JP6689887B2 - 新規アミドヘテロアリールアロイルヒドラジドエチン - Google Patents
新規アミドヘテロアリールアロイルヒドラジドエチン Download PDFInfo
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- JP6689887B2 JP6689887B2 JP2017560135A JP2017560135A JP6689887B2 JP 6689887 B2 JP6689887 B2 JP 6689887B2 JP 2017560135 A JP2017560135 A JP 2017560135A JP 2017560135 A JP2017560135 A JP 2017560135A JP 6689887 B2 JP6689887 B2 JP 6689887B2
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- formula
- methyl
- alkyl
- acid
- hydrazinocarbonyl
- Prior art date
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- HSFWRNGVRCDJHI-UHFFFAOYSA-N Acetylene Chemical compound C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 title 2
- 150000001875 compounds Chemical class 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- ZLDCIFNKBZSDPZ-UHFFFAOYSA-N N'-[3-[2-(6-aminopyridin-3-yl)ethynyl]-4-methylbenzoyl]-2-chloro-6-methylbenzohydrazide Chemical compound CC1=C(C(=CC=C1)Cl)C(=O)NNC(=O)C2=CC(=C(C=C2)C)C#CC3=CN=C(C=C3)N ZLDCIFNKBZSDPZ-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- -1 4-[(methyl-1-piperazinyl) methyl] -N- [4-methyl-3-[[4- (3-pyridinyl) -2-pyrimidinyl] amino ] -Phenyl] benzamido Chemical group 0.000 description 48
- 238000011282 treatment Methods 0.000 description 21
- 239000002253 acid Substances 0.000 description 18
- 125000000623 heterocyclic group Chemical group 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
- 238000000034 method Methods 0.000 description 14
- 125000005842 heteroatom Chemical group 0.000 description 13
- 125000001072 heteroaryl group Chemical group 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 7
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- 150000001408 amides Chemical class 0.000 description 7
- 150000008064 anhydrides Chemical class 0.000 description 7
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
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- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
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- 125000006574 non-aromatic ring group Chemical group 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 5
- NZXDVMRNUSTTGO-UHFFFAOYSA-N N-[5-[2-[5-[[(2-chloro-6-methylbenzoyl)amino]carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound ClC1=C(C(=O)NNC(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(=O)C2CC2)C)C(=CC=C1)C NZXDVMRNUSTTGO-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
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- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 5
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 4
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 4
- YDNKKVBURJSGKM-UHFFFAOYSA-N N-[5-[2-[2-methyl-5-[[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]carbamoyl]phenyl]ethynyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound CC1=C(C=C(C=C1)C(=O)NNC(C1=CC(=CC(=C1)C(F)(F)F)N1C=NC(=C1)C)=O)C#CC=1C=CC(=NC=1)NC(=O)C1CC1 YDNKKVBURJSGKM-UHFFFAOYSA-N 0.000 description 4
- PSWVXKCLQUYTCY-UHFFFAOYSA-N N-[5-[2-[2-methyl-5-[[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]carbamoyl]phenyl]ethynyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound CC1=C(C=C(C=C1)C(=O)NNC(C1=CC=C(C=C1)CN1CCN(CC1)C)=O)C#CC=1C=CC(=NC=1)NC(=O)C1CC1 PSWVXKCLQUYTCY-UHFFFAOYSA-N 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
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- 230000003389 potentiating effect Effects 0.000 description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
- AUIIWQULVSVOFU-UHFFFAOYSA-N 1-[5-[2-[5-[[(2-chloro-6-methylbenzoyl)amino]carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]-3-cyclopropylurea Chemical compound ClC1=C(C(=O)NNC(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(=O)NC2CC2)C)C(=CC=C1)C AUIIWQULVSVOFU-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 3
- IFLOEAVTCNHYAU-UHFFFAOYSA-N N-[5-[2-[5-[[(2-chloro-6-methylbenzoyl)amino]carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]acetamide Chemical compound ClC1=C(C(=O)NNC(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(C)=O)C)C(=CC=C1)C IFLOEAVTCNHYAU-UHFFFAOYSA-N 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 3
- 229960002411 imatinib Drugs 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
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- 238000002360 preparation method Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000003107 substituted aryl group Chemical group 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
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- IPKJEEQHPASXLO-UHFFFAOYSA-N N-[5-[2-[5-[[(2-chloro-6-methylbenzoyl)amino]carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]-2-(dimethylamino)acetamide Chemical compound ClC1=C(C(=O)NNC(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(CN(C)C)=O)C)C(=CC=C1)C IPKJEEQHPASXLO-UHFFFAOYSA-N 0.000 description 2
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- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
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- GDJTZJNZNNFYHX-UHFFFAOYSA-N 3-[2-[6-(cyclopropanecarbonylamino)pyridin-3-yl]ethynyl]-4-methylbenzoic acid Chemical compound C1(CC1)C(=O)NC1=CC=C(C=N1)C#CC=1C=C(C(=O)O)C=CC=1C GDJTZJNZNNFYHX-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- 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
- C07B43/00—Formation or introduction of functional groups containing nitrogen
- C07B43/06—Formation or introduction of functional groups containing nitrogen of amide groups
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1953MU2015 | 2015-05-18 | ||
| IN1953/MUM/2015 | 2015-05-18 | ||
| PCT/IN2016/050142 WO2016185490A1 (en) | 2015-05-18 | 2016-05-18 | Novel amidoheteroaryl aroyl hydrazide ethynes |
Publications (3)
| Publication Number | Publication Date |
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| JP2018515550A JP2018515550A (ja) | 2018-06-14 |
| JP2018515550A5 JP2018515550A5 (enExample) | 2019-05-09 |
| JP6689887B2 true JP6689887B2 (ja) | 2020-04-28 |
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| JP (1) | JP6689887B2 (enExample) |
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| WO (1) | WO2016185490A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA037697B1 (ru) * | 2016-06-02 | 2021-05-12 | Сан Фарма Адвансед Ресёрч Компани Лимитед | Лечение болезни паркинсона |
| LT3463351T (lt) | 2016-06-02 | 2022-06-10 | Sun Pharma Advanced Research Company Limited | Parkinsono ligos gydymas |
| EP3596049A4 (en) * | 2017-03-15 | 2021-01-13 | Sun Pharma Advanced Research Company Limited | NEW AMORPHIC DISPERSION OF CYCLOPROPANECARBOXYLIC ACID (5- {5- [N '- (2-CHLORO-6-METHYLBENZOYL) HYDRAZINOCARBONYL] -2-METHYL-PHENYLETHYNYL} -PYRIDIN-2-AMIDE |
| TWI787523B (zh) | 2018-06-15 | 2022-12-21 | 漢達生技醫藥股份有限公司 | 達沙替尼十二烷基硫酸鹽之結晶 |
| JP2024063350A (ja) * | 2022-10-26 | 2024-05-13 | Ｔｏｐｐａｎホールディングス株式会社 | 電極触媒層及び膜電極接合体 |
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| BRPI0710328A2 (pt) | 2006-05-08 | 2011-08-09 | Ariad Pharma Inc | composto da fórmula i, um tautomer da mesma, ou um sal farmaceuticamente aceitável, hidrato ou outro solvato do mesmo e método para o tratamento de cáncer em um mamìfero necessitado do mesmo e composição |
| CN103370324B (zh) * | 2010-12-27 | 2016-05-18 | 孙树萍 | 作为蛋白激酶抑制剂的芳炔类衍生物及其医疗用途 |
| EP2665709B1 (en) * | 2011-01-21 | 2016-12-07 | Sun Pharma Advanced Research Company Limited | Diarylacetylene hydrazide containing tyrosine kinase inhibitors |
| US8859541B2 (en) | 2012-02-27 | 2014-10-14 | Boehringer Ingelheim International Gmbh | 6-alkynylpyridines |
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2016
- 2016-05-18 CA CA2985161A patent/CA2985161A1/en not_active Abandoned
- 2016-05-18 EA EA201792445A patent/EA032697B1/ru not_active IP Right Cessation
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- 2016-05-18 MX MX2017014752A patent/MX2017014752A/es unknown
- 2016-05-18 AU AU2016263311A patent/AU2016263311A1/en not_active Abandoned
- 2016-05-18 WO PCT/IN2016/050142 patent/WO2016185490A1/en not_active Ceased
- 2016-05-18 KR KR1020177033739A patent/KR20180011772A/ko not_active Withdrawn
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- 2016-05-18 BR BR112017024633A patent/BR112017024633A2/pt not_active Application Discontinuation
- 2016-05-18 CN CN201680028615.2A patent/CN107709300A/zh not_active Withdrawn
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| EP3297991A4 (en) | 2018-11-21 |
| EP3297991B1 (en) | 2020-01-29 |
| US20180127372A1 (en) | 2018-05-10 |
| BR112017024633A2 (pt) | 2018-07-31 |
| EA032697B1 (ru) | 2019-07-31 |
| JP2018515550A (ja) | 2018-06-14 |
| KR20180011772A (ko) | 2018-02-02 |
| CA2985161A1 (en) | 2016-11-24 |
| CN107709300A (zh) | 2018-02-16 |
| EA201792445A1 (ru) | 2018-04-30 |
| US10150733B2 (en) | 2018-12-11 |
| MX2017014752A (es) | 2018-03-23 |
| ZA201707664B (en) | 2019-08-28 |
| ES2774501T3 (es) | 2020-07-21 |
| EP3297991A1 (en) | 2018-03-28 |
| WO2016185490A1 (en) | 2016-11-24 |
| AU2016263311A1 (en) | 2017-11-30 |
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