RU2564527C2 - Производное фталазинонкетона, способ его получения и его фармацевтическое применение - Google Patents
Производное фталазинонкетона, способ его получения и его фармацевтическое применение Download PDFInfo
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- RU2564527C2 RU2564527C2 RU2013106754/04A RU2013106754A RU2564527C2 RU 2564527 C2 RU2564527 C2 RU 2564527C2 RU 2013106754/04 A RU2013106754/04 A RU 2013106754/04A RU 2013106754 A RU2013106754 A RU 2013106754A RU 2564527 C2 RU2564527 C2 RU 2564527C2
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- RU
- Russia
- Prior art keywords
- pyrazine
- trifluoromethyl
- mmol
- group
- methyl
- Prior art date
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- -1 Phthalazine ketone Chemical class 0.000 title abstract description 90
- 238000000034 method Methods 0.000 title abstract description 18
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 title abstract 2
- 239000003814 drug Substances 0.000 claims abstract description 26
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims abstract description 23
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 claims abstract description 22
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 239000003112 inhibitor Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 91
- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 125000000623 heterocyclic group Chemical group 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 36
- 206010028980 Neoplasm Diseases 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 201000011510 cancer Diseases 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 229940079593 drug Drugs 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 206010006187 Breast cancer Diseases 0.000 claims description 12
- 208000026310 Breast neoplasm Diseases 0.000 claims description 12
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 12
- 229960004964 temozolomide Drugs 0.000 claims description 12
- 210000004881 tumor cell Anatomy 0.000 claims description 12
- 206010009944 Colon cancer Diseases 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- 238000002512 chemotherapy Methods 0.000 claims description 6
- 208000029742 colonic neoplasm Diseases 0.000 claims description 6
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 230000005865 ionizing radiation Effects 0.000 claims description 5
- 201000007270 liver cancer Diseases 0.000 claims description 5
- 208000014018 liver neoplasm Diseases 0.000 claims description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 201000002528 pancreatic cancer Diseases 0.000 claims description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000035945 sensitivity Effects 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 18
- 239000000126 substance Substances 0.000 abstract description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 87
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- 230000002829 reductive effect Effects 0.000 description 78
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 54
- 238000003756 stirring Methods 0.000 description 54
- 238000004949 mass spectrometry Methods 0.000 description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000007787 solid Substances 0.000 description 48
- 125000000753 cycloalkyl group Chemical group 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000000706 filtrate Substances 0.000 description 34
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- 125000001072 heteroaryl group Chemical group 0.000 description 33
- 125000003118 aryl group Chemical group 0.000 description 32
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- 238000010828 elution Methods 0.000 description 29
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- PAXLJNGPFJEKQX-UHFFFAOYSA-N 2-fluoro-5-[(4-oxo-3h-phthalazin-1-yl)methyl]benzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=C1 PAXLJNGPFJEKQX-UHFFFAOYSA-N 0.000 description 22
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 12
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- 231100000277 DNA damage Toxicity 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 125000005343 heterocyclic alkyl group Chemical group 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 125000003367 polycyclic group Chemical group 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000012661 PARP inhibitor Substances 0.000 description 10
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 description 10
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 10
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 125000000304 alkynyl group Chemical group 0.000 description 10
- 125000006413 ring segment Chemical group 0.000 description 10
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 125000003282 alkyl amino group Chemical group 0.000 description 8
- 125000005366 cycloalkylthio group Chemical group 0.000 description 8
- YARSFSWHQVBNGV-UHFFFAOYSA-N methyl 3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxylate Chemical compound C1CNCC2=C(C(=O)OC)N=C(C(F)(F)F)N21 YARSFSWHQVBNGV-UHFFFAOYSA-N 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000012047 saturated solution Substances 0.000 description 8
- 150000003573 thiols Chemical class 0.000 description 8
- 0 *c1ccc(CC(C2C=CC=CC22)=NNC2=O)cc1C(N1Cc2ccc[n]2CC1)=O Chemical compound *c1ccc(CC(C2C=CC=CC22)=NNC2=O)cc1C(N1Cc2ccc[n]2CC1)=O 0.000 description 7
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- 241000699670 Mus sp. Species 0.000 description 6
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- OWUJPAWZSIXQKU-UHFFFAOYSA-N 4-[[4-fluoro-3-[1-(hydroxymethyl)-3-(trifluoromethyl)-6,8-dihydro-5h-imidazo[1,5-a]pyrazine-7-carbonyl]phenyl]methyl]-2h-phthalazin-1-one Chemical compound C1=CC=C2C(CC=3C=C(C(=CC=3)F)C(=O)N3CCN4C(=NC(=C4C3)CO)C(F)(F)F)=NNC(=O)C2=C1 OWUJPAWZSIXQKU-UHFFFAOYSA-N 0.000 description 5
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
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- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 4
- IYQUOZXROLJXSS-UHFFFAOYSA-N 3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide Chemical compound C1CNCC2=C(C(=O)N)N=C(C(F)(F)F)N21 IYQUOZXROLJXSS-UHFFFAOYSA-N 0.000 description 4
- JPYXQNYTOSHIAC-UHFFFAOYSA-N 4-[[3-(3,4-dihydro-1h-pyrrolo[1,2-a]pyrazine-2-carbonyl)-4-fluorophenyl]methyl]-2h-phthalazin-1-one Chemical compound C1CN2C=CC=C2CN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F JPYXQNYTOSHIAC-UHFFFAOYSA-N 0.000 description 4
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- HFYKJMSAJNKYCB-UHFFFAOYSA-N 4-[[4-fluoro-3-[1-(morpholine-4-carbonyl)-3-(trifluoromethyl)-6,8-dihydro-5h-imidazo[1,5-a]pyrazine-7-carbonyl]phenyl]methyl]-2h-phthalazin-1-one Chemical compound FC1=CC=C(CC=2C3=CC=CC=C3C(=O)NN=2)C=C1C(=O)N(C1)CCN(C(=N2)C(F)(F)F)C1=C2C(=O)N1CCOCC1 HFYKJMSAJNKYCB-UHFFFAOYSA-N 0.000 description 4
- UETNQARZLQIKEB-UHFFFAOYSA-N 4-[[4-fluoro-3-[3-(2,2,2-trifluoroethyl)-6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2h-phthalazin-1-one Chemical compound C1CN2C(CC(F)(F)F)=NN=C2CN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F UETNQARZLQIKEB-UHFFFAOYSA-N 0.000 description 4
- QERWDUVWGUUQKN-UHFFFAOYSA-N 7-[2-fluoro-5-[(4-oxo-3h-phthalazin-1-yl)methyl]benzoyl]-3-(trifluoromethyl)-6,8-dihydro-5h-imidazo[1,5-a]pyrazine-1-carbonitrile Chemical compound C1CN2C(C(F)(F)F)=NC(C#N)=C2CN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F QERWDUVWGUUQKN-UHFFFAOYSA-N 0.000 description 4
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
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- HIIJWJUIQSSMSB-UHFFFAOYSA-N methyl 7-[2-fluoro-5-[(4-oxo-3h-phthalazin-1-yl)methyl]benzoyl]-3-(trifluoromethyl)-6,8-dihydro-5h-imidazo[1,5-a]pyrazine-1-carboxylate Chemical compound C1=CC=C2C(CC=3C=C(C(=CC=3)F)C(=O)N3CCN4C(=NC(=C4C3)C(=O)OC)C(F)(F)F)=NNC(=O)C2=C1 HIIJWJUIQSSMSB-UHFFFAOYSA-N 0.000 description 4
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- JXHBMURNQNBDSX-UHFFFAOYSA-N n-methyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide Chemical compound C1CNCC2=C(C(=O)NC)N=C(C(F)(F)F)N21 JXHBMURNQNBDSX-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—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
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
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- A—HUMAN NECESSITIES
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- 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
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- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
- C07D403/02—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 two hetero rings
- C07D403/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
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- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| CN201010248307.5 | 2010-08-09 | ||
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| PCT/CN2011/001223 WO2012019427A1 (zh) | 2010-08-09 | 2011-07-26 | 酞嗪酮类衍生物、其制备方法及其在医药上的应用 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2777519C2 (ru) * | 2017-12-06 | 2022-08-05 | Цзянсу Хэнжуй Медицин Ко., Лтд. | Применение ингибитора parp в лечении резистентного к химиотерапии рака яичников или рака молочной железы |
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| CN102898377B (zh) * | 2012-02-14 | 2016-01-20 | 南京圣和药业股份有限公司 | 一类酞嗪酮衍生物及其用途 |
| CN102702108A (zh) * | 2012-06-27 | 2012-10-03 | 上海大学 | 1,2-二氢酞嗪类化合物及其合成方法 |
| CN103570725B (zh) * | 2012-08-01 | 2017-03-22 | 中国科学院上海药物研究所 | 哌嗪并三唑类化合物及其制备方法和用途 |
| CN102863393A (zh) * | 2012-09-26 | 2013-01-09 | 上海大学 | 1,2-二氢酞嗪类化合物及其合成方法 |
| WO2014102817A1 (en) | 2012-12-31 | 2014-07-03 | Cadila Healthcare Limited | Substituted phthalazin-1 (2h)-one derivatives as selective inhibitors of poly (adp-ribose) polymerase-1 |
| KR101670126B1 (ko) | 2013-09-13 | 2016-10-27 | 일동제약(주) | 신규 프탈라지논 유도체 및 그 제조방법 |
| UY35834A (es) | 2013-11-14 | 2015-05-29 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Piperazinas de pirazolo sustituido como inhibidores de caseína quinasa 1 delta y epsilon |
| ES2879434T3 (es) | 2015-07-23 | 2021-11-22 | Inst Curie | Uso de una combinación de molécula Dbait e inhibidores de PARP para tratamiento del cáncer |
| RU2750151C2 (ru) | 2015-11-20 | 2021-06-22 | Форма Терапьютикс, Инк. | Гипоксантины в качестве ингибиторов убиквитин-специфической протеазы 1 |
| CN106749261A (zh) * | 2015-11-23 | 2017-05-31 | 中国科学院上海药物研究所 | 一类取代三唑并哌嗪类parp抑制剂及其制备方法和用途 |
| WO2017101796A1 (zh) * | 2015-12-16 | 2017-06-22 | 四川科伦博泰生物医药股份有限公司 | 酞嗪酮衍生物、其制备方法及用途 |
| WO2017156350A1 (en) | 2016-03-09 | 2017-09-14 | K-Gen, Inc. | Methods of cancer treatment |
| TWI771344B (zh) * | 2016-12-01 | 2022-07-21 | 大陸商江蘇恆瑞醫藥股份有限公司 | 一種ｖｅｇｆｒ抑制劑與ｐａｒｐ抑制劑聯合在製備治療胃癌的藥物中的用途 |
| WO2018162439A1 (en) | 2017-03-08 | 2018-09-13 | Onxeo | New predictive biomarker for the sensitivity to a treatment of cancer with a dbait molecule |
| PT3448859T (pt) | 2017-03-20 | 2019-10-25 | Forma Therapeutics Inc | Composições de pirrolopirrole como ativadores de piruvato quinase (pkr). |
| CN110475779A (zh) | 2017-04-12 | 2019-11-19 | 豪夫迈·罗氏有限公司 | 标记含醛靶分子的方法 |
| MX2020002046A (es) * | 2017-08-24 | 2020-09-17 | Jiangsu Hengrui Medicine Co | Forma cristalina del inhibidor de parp-1 y método de preparación de ésta. |
| BR112020010435A2 (pt) * | 2017-12-06 | 2020-11-24 | Jiangsu Hengrui Medicine Co., Ltd. | uso de inibidor da parp no tratamento de câncer de ovário ou câncer de mama resistente à quimioterapia |
| WO2019137358A1 (zh) | 2018-01-09 | 2019-07-18 | 江苏恒瑞医药股份有限公司 | 一种parp抑制剂及其中间体的制备方法 |
| AU2019212093B2 (en) | 2018-01-26 | 2024-05-30 | Recordati Industria Chimica E Farmaceutica S.P.A | Triazole, imidazole and pyrrole condensed piperazine derivatives and their use as modulators of mGlu5 receptors |
| WO2019169156A1 (en) * | 2018-02-28 | 2019-09-06 | The Trustees Of The University Of Pennsylvania | Low affinity poly(ad-ribose) polymerase 1 dependent cytotoxic agents |
| US20200407720A1 (en) | 2018-03-13 | 2020-12-31 | Onxeo | A dbait molecule against acquired resistance in the treatment of cancer |
| BR112020019824A2 (pt) * | 2018-03-29 | 2021-01-05 | Board Of Regents, The University Of Texas System | Composto de fórmula estrutural i ou um sal do mesmo, composição farmacêutica, método de inibição de cbp, método de inibição de p300, método de tratamento de uma doença mediada por cbp, método de tratamento de uma doença mediada por p300 e método para alcançar um efeito em um paciente |
| US12053458B2 (en) | 2018-09-19 | 2024-08-06 | Novo Nordisk Health Care Ag | Treating sickle cell disease with a pyruvate kinase R activating compound |
| ES2989438T3 (es) | 2018-09-19 | 2024-11-26 | Novo Nordisk Healthcare Ag | Activación de la piruvato cinasa R |
| CN112584836A (zh) * | 2018-10-22 | 2021-03-30 | 江苏恒瑞医药股份有限公司 | 一种ar拮抗剂联合parp抑制剂在制备治疗前列腺癌的药物中的用途 |
| KR102912737B1 (ko) * | 2018-11-16 | 2026-01-15 | 지앙수 헨그루이 파마슈티컬스 컴퍼니 리미티드 | Parp 억제제를 포함하는 약학 조성물 |
| TW202110448A (zh) * | 2019-05-28 | 2021-03-16 | 大陸商江蘇恆瑞醫藥股份有限公司 | Ｐａｒｐ抑制劑聯合ｖｅｇｆｒ抑制劑用於治療卵巢癌或乳腺癌的用途 |
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| CN112870365A (zh) * | 2019-11-29 | 2021-06-01 | 江苏恒瑞医药股份有限公司 | Ezh2抑制剂和/或parp抑制剂与化疗药物联合在制备治疗肿瘤药物中的用途 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| CA3176219A1 (en) | 2020-04-21 | 2021-10-28 | Kunhee LEE | Crystalline forms of phthalazinone compound |
| JP7626783B2 (ja) | 2020-04-21 | 2025-02-07 | アイディーエンス カンパニー リミテッド | フタラジノン誘導体及びその中間体を調製するプロセス |
| CN111732594B (zh) * | 2020-08-18 | 2022-03-04 | 苏州富士莱医药股份有限公司 | 一种氟唑帕利的制备方法 |
| EP4221708A4 (en) | 2020-10-02 | 2024-11-06 | Board of Regents, The University of Texas System | IMIDAZOPIPERAZINE INHIBITORS OF TRANSCRIPTION-ACTIVATING PROTEINS |
| AU2021355480B2 (en) | 2020-10-02 | 2026-03-05 | Board Of Regents, The University Of Texas System | Imidazopiperazine inhibitors of transcription activating proteins |
| US12059419B2 (en) | 2020-10-16 | 2024-08-13 | Idience Co., Ltd. | Pharmaceutical composition comprising phthalazinone derivatives |
| US12128035B2 (en) | 2021-03-19 | 2024-10-29 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
| EP4349836A4 (en) * | 2021-05-24 | 2024-10-30 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | NITROGEN-CONTAINING HETEROCYCLIC COMPOUND, ITS PREPARATION METHOD AND ITS APPLICATION IN DRUGS |
| US20240317762A1 (en) * | 2021-07-16 | 2024-09-26 | Oregon Health & Science University | Phthalazinone-based parp-1 inhibitors |
| CA3226796A1 (en) * | 2021-07-29 | 2023-02-02 | Xiaoxia Yan | Novel parp7 inhibitor and use thereof |
| CN115650988B (zh) * | 2022-10-27 | 2024-09-13 | 江苏恒瑞医药股份有限公司 | 一种parp抑制剂的制备方法 |
| WO2024109871A1 (zh) * | 2022-11-23 | 2024-05-30 | 江苏恒瑞医药股份有限公司 | 一种含氮杂环类化合物的可药用盐、晶型及制备方法 |
| WO2024188265A1 (zh) * | 2023-03-13 | 2024-09-19 | 江苏豪森药业集团有限公司 | 哌啶烯类化合物在制备治疗癌症的药物中的应用 |
| CN121398822A (zh) | 2023-06-21 | 2026-01-23 | 四方生物科学有限公司 | 用于在治疗hr功能正常的癌症的方法中的用途的包含脱氧胞苷衍生物和parp抑制剂的组合 |
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2011
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- 2011-07-26 WO PCT/CN2011/001223 patent/WO2012019427A1/zh not_active Ceased
- 2011-07-26 AU AU2011288876A patent/AU2011288876B2/en active Active
- 2011-07-26 UA UAA201301524A patent/UA111161C2/uk unknown
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- 2011-07-26 PT PT118159862T patent/PT2604610T/pt unknown
- 2011-07-26 US US13/811,957 patent/US9273052B2/en active Active
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- 2011-07-26 ES ES11815986.2T patent/ES2582315T3/es active Active
- 2011-07-26 CA CA2806324A patent/CA2806324C/en active Active
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- 2011-07-26 PL PL11815986.2T patent/PL2604610T3/pl unknown
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2016
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| RU2292337C2 (ru) * | 2002-02-19 | 2007-01-27 | Оно Фармасьютикал Ко., Лтд. | Конденсированные производные пиридазина и лекарственные препараты, содержащие данные соединения в качестве активного ингредиента |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2792620C2 (ru) * | 2017-08-24 | 2023-03-22 | Цзянсу Хэнжуй Медисин Ко., Лтд. | Кристаллическая форма ингибитора parp-1 и способ ее получения |
| RU2777519C2 (ru) * | 2017-12-06 | 2022-08-05 | Цзянсу Хэнжуй Медицин Ко., Лтд. | Применение ингибитора parp в лечении резистентного к химиотерапии рака яичников или рака молочной железы |
| RU2777597C2 (ru) * | 2018-01-09 | 2022-08-08 | Цзянсу Хэнжуй Медисин Ко., Лтд. | Способ получения ингибитора parp и его промежуточного соединения |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2604610A4 (en) | 2013-12-25 |
| JP5808408B2 (ja) | 2015-11-10 |
| EP2604610A1 (en) | 2013-06-19 |
| CA2806324A1 (en) | 2012-02-16 |
| KR20130110149A (ko) | 2013-10-08 |
| CN102686591B (zh) | 2014-03-19 |
| BR112013002220B1 (pt) | 2021-09-21 |
| US9273052B2 (en) | 2016-03-01 |
| PT2604610T (pt) | 2016-07-13 |
| WO2012019427A1 (zh) | 2012-02-16 |
| HK1174030A1 (en) | 2013-05-31 |
| AU2011288876A2 (en) | 2013-02-21 |
| US20160151367A1 (en) | 2016-06-02 |
| US9566277B2 (en) | 2017-02-14 |
| CN102686591A (zh) | 2012-09-19 |
| AU2011288876B2 (en) | 2014-08-21 |
| JP2013535491A (ja) | 2013-09-12 |
| ES2582315T3 (es) | 2016-09-12 |
| RU2013106754A (ru) | 2014-09-20 |
| US20130131068A1 (en) | 2013-05-23 |
| HUE029275T2 (en) | 2017-02-28 |
| EP2604610B1 (en) | 2016-05-11 |
| UA111161C2 (uk) | 2016-04-11 |
| WO2012019427A8 (zh) | 2012-05-10 |
| CN102372716A (zh) | 2012-03-14 |
| AU2011288876A1 (en) | 2013-01-31 |
| PL2604610T3 (pl) | 2016-11-30 |
| CA2806324C (en) | 2019-02-19 |
| KR101829940B1 (ko) | 2018-02-19 |
| BR112013002220A2 (pt) | 2016-05-24 |
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