007-05-24 | 2010-03-24 | Vertex Pharmaceuticals Incorporated | Thiazoles and pyrazoles useful as kinase inhibitors |
TWI443090B (zh) | 2007-05-25 | 2014-07-01 | Abbvie Deutschland | 作為代謝性麩胺酸受體2(mglu2 受體)之正向調節劑之雜環化合物 |
WO2009004621A1 (en) | 2007-07-02 | 2009-01-08 | Technion Research & Development Foundation Ltd. | Compositions, articles and methods comprising tspo ligands for preventing or reducing tobacco-associated damage |
EP2170338A2 (en) | 2007-07-06 | 2010-04-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Dna-pkcs modulates energy regulation and brain function |
NZ582426A (en) | 2007-08-01 | 2011-04-29 | Kumiai Chemical Industry Co | Oxopyrazine derivative and herbicide |
WO2009042294A2 (en) | 2007-08-10 | 2009-04-02 | Burnham Institute For Medical Research | Tissue-nonspecific alkaline phosphatase (tnap) activators and uses thereof |
DE102007044032A1 (de) | 2007-09-14 | 2009-03-19 | Bayer Healthcare Ag | Substituierte heterocyclische Verbindungen und ihre Verwendung |
KR20100090772A (ko) | 2007-10-12 | 2010-08-17 | 인게니움 파르마코이티칼스 게엠베하 | 단백질 키나제 억제제 |
BRPI0817135A2 (pt) | 2007-11-06 | 2014-10-07 | Du Pont | Composto, método de controle de doenças de plantas e composições fungicidas |
EP2231624A4 (en) | 2007-12-21 | 2011-07-06 | Progenics Pharm Inc | TRIAZINE AND CORRESPONDING COMPOUNDS WITH ANTIVIRAL EFFECT, COMPOSITIONS AND METHOD THEREFOR |
US8598202B2 (en) | 2008-02-19 | 2013-12-03 | Janssen Pharmaceutica Nv | Aryl-hydroxyethylamino-pyrimidines and triazines as modulators of fatty acid amide hydrolase |
US20110009421A1 (en) | 2008-02-27 | 2011-01-13 | Takeda Pharmaceutical Company Limited | Compound having 6-membered aromatic ring |
JP5618837B2 (ja) | 2008-03-05 | 2014-11-05 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | インスリン分泌刺激剤としてのキノキサリノン誘導体、それらを得る方法および糖尿病を治療するためのそれらの使用 |
US8268834B2 (en) | 2008-03-19 | 2012-09-18 | Novartis Ag | Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme |
US20110065739A1 (en) | 2008-06-02 | 2011-03-17 | Makoto Ishikawa | Novel isoxazole drivative |
EP2285786B1 (en) | 2008-06-16 | 2013-10-09 | Merck Patent GmbH | Quinoxalinedione derivatives |
EP2138488A1 (en) | 2008-06-26 | 2009-12-30 | sanofi-aventis | 4-(pyridin-4-yl)-1H-[1,3,5]triazin-2-one derivatives as GSK3-beta inhibitors for the treatment of neurodegenerative diseases |
CA2731451A1 (en) | 2008-07-23 | 2010-01-28 | Vertex Pharmaceuticals Incorporated | Pyrazolopyridine kinase inhibitors |
WO2010048149A2 (en) | 2008-10-20 | 2010-04-29 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
AR074199A1 (es) | 2008-11-20 | 2010-12-29 | Glaxosmithkline Llc | Compuesto de 6-(4-pirimidinil)-1h-indazol, composiciones farmaceuticas que lo comprenden y su uso para preparar un medicamento util para el tratamiento o disminucion de la gravedad del cancer. |
WO2010065899A2 (en) | 2008-12-05 | 2010-06-10 | Molecular Insight Pharmaceuticals, Inc. | Technetium-and rhenium-bis(heteroaryl)complexes and methods of use thereof |
CA3013000C (en) | 2008-12-19 | 2022-12-13 | Vertex Pharmaceuticals Incorporated | Pyrazine derivatives useful as inhibitors of atr kinase |
EP2396004A4 (en) | 2009-02-11 | 2012-07-25 | Reaction Biology Corp | SELECTIVE KINASE HEMMER |
JP2010111702A (ja) | 2009-02-16 | 2010-05-20 | Tetsuya Nishio | 複素環化合物、その製造法および用途 |
AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
WO2011022348A1 (en) | 2009-08-18 | 2011-02-24 | Janssen Pharmaceutica Nv | Ethylene diamine modulators of fatty acid amide hydrolase |
AR077999A1 (es) | 2009-09-02 | 2011-10-05 | Vifor Int Ag | Antagonistas de pirimidin y triazin-hepcidina |
US9062076B2 (en) | 2009-10-22 | 2015-06-23 | Fibrotech Therapeutics Pty Ltd | Fused ring analogues of anti-fibrotic agents |
ES2360333B1 (es) | 2009-10-29 | 2012-05-04 | Consejo Superior De Investigaciones Cientificas (Csic) (70%) | Derivados de bis (aralquil) amino y sistemas (hetero) aromaticos de seis miembros y su uso en el tratamiento de patologias neurodegenerativas, incluida la enfermedad de alzheimer |
JPWO2011052756A1 (ja) | 2009-10-30 | 2013-03-21 | 持田製薬株式会社 | 新規3−ヒドロキシ−5−アリールイソキサゾール誘導体 |
NZ601408A (en) | 2009-12-25 | 2013-12-20 | Mochida Pharm Co Ltd | Novel 3-hydroxy-5-arylisothiazole derivative |
UY33213A (es) | 2010-02-18 | 2011-09-30 | Almirall Sa | Derivados de pirazol como inhibidores de jak |
SG183855A1 (en) | 2010-03-16 | 2012-10-30 | Merck Patent Gmbh | Morpholinylquinazolines |
TWI516264B (zh) | 2010-05-06 | 2016-01-11 | 臺北醫學大學 | 芳香醯喹啉化合物 |
JP2011246389A (ja) | 2010-05-26 | 2011-12-08 | Oncotherapy Science Ltd | Ttk阻害作用を有する縮環ピラゾール誘導体 |
DE102010025786A1 (de) | 2010-07-01 | 2012-01-05 | Merck Patent Gmbh | Pyrazolochinoline |
DE102010035744A1 (de) | 2010-08-28 | 2012-03-01 | Merck Patent Gmbh | Imidazolonylchinoline |
WO2012129562A2 (en) | 2011-03-24 | 2012-09-27 | The Scripps Research Institute | Compounds and methods for inducing chondrogenesis |
JP2014510151A (ja) | 2011-04-05 | 2014-04-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Atrキナーゼ(trakinase)阻害剤として有用なアミノピラジン化合物 |
GB201114051D0 (en) | 2011-08-15 | 2011-09-28 | Domainex Ltd | Compounds and their uses |
CN104053442B (zh) | 2011-08-26 | 2017-06-23 | 润新生物公司 | 某些化学实体、组合物及方法 |
JP6093768B2 (ja) | 2011-09-14 | 2017-03-08 | ニューファーマ, インコーポレイテッド | 特定の化学的実体、組成物、および方法 |
WO2013043935A1 (en) | 2011-09-21 | 2013-03-28 | Neupharma, Inc. | Certain chemical entites, compositions, and methods |
WO2013049701A1 (en) | 2011-09-30 | 2013-04-04 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
DE102011118830A1 (de) | 2011-11-18 | 2013-05-23 | Merck Patent Gmbh | Morpholinylbenzotriazine |
GB201120993D0 (en) | 2011-12-06 | 2012-01-18 | Imp Innovations Ltd | Novel compounds and their use in therapy |
WO2013112950A2 (en) | 2012-01-25 | 2013-08-01 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
PT2841428T (pt) * | 2012-04-24 | 2018-11-29 | Vertex Pharma | Inibidores de adn-pk |
EP2916838B1 (en) | 2012-11-12 | 2019-03-13 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
EP3985003B1 (en) | 2013-03-12 | 2023-08-09 | Vertex Pharmaceuticals Incorporated | Dna-pk inhibitors |
CN105814036B (zh) * | 2013-10-17 | 2018-10-26 | 沃泰克斯药物股份有限公司 | 作为dna-pk抑制剂的共晶 |
-
2014
- 2014-10-17 CN CN201480067896.3A patent/CN105814036B/zh active Active
- 2014-10-17 RS RS20181387A patent/RS57969B1/sr unknown
- 2014-10-17 PT PT14799578T patent/PT3057953T/pt unknown
- 2014-10-17 CA CA2927631A patent/CA2927631C/en active Active
- 2014-10-17 LT LTEP18188034.5T patent/LT3424920T/lt unknown
- 2014-10-17 PT PT181880345T patent/PT3424920T/pt unknown
- 2014-10-17 PE PE2016000512A patent/PE20161022A1/es unknown
- 2014-10-17 RU RU2018143803A patent/RU2018143803A/ru unknown
- 2014-10-17 RS RS20200607A patent/RS60426B1/sr unknown
- 2014-10-17 SI SI201431595T patent/SI3424920T1/sl unknown
- 2014-10-17 CN CN201811084734.7A patent/CN108771681B/zh active Active
- 2014-10-17 MX MX2016004992A patent/MX361488B/es active IP Right Grant
- 2014-10-17 EP EP14799578.1A patent/EP3057953B1/en active Active
- 2014-10-17 PL PL18188034T patent/PL3424920T3/pl unknown
- 2014-10-17 BR BR112016008452-7A patent/BR112016008452B1/pt active IP Right Grant
- 2014-10-17 PL PL14799578T patent/PL3057953T3/pl unknown
- 2014-10-17 KR KR1020167012891A patent/KR102411227B1/ko active IP Right Grant
- 2014-10-17 DK DK14799578.1T patent/DK3057953T3/en active
- 2014-10-17 SI SI201430963T patent/SI3057953T1/sl unknown
- 2014-10-17 AU AU2014337154A patent/AU2014337154B2/en active Active
- 2014-10-17 UA UAA201605244A patent/UA120915C2/uk unknown
- 2014-10-17 RU RU2016118771A patent/RU2675270C2/ru active
- 2014-10-17 LT LTEP14799578.1T patent/LT3057953T/lt unknown
- 2014-10-17 ES ES18188034T patent/ES2802296T3/es active Active
- 2014-10-17 SG SG11201602962PA patent/SG11201602962PA/en unknown
- 2014-10-17 HU HUE14799578A patent/HUE041877T2/hu unknown
- 2014-10-17 JP JP2016524021A patent/JP6408569B2/ja active Active
- 2014-10-17 WO PCT/US2014/061102 patent/WO2015058067A1/en active Application Filing
- 2014-10-17 DK DK18188034.5T patent/DK3424920T3/da active
- 2014-10-17 HU HUE18188034A patent/HUE051275T2/hu unknown
- 2014-10-17 EP EP18188034.5A patent/EP3424920B1/en active Active
- 2014-10-17 ES ES14799578T patent/ES2705342T3/es active Active
-
2016
- 2016-04-14 IL IL24511716A patent/IL245117B/en active IP Right Grant
- 2016-04-15 US US15/130,266 patent/US10039761B2/en active Active
- 2016-04-15 CL CL2016000916A patent/CL2016000916A1/es unknown
- 2016-04-21 ZA ZA2016/02777A patent/ZA201602777B/en unknown
-
2018
- 2018-07-18 US US16/038,696 patent/US10716789B2/en active Active
- 2018-08-13 JP JP2018152292A patent/JP6763919B2/ja active Active
- 2018-08-15 AU AU2018217249A patent/AU2018217249A1/en not_active Abandoned
- 2018-11-05 HR HRP20181841TT patent/HRP20181841T1/hr unknown
-
2020
- 2020-06-26 HR HRP20201011TT patent/HRP20201011T1/hr unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2016118771A (ru) | Со-кристаллы и содержащие их фармацевтические композиции | |
JP2016533370A5 (ru) | ||
Trask et al. | Achieving polymorphic and stoichiometric diversity in cocrystal formation: Importance of solid-state grinding, powder X-ray structure determination, and seeding | |
Sanphui et al. | Pharmaceutical cocrystals of niclosamide | |
Khan et al. | Crystal engineering of pharmaceutical co-crystals: application of methyl paraben as molecular hook | |
Mittapalli et al. | Soluble salts and cocrystals of clotrimazole | |
Grifasi et al. | Using salt cocrystals to improve the solubility of niclosamide | |
Pranzo et al. | Enantiotropically related albendazole polymorphs | |
Lusi et al. | Expanding the scope of molecular mixed crystals enabled by three component solid solutions | |
Braga et al. | Molecular salts of anesthetic lidocaine with dicarboxylic acids: solid-state properties and a combined structural and spectroscopic study | |
Golob et al. | Improving biopharmaceutical properties of vinpocetine through cocrystallization | |
Zheng et al. | Structures of polymorphic agomelatine and its cocrystals with acetic acid and ethylene glycol | |
Arenas-Garcia et al. | Modification of the supramolecular hydrogen-bonding patterns of acetazolamide in the presence of different cocrystal formers: 3: 1, 2: 1, 1: 1, and 1: 2 cocrystals from screening with the structural isomers of hydroxybenzoic acids, aminobenzoic acids, hydroxybenzamides, aminobenzamides, nicotinic acids, nicotinamides, and 2, 3-dihydroxybenzoic acids | |
Goud et al. | Solubility and stability advantage of aceclofenac salts | |
CN1997621A (zh) | (-)-(1r,2r)-3-(3-二甲基氨基-1-乙基-2-甲基丙基)-苯酚盐酸盐的晶形 | |
Mayer et al. | 17O NMR and density functional theory study of the dynamics of the carboxylate groups in DOTA complexes of lanthanides in aqueous solution | |
RU2013158816A (ru) | Новые сокристаллы агомелатина, способ их получения и фармацевтические композиции, которые их содержат | |
Allu et al. | Supramolecular synthons in bumetanide cocrystals and ternary products | |
Lai et al. | Tunable Keplerate Type‐Cluster “Mo132” Cavity with Dicarboxylate Anions | |
Hariprasad et al. | Cocrystals of ethenzamide: study of structural and physicochemical properties | |
CN107848991A (zh) | (z)‑4‑(5‑((3‑苄基‑4‑氧代‑2‑硫代噻唑烷‑5‑亚基)甲基)呋喃‑2‑基)苯甲酸的固体形式 | |
Bruni et al. | Multicomponent crystals of gliclazide and tromethamine: preparation, physico-chemical, and pharmaceutical characterization | |
CN105218484A (zh) | 酒石酸卡利拉嗪及其制备方法和医药用途 | |
CN107629010B (zh) | 一种吡嗪酰胺与槲皮素的共晶及其制备方法 | |
Zhang et al. | The luminescent behaviors based on Ambroxol: syntheses, crystal structure and Hirshfeld surface analysis |