EA032697B1 - Амидогетероарилароилгидразидэтины - Google Patents
Амидогетероарилароилгидразидэтины Download PDFInfo
- Publication number
- EA032697B1 EA032697B1 EA201792445A EA201792445A EA032697B1 EA 032697 B1 EA032697 B1 EA 032697B1 EA 201792445 A EA201792445 A EA 201792445A EA 201792445 A EA201792445 A EA 201792445A EA 032697 B1 EA032697 B1 EA 032697B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- formula
- alkyl
- pyridin
- chloro
- hydrazinecarbonyl
- Prior art date
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- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 title abstract description 6
- 125000003435 aroyl group Chemical group 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- -1 2-chloro-6-methylbenzoyl Chemical group 0.000 claims description 61
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims description 14
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 230000008520 organization Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 16
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 11
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 abstract description 8
- 239000005483 tyrosine kinase inhibitor Substances 0.000 abstract description 8
- 238000002360 preparation method Methods 0.000 abstract description 7
- 208000035475 disorder Diseases 0.000 abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 2
- 239000002253 acid Substances 0.000 description 18
- 125000000623 heterocyclic group Chemical group 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 11
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- 125000003118 aryl group Chemical group 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 4
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 239000002585 base Substances 0.000 description 4
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- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
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- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 125000006574 non-aromatic ring group Chemical group 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- UKPHSBYFUYSAIM-UHFFFAOYSA-N 2-chloro-6-methylbenzohydrazide Chemical compound CC1=CC=CC(Cl)=C1C(=O)NN UKPHSBYFUYSAIM-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 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
- 125000004435 hydrogen atom Chemical class [H]* 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
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- 230000002401 inhibitory effect Effects 0.000 description 3
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- 230000003287 optical effect Effects 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 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
- 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
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
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- 101001004391 Drosophila melanogaster Protein jim lovell Proteins 0.000 description 2
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- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.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 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
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- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
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- XNQULTQRGBXLIA-UHFFFAOYSA-O phosphonic anhydride Chemical compound O[P+](O)=O XNQULTQRGBXLIA-UHFFFAOYSA-O 0.000 description 1
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- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
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- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
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- 108020003175 receptors Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
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- 239000011593 sulfur Substances 0.000 description 1
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- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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Classifications
-
- 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
Landscapes
- 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1953MU2015 | 2015-05-18 | ||
| PCT/IN2016/050142 WO2016185490A1 (en) | 2015-05-18 | 2016-05-18 | Novel amidoheteroaryl aroyl hydrazide ethynes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201792445A1 EA201792445A1 (ru) | 2018-04-30 |
| EA032697B1 true EA032697B1 (ru) | 2019-07-31 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201792445A EA032697B1 (ru) | 2015-05-18 | 2016-05-18 | Амидогетероарилароилгидразидэтины |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US10150733B2 (enExample) |
| EP (1) | EP3297991B1 (enExample) |
| JP (1) | JP6689887B2 (enExample) |
| KR (1) | KR20180011772A (enExample) |
| CN (1) | CN107709300A (enExample) |
| AU (1) | AU2016263311A1 (enExample) |
| BR (1) | BR112017024633A2 (enExample) |
| CA (1) | CA2985161A1 (enExample) |
| EA (1) | EA032697B1 (enExample) |
| ES (1) | ES2774501T3 (enExample) |
| MX (1) | MX2017014752A (enExample) |
| WO (1) | WO2016185490A1 (enExample) |
| ZA (1) | ZA201707664B (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS63243B1 (sr) | 2016-06-02 | 2022-06-30 | Sun Pharma Advanced Res Co Ltd | Lečenje parkinsonove bolesti |
| EA037697B1 (ru) * | 2016-06-02 | 2021-05-12 | Сан Фарма Адвансед Ресёрч Компани Лимитед | Лечение болезни паркинсона |
| WO2018167803A1 (en) * | 2017-03-15 | 2018-09-20 | Sun Pharma Advanced Research Company Limited | Novel amorphous dispersion of cyclopropanecarboxylic acid (5-{5-[ n'-(2-chloro-6-methylbenzoyl) hydrazinocarbonyl] -2-methyl-phenylethynyl}-pyridin-2-yl) amide |
| TWI831259B (zh) | 2018-06-15 | 2024-02-01 | 漢達生技醫藥股份有限公司 | 包含達沙替尼十二烷基硫酸鹽組合物的膠囊 |
Citations (2)
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|---|---|---|---|---|
| WO2007133560A2 (en) * | 2006-05-08 | 2007-11-22 | Ariad Pharmaceuticals, Inc. | Acetylenic heteroaryl compounds |
| WO2013127729A1 (en) * | 2012-02-27 | 2013-09-06 | Boehringer Ingelheim International Gmbh | 6 - alkynyl pyridines as smac mimetics |
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| WO2012089106A1 (zh) * | 2010-12-27 | 2012-07-05 | Sun Shuping | 作为蛋白激酶抑制剂的芳炔类衍生物及其医疗用途 |
| US9024021B2 (en) * | 2011-01-21 | 2015-05-05 | Sun Pharma Advanced Research Company Ltd. | Diarylacetylene hydrazide containing tyrosine kinase inhibitors |
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- 2016-05-18 CA CA2985161A patent/CA2985161A1/en not_active Abandoned
- 2016-05-18 KR KR1020177033739A patent/KR20180011772A/ko not_active Withdrawn
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- 2016-05-18 MX MX2017014752A patent/MX2017014752A/es unknown
- 2016-05-18 EA EA201792445A patent/EA032697B1/ru not_active IP Right Cessation
- 2016-05-18 US US15/574,967 patent/US10150733B2/en active Active
- 2016-05-18 JP JP2017560135A patent/JP6689887B2/ja not_active Expired - Fee Related
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2007133560A2 (en) * | 2006-05-08 | 2007-11-22 | Ariad Pharmaceuticals, Inc. | Acetylenic heteroaryl compounds |
| WO2013127729A1 (en) * | 2012-02-27 | 2013-09-06 | Boehringer Ingelheim International Gmbh | 6 - alkynyl pyridines as smac mimetics |
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| MX2017014752A (es) | 2018-03-23 |
| AU2016263311A1 (en) | 2017-11-30 |
| KR20180011772A (ko) | 2018-02-02 |
| JP6689887B2 (ja) | 2020-04-28 |
| EA201792445A1 (ru) | 2018-04-30 |
| EP3297991A1 (en) | 2018-03-28 |
| BR112017024633A2 (pt) | 2018-07-31 |
| EP3297991B1 (en) | 2020-01-29 |
| JP2018515550A (ja) | 2018-06-14 |
| ES2774501T3 (es) | 2020-07-21 |
| CN107709300A (zh) | 2018-02-16 |
| US10150733B2 (en) | 2018-12-11 |
| EP3297991A4 (en) | 2018-11-21 |
| WO2016185490A1 (en) | 2016-11-24 |
| US20180127372A1 (en) | 2018-05-10 |
| ZA201707664B (en) | 2019-08-28 |
| CA2985161A1 (en) | 2016-11-24 |
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