CA2904054A1 - Deuterated palbociclib - Google Patents
Deuterated palbociclib Download PDFInfo
- Publication number
- CA2904054A1 CA2904054A1 CA2904054A CA2904054A CA2904054A1 CA 2904054 A1 CA2904054 A1 CA 2904054A1 CA 2904054 A CA2904054 A CA 2904054A CA 2904054 A CA2904054 A CA 2904054A CA 2904054 A1 CA2904054 A1 CA 2904054A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- same
- disease
- hydrogen
- deuterium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- AHJRHEGDXFFMBM-UHFFFAOYSA-N palbociclib Chemical class N1=C2N(C3CCCC3)C(=O)C(C(=O)C)=C(C)C2=CN=C1NC(N=C1)=CC=C1N1CCNCC1 AHJRHEGDXFFMBM-UHFFFAOYSA-N 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 162
- 239000000203 mixture Substances 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 201000010099 disease Diseases 0.000 claims abstract description 25
- 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims description 80
- 229910052805 deuterium Inorganic materials 0.000 claims description 41
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 40
- 229940124597 therapeutic agent Drugs 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 12
- 230000000155 isotopic effect Effects 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
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- 208000034578 Multiple myelomas Diseases 0.000 claims description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 5
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 5
- 229960001467 bortezomib Drugs 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 102100031265 Chromodomain-helicase-DNA-binding protein 2 Human genes 0.000 claims description 4
- 101000777079 Homo sapiens Chromodomain-helicase-DNA-binding protein 2 Proteins 0.000 claims description 4
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- 201000011510 cancer Diseases 0.000 claims description 4
- 206010000830 Acute leukaemia Diseases 0.000 claims description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 3
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 3
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- 229960002932 anastrozole Drugs 0.000 claims description 3
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 claims description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 3
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- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 claims description 3
- 206010024627 liposarcoma Diseases 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 3
- 229960001756 oxaliplatin Drugs 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 3
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- 230000007815 allergy Effects 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 abstract description 8
- MHHOMHMNIRXARC-UHFFFAOYSA-N 1h-pyrido[2,3-d]pyrimidin-2-one Chemical class C1=CN=C2NC(=O)N=CC2=C1 MHHOMHMNIRXARC-UHFFFAOYSA-N 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 36
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229960004390 palbociclib Drugs 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
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- 239000007788 liquid Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
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- 239000002775 capsule Substances 0.000 description 5
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- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 5
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- 230000002588 toxic effect Effects 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
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- 125000004432 carbon atom Chemical group C* 0.000 description 4
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 4
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
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Classifications
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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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/062—Organo-phosphoranes without P-C bonds
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361787540P | 2013-03-15 | 2013-03-15 | |
| US61/787,540 | 2013-03-15 | ||
| PCT/US2014/024564 WO2014150925A2 (en) | 2013-03-15 | 2014-03-12 | Deuterated palbociclib |
Publications (1)
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|---|---|
| CA2904054A1 true CA2904054A1 (en) | 2014-09-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2904054A Abandoned CA2904054A1 (en) | 2013-03-15 | 2014-03-12 | Deuterated palbociclib |
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| Country | Link |
|---|---|
| US (3) | US20160024084A1 (OSRAM) |
| EP (2) | EP2970209B1 (OSRAM) |
| JP (1) | JP2016512831A (OSRAM) |
| AU (1) | AU2014235462C1 (OSRAM) |
| CA (1) | CA2904054A1 (OSRAM) |
| EA (2) | EA032094B1 (OSRAM) |
| MX (1) | MX2015012741A (OSRAM) |
| WO (1) | WO2014150925A2 (OSRAM) |
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| CN105111201B (zh) * | 2014-10-16 | 2017-01-11 | 上海页岩科技有限公司 | 5-甲基-2-(吡啶-2-基氨基)-8H-吡啶并[2,3-d]嘧啶-7-酮化合物 |
| WO2016092442A1 (en) * | 2014-12-08 | 2016-06-16 | Sun Pharmaceutical Industries Limited | Processes for the preparation of crystalline forms of palbociclib acetate |
| CN104892604B (zh) * | 2015-06-19 | 2016-08-24 | 北京康立生医药技术开发有限公司 | 一种cdk4抑制剂的合成方法 |
| CN105153149B (zh) * | 2015-07-29 | 2017-09-19 | 江苏中邦制药有限公司 | 一种选择性激酶抑制剂Palbociclib的制备方法 |
| EP3386981B1 (en) * | 2015-12-13 | 2021-10-13 | Hangzhou Innogate Pharma Co., Ltd. | Heterocycles useful as anti-cancer agents |
| CN106986871B (zh) * | 2017-03-29 | 2019-02-26 | 浙江同源康医药股份有限公司 | 一种氘代Palbociclib的晶型及其制备方法和应用 |
| CN106967064B (zh) * | 2017-03-29 | 2018-03-23 | 郑州泰基鸿诺医药股份有限公司 | 氘代Palbociclib的衍生物、制备方法及其应用 |
| SG11202100429TA (en) | 2018-07-27 | 2021-02-25 | California Inst Of Techn | Cdk inhibitors and uses thereof |
| WO2020114519A1 (zh) * | 2018-12-07 | 2020-06-11 | 杭州英创医药科技有限公司 | 作为cdk-hdac双通路抑制剂的杂环化合物 |
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| LV15575A (lv) | 2019-12-20 | 2021-06-20 | Latvijas Organiskās Sintēzes Institūts | Selenofēnhromēnu deiterēti analogi, to iegūšana un izmantošana |
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| US20090030005A1 (en) | 2007-07-19 | 2009-01-29 | Amgen Inc. | Combinations for the treatment of cancer |
| US9259399B2 (en) | 2007-11-07 | 2016-02-16 | Cornell University | Targeting CDK4 and CDK6 in cancer therapy |
| EP2242493B1 (en) * | 2008-01-22 | 2013-06-05 | Concert Pharmaceuticals Inc. | Derivatives of gefitinib |
| CA2738925A1 (en) | 2008-10-01 | 2010-04-08 | The University Of North Carolina At Chapel Hill | Hematopoietic protection against chemotherapeutic compounds using selective cyclin-dependent kinase 4/6 inhibitors |
| JP2012504645A (ja) | 2008-10-01 | 2012-02-23 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | 健康な細胞に対する電離放射線の影響を低下させる又は防止するための医薬組成物 |
| EP3718560A3 (en) | 2009-05-13 | 2020-12-09 | The University of North Carolina at Chapel Hill | Cyclin dependent kinase inhibitors and methods of use |
| UY33226A (es) * | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina deuterada como inhibidores de la cdk4/6 |
| US20130035336A1 (en) | 2010-04-13 | 2013-02-07 | Novartis Ag | Combination comprising a cyclin dependent kinase 4 or cyclin dependent kinase (cdk4/6) inhibitor for treating cancer |
| CN101967142B (zh) * | 2010-05-17 | 2012-05-30 | 苏州波锐生物医药科技有限公司 | 噻唑酰胺类化合物及其在治疗恶性肿瘤中的药物用途 |
| US9808461B2 (en) | 2010-11-17 | 2017-11-07 | The University Of North Carolina At Chapel Hill | Protection of renal tissues from ischemia through inhibition of the proliferative kinases CDK4 and CDK6 |
-
2014
- 2014-03-12 JP JP2016501574A patent/JP2016512831A/ja active Pending
- 2014-03-12 WO PCT/US2014/024564 patent/WO2014150925A2/en not_active Ceased
- 2014-03-12 EP EP14769343.6A patent/EP2970209B1/en active Active
- 2014-03-12 MX MX2015012741A patent/MX2015012741A/es unknown
- 2014-03-12 EA EA201591628A patent/EA032094B1/ru not_active IP Right Cessation
- 2014-03-12 EA EA201892726A patent/EA201892726A1/ru unknown
- 2014-03-12 AU AU2014235462A patent/AU2014235462C1/en not_active Ceased
- 2014-03-12 CA CA2904054A patent/CA2904054A1/en not_active Abandoned
- 2014-03-12 US US14/775,854 patent/US20160024084A1/en not_active Abandoned
- 2014-03-12 EP EP18205631.7A patent/EP3492470A1/en not_active Withdrawn
-
2017
- 2017-06-29 US US15/636,976 patent/US20180051022A1/en not_active Abandoned
-
2018
- 2018-11-13 US US16/189,304 patent/US20190225605A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP2970209A2 (en) | 2016-01-20 |
| AU2014235462C1 (en) | 2018-11-01 |
| US20190225605A1 (en) | 2019-07-25 |
| WO2014150925A2 (en) | 2014-09-25 |
| EA201892726A1 (ru) | 2019-04-30 |
| EP2970209A4 (en) | 2016-08-31 |
| MX2015012741A (es) | 2016-02-19 |
| EP3492470A1 (en) | 2019-06-05 |
| US20180051022A1 (en) | 2018-02-22 |
| EP2970209B1 (en) | 2018-12-26 |
| EA201591628A1 (ru) | 2016-03-31 |
| WO2014150925A3 (en) | 2014-12-04 |
| AU2014235462B2 (en) | 2018-05-17 |
| AU2014235462A1 (en) | 2015-09-17 |
| US20160024084A1 (en) | 2016-01-28 |
| EA032094B1 (ru) | 2019-04-30 |
| JP2016512831A (ja) | 2016-05-09 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request |
Effective date: 20190121 |
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| FZDE | Discontinued |
Effective date: 20210831 |