ES2644758T3 - Moduladores de PKM2 y métodos para su uso - Google Patents
Moduladores de PKM2 y métodos para su uso Download PDFInfo
- Publication number
- ES2644758T3 ES2644758T3 ES13847643.7T ES13847643T ES2644758T3 ES 2644758 T3 ES2644758 T3 ES 2644758T3 ES 13847643 T ES13847643 T ES 13847643T ES 2644758 T3 ES2644758 T3 ES 2644758T3
- Authority
- ES
- Spain
- Prior art keywords
- nmr
- mhz
- cd3od
- tfa
- pkm2
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims description 3
- 101001091538 Homo sapiens Pyruvate kinase PKM Proteins 0.000 title description 54
- 102100034911 Pyruvate kinase PKM Human genes 0.000 title description 54
- 150000001875 compounds Chemical class 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 382
- 238000005160 1H NMR spectroscopy Methods 0.000 description 246
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 124
- 238000005481 NMR spectroscopy Methods 0.000 description 54
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 53
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 22
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 12
- 125000005843 halogen group Chemical group 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- -1 amino acid ester Chemical class 0.000 description 2
- 125000004103 aminoalkyl group Chemical group 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 101100495917 Arabidopsis thaliana ATRX gene Proteins 0.000 description 1
- XPYBSIWDXQFNMH-UHFFFAOYSA-N D-fructose 1,6-bisphosphate Natural products OP(=O)(O)OCC(O)C(O)C(O)C(=O)COP(O)(O)=O XPYBSIWDXQFNMH-UHFFFAOYSA-N 0.000 description 1
- 102100020870 La-related protein 6 Human genes 0.000 description 1
- 108050008265 La-related protein 6 Proteins 0.000 description 1
- 101150020251 NR13 gene Proteins 0.000 description 1
- 101000595993 Phyllomedusa sauvagei Phylloseptin-S1 Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- KYIKRXIYLAGAKQ-UHFFFAOYSA-N abcn Chemical compound C1CCCCC1(C#N)N=NC1(C#N)CCCCC1 KYIKRXIYLAGAKQ-UHFFFAOYSA-N 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- RNBGYGVWRKECFJ-ZXXMMSQZSA-N alpha-D-fructofuranose 1,6-bisphosphate Chemical compound O[C@H]1[C@H](O)[C@](O)(COP(O)(O)=O)O[C@@H]1COP(O)(O)=O RNBGYGVWRKECFJ-ZXXMMSQZSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- RNBGYGVWRKECFJ-UHFFFAOYSA-N fructose-1,6-phosphate Natural products OC1C(O)C(O)(COP(O)(O)=O)OC1COP(O)(O)=O RNBGYGVWRKECFJ-UHFFFAOYSA-N 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
-
- 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
- A61K31/41—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
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/16—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/38—Nitrogen atoms
-
- 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
-
- 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
- C07D403/02—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
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2
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)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261714659P | 2012-10-16 | 2012-10-16 | |
| US201261714659P | 2012-10-16 | ||
| US201361875855P | 2013-09-10 | 2013-09-10 | |
| US201361875855P | 2013-09-10 | ||
| PCT/US2013/065296 WO2014062838A2 (en) | 2012-10-16 | 2013-10-16 | Pkm2 modulators and methods for their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2644758T3 true ES2644758T3 (es) | 2017-11-30 |
Family
ID=50488890
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13847643.7T Active ES2644758T3 (es) | 2012-10-16 | 2013-10-16 | Moduladores de PKM2 y métodos para su uso |
Country Status (6)
| Country | Link |
|---|---|
| US (5) | US9394257B2 (enExample) |
| EP (1) | EP2909181B1 (enExample) |
| JP (7) | JP6243918B2 (enExample) |
| DK (1) | DK2909181T3 (enExample) |
| ES (1) | ES2644758T3 (enExample) |
| WO (1) | WO2014062838A2 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2909181B1 (en) * | 2012-10-16 | 2017-08-09 | Tolero Pharmaceuticals, Inc. | Pkm2 modulators and methods for their use |
| AR111295A1 (es) | 2017-03-20 | 2019-06-26 | Forma Therapeutics Inc | Composiciones de pirrolopirrol como activadores de piruvato quinasa (pkr) |
| US20200237766A1 (en) * | 2017-10-13 | 2020-07-30 | Tolero Pharmaceuticals, Inc. | Pkm2 activators in combination with reactive oxygen species for treatment of cancer |
| WO2020061255A1 (en) | 2018-09-19 | 2020-03-26 | Forma Therapeutics, Inc. | Activating pyruvate kinase r |
| US20200129485A1 (en) | 2018-09-19 | 2020-04-30 | Forma Therapeutics, Inc. | Treating sickle cell disease with a pyruvate kinase r activating compound |
| JP2022527451A (ja) * | 2019-03-22 | 2022-06-02 | スミトモ ダイニッポン ファーマ オンコロジー， インコーポレイテッド | Ｐｋｍ２モジュレーターおよびその使用方法 |
| AU2020245437A1 (en) * | 2019-03-22 | 2021-09-30 | Sumitomo Pharma Oncology, Inc. | Compositions comprising PKM2 modulators and methods of treatment using the same |
| EP4010320A4 (en) | 2019-08-06 | 2023-08-16 | Biocryst Pharmaceuticals, Inc. | Process-scale synthesis of a plasma kallikrein inhibitor |
| MX2022003025A (es) | 2019-09-19 | 2022-04-07 | Forma Therapeutics Inc | Activacion de la piruvato cinasa r. |
| US12128035B2 (en) | 2021-03-19 | 2024-10-29 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
Family Cites Families (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2779780A (en) | 1955-03-01 | 1957-01-29 | Du Pont | 1, 4-diamino-2, 3-dicyano-1, 4-bis (substituted mercapto) butadienes and their preparation |
| GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| JP2861087B2 (ja) * | 1989-08-08 | 1999-02-24 | 三菱化学株式会社 | Ｎ―アシル‐５‐ピラゾールカルボキサミド類およびこれを有効成分とする殺虫、殺ダニ剤 |
| FI941572L (fi) | 1991-10-07 | 1994-05-27 | Oncologix Inc | Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenetelmä |
| CA2372813A1 (en) | 1992-02-06 | 1993-08-19 | L.L. Houston | Biosynthetic binding protein for cancer marker |
| IT1255527B (it) * | 1992-09-29 | 1995-11-09 | Mini Ricerca Scient Tecnolog | Pirazolcarbossammidi ad attivita' insetticida ed acaricida |
| US6177401B1 (en) | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
| US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| EP0647450A1 (en) | 1993-09-09 | 1995-04-12 | BEHRINGWERKE Aktiengesellschaft | Improved prodrugs for enzyme mediated activation |
| IL112248A0 (en) | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
| US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| CA2218503C (en) | 1995-04-20 | 2001-07-24 | Pfizer Inc. | Arylsulfonyl hydroxamic acid derivatives |
| US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| GB9520822D0 (en) | 1995-10-11 | 1995-12-13 | Wellcome Found | Therapeutically active compounds |
| DK0780386T3 (da) | 1995-12-20 | 2003-02-03 | Hoffmann La Roche | Matrixmetalloproteaseinhibitorer |
| DE19600097C1 (de) | 1996-01-03 | 1997-07-31 | Siemens Ag | Verfahren und Vorrichtung zur Bestimmung einer Flüssigkeitshöhe mit Hilfe von Ultraschallimpulsen |
| NZ331191A (en) | 1996-03-05 | 2000-03-27 | Zeneca Ltd | 4-anilinoquinazoline derivatives and pharmaceutical compositions thereof |
| EP0818442A3 (en) | 1996-07-12 | 1998-12-30 | Pfizer Inc. | Cyclic sulphone derivatives as inhibitors of metalloproteinases and of the production of tumour necrosis factor |
| AR007855A1 (es) | 1996-07-13 | 1999-11-24 | Glaxo Group Ltd | Compuestos heterociclicos fusionados como inhibidores de proteina tirosina quinasa, sus metodos de preparacion, intermediarios, uso en medicinay composiciones farmaceuticas que los contienen |
| US6391874B1 (en) | 1996-07-13 | 2002-05-21 | Smithkline Beecham Corporation | Fused heterocyclic compounds as protein tyrosine kinase inhibitors |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| EP0923585B1 (en) | 1996-07-18 | 2002-05-08 | Pfizer Inc. | Phosphinate based inhibitors of matrix metalloproteases |
| EP0922030A1 (en) | 1996-08-23 | 1999-06-16 | Pfizer Inc. | Arylsulfonylamino hydroxamic acid derivatives |
| ID18494A (id) | 1996-10-02 | 1998-04-16 | Novartis Ag | Turunan pirazola leburan dan proses pembuatannya |
| US6077864A (en) | 1997-01-06 | 2000-06-20 | Pfizer Inc. | Cyclic sulfone derivatives |
| HUP0000852A2 (hu) | 1997-02-03 | 2001-05-28 | Pfizer Products Inc. | Aril-szulfonil-amino-hidroxámsav-származékok, valamint e vegyületeket tartalmazó gyógyászati készítmények |
| JP2000507975A (ja) | 1997-02-07 | 2000-06-27 | ファイザー・インク | Ｎ−ヒドロキシ−β−スルホニルプロピオンアミド誘導体類及びそれらのマトリックスメタロプロテイナーゼ阻害薬としての使用 |
| NZ336836A (en) | 1997-02-11 | 2001-02-23 | Pfizer | Arylsulfonyl hydroxamic acid derivatives suitable for a broad range of medicinal treatments |
| CA2289102A1 (en) | 1997-05-07 | 1998-11-12 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| CA2291709A1 (en) | 1997-05-30 | 1998-12-03 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| TR200000368T2 (tr) | 1997-08-08 | 2000-07-21 | Pfizer Products Inc. | Ariloksiariarilsülfonilamino hidroksamik asit türevleri. |
| DE69838172T2 (de) | 1997-08-22 | 2008-04-10 | Astrazeneca Ab | Oxindolylchinazolinderivate als angiogenesehemmer |
| AU744939B2 (en) | 1997-09-26 | 2002-03-07 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| SK6652000A3 (en) | 1997-11-11 | 2002-05-09 | Pfizer Prod Inc | Thienopyrimidine and thienopyridine derivatives useful as anticancer agents |
| GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| GB9800575D0 (en) | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| GB9801690D0 (en) | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
| PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
| PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
| KR100743287B1 (ko) | 1998-05-29 | 2007-07-26 | 수젠, 인크. | 피롤기로 치환된 2-인돌리논 단백질 인산화 효소 억제제 |
| UA60365C2 (uk) | 1998-06-04 | 2003-10-15 | Пфайзер Продактс Інк. | Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця |
| EP1004578B1 (en) | 1998-11-05 | 2004-02-25 | Pfizer Products Inc. | 5-oxo-pyrrolidine-2-carboxylic acid hydroxamide derivatives |
| JP2002532415A (ja) | 1998-12-16 | 2002-10-02 | ワーナー−ランバート・カンパニー | Ｍｅｋ阻害剤による関節炎の治療 |
| UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| GB9912961D0 (en) | 1999-06-03 | 1999-08-04 | Pfizer Ltd | Metalloprotease inhibitors |
| JP2001172261A (ja) * | 1999-12-20 | 2001-06-26 | Mitsubishi Chemicals Corp | ピラゾールカルボン酸アミド類、およびこれを有効成分とする殺虫、殺ダニ剤 |
| HRP20020751B1 (hr) | 2000-02-15 | 2011-01-31 | Sugen | Pirolom supstituirani 2-indolinoni kao inhibitori protein kinaze |
| AU7349801A (en) | 2000-07-19 | 2002-01-30 | Warner Lambert Co | Oxygenated esters of 4-iodo phenylamino benzhydroxamic acids |
| US6660731B2 (en) * | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| AU2001290912A1 (en) * | 2000-09-15 | 2002-03-26 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US6995162B2 (en) | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| JP2002363164A (ja) * | 2001-04-06 | 2002-12-18 | Mitsubishi Chemicals Corp | ピラゾールカルボキサミド類、その中間体およびこれを有効成分とする有害生物防除剤 |
| CN1511142A (zh) * | 2001-04-06 | 2004-07-07 | 日本农药株式会社 | 吡唑酰胺衍生物及用于制备该衍生物的中间体、以该衍生物为活性成分的有害生物防治剂 |
| WO2004078163A2 (en) | 2003-02-28 | 2004-09-16 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| CA2478065C (en) | 2002-03-08 | 2013-01-08 | Eisai Co. Ltd. | Macrocyclic compounds useful as pharmaceuticals |
| SG2013013339A (en) | 2002-03-13 | 2014-12-30 | Array Biopharma Inc | N3 alkylated benzimidazole derivatives as mek inhibitors |
| US20070060589A1 (en) * | 2004-12-21 | 2007-03-15 | Purandare Ashok V | Inhibitors of protein arginine methyl transferases |
| MX2007012463A (es) * | 2005-04-08 | 2007-11-07 | Pfizer Prod Inc | Heteroarilamidas[3.1.0]biciclicas como inhibidores del transporte de glicina de tipo i. |
| BRPI0609464A2 (pt) * | 2005-05-23 | 2010-04-13 | Japan Tobacco Inc | composto de pirazol e agente terapêutico para diabetes compreendendo o mesmo |
| MX2008002114A (es) | 2005-07-21 | 2008-04-17 | Ardea Biosciences Inc | Inhibidores de n-(arilamino)-sulfonamida de mek. |
| JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| WO2009025781A1 (en) | 2007-08-16 | 2009-02-26 | Beth Israel Deaconess Medical Center | Activators of pyruvate kinase m2 and methods of treating disease |
| JPWO2009028280A1 (ja) * | 2007-08-29 | 2010-11-25 | 三井化学アグロ株式会社 | ピラゾールカルボン酸誘導体及びその製造方法、並びに殺菌剤 |
| BRPI0816769A2 (pt) | 2007-09-12 | 2016-11-29 | Hoffmann La Roche | combinações de compostos inibidores de fosfoinositida 3-cinase e agentes quimioterapêuticos, e métodos de uso |
| WO2009055730A1 (en) | 2007-10-25 | 2009-04-30 | Genentech, Inc. | Process for making thienopyrimidine compounds |
| ES2620634T3 (es) | 2008-10-09 | 2017-06-29 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Activadores de piruvato quinasa humana |
| US8637550B2 (en) | 2008-11-17 | 2014-01-28 | Boehringer Ingelheim International Gmbh | Heteroaryl diamide compounds useful as MMP-13 inhibitors |
| WO2010083246A1 (en) | 2009-01-15 | 2010-07-22 | Amgen Inc. | Fluoroisoquinoline substituted thiazole compounds and methods of use |
| JP5756457B2 (ja) * | 2009-04-06 | 2015-07-29 | アジオス ファーマシューティカルズ， インコーポレイテッド | ピルビン酸キナーゼｍ２調節剤、治療組成物および関連する使用方法 |
| PL2427441T3 (pl) | 2009-05-04 | 2017-06-30 | Agios Pharmaceuticals, Inc. | Aktywatory PKM2 do stosowania w leczeniu raka |
| US8349832B2 (en) | 2009-09-02 | 2013-01-08 | Canthera Therapeutics | Compounds and compositions for treating cancer |
| WO2011069298A1 (en) | 2009-12-11 | 2011-06-16 | F. Hoffmann-La Roche Ag | Novel cyclopropane indolinone derivatives |
| CN103269706B (zh) | 2010-09-30 | 2015-06-24 | 黄奇英 | 抗癌萃取物及化合物 |
| WO2012056319A1 (en) | 2010-10-27 | 2012-05-03 | Dynamix Pharmaceuticals Ltd. | Sulfonamides for the modulation of pkm2 |
| US9221792B2 (en) * | 2010-12-17 | 2015-12-29 | Agios Pharmaceuticals, Inc | N-(4-(azetidine-1-carbonyl) phenyl)-(hetero-) arylsulfonamide derivatives as pyruvate kinase M2 (PMK2) modulators |
| WO2012088314A1 (en) | 2010-12-21 | 2012-06-28 | Agios Pharmaceuticals, Inc. | Bicyclic pkm2 activators |
| TWI549947B (zh) | 2010-12-29 | 2016-09-21 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
| EP2497775A1 (en) | 2011-03-11 | 2012-09-12 | Ruprecht-Karls-Universität Heidelberg | Ferrocene-based compounds and their use as ROS regulating prodrugs |
| WO2012160447A1 (en) * | 2011-05-25 | 2012-11-29 | Dynamix Pharmaceuticals Ltd. | 3, 5 -diphenyl- substituted pyrazolines for the treatment of cancer, proliferative, inflammatory or autoimmune diseases |
| WO2013005157A1 (en) | 2011-07-05 | 2013-01-10 | Lupin Limited | Sulfone derivatives and their use as pkm2 modulators for the treatment of cancer |
| EP2909181B1 (en) * | 2012-10-16 | 2017-08-09 | Tolero Pharmaceuticals, Inc. | Pkm2 modulators and methods for their use |
| NZ707778A (en) | 2012-11-08 | 2019-03-29 | Agios Pharmaceuticals Inc | Therapeutic compounds and compositions and their use as pkm2 modulators |
| US9447054B2 (en) | 2014-01-15 | 2016-09-20 | Korea Institute Of Radiological & Medical Sciences | Anticancer supplement agent including benzo[D]oxazol derivative as effective ingredient |
-
2013
- 2013-10-16 EP EP13847643.7A patent/EP2909181B1/en active Active
- 2013-10-16 ES ES13847643.7T patent/ES2644758T3/es active Active
- 2013-10-16 US US14/435,976 patent/US9394257B2/en active Active
- 2013-10-16 DK DK13847643.7T patent/DK2909181T3/da active
- 2013-10-16 JP JP2015537799A patent/JP6243918B2/ja not_active Expired - Fee Related
- 2013-10-16 WO PCT/US2013/065296 patent/WO2014062838A2/en not_active Ceased
-
2016
- 2016-06-15 US US15/183,581 patent/US10207996B2/en active Active
-
2017
- 2017-10-20 JP JP2017203963A patent/JP6526767B2/ja not_active Expired - Fee Related
-
2018
- 2018-10-01 JP JP2018186629A patent/JP2019023209A/ja not_active Withdrawn
- 2018-12-19 US US16/226,599 patent/US10472328B2/en active Active
-
2019
- 2019-09-26 US US16/584,912 patent/US10766865B2/en active Active
-
2020
- 2020-03-03 JP JP2020035656A patent/JP2020105190A/ja not_active Withdrawn
- 2020-03-03 JP JP2020035657A patent/JP2020097631A/ja not_active Withdrawn
- 2020-07-15 US US16/930,254 patent/US20210002233A1/en not_active Abandoned
-
2021
- 2021-07-21 JP JP2021120679A patent/JP7128331B2/ja not_active Expired - Fee Related
- 2021-08-06 JP JP2021129580A patent/JP2021181467A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20200109120A1 (en) | 2020-04-09 |
| US10207996B2 (en) | 2019-02-19 |
| WO2014062838A2 (en) | 2014-04-24 |
| JP2021176878A (ja) | 2021-11-11 |
| JP2020105190A (ja) | 2020-07-09 |
| US20170015631A1 (en) | 2017-01-19 |
| US10472328B2 (en) | 2019-11-12 |
| JP7128331B2 (ja) | 2022-08-30 |
| US20190119219A1 (en) | 2019-04-25 |
| JP2021181467A (ja) | 2021-11-25 |
| EP2909181B1 (en) | 2017-08-09 |
| JP6243918B2 (ja) | 2017-12-06 |
| JP2015536325A (ja) | 2015-12-21 |
| EP2909181A2 (en) | 2015-08-26 |
| EP2909181A4 (en) | 2016-03-23 |
| JP2018009036A (ja) | 2018-01-18 |
| US20150344436A1 (en) | 2015-12-03 |
| US9394257B2 (en) | 2016-07-19 |
| WO2014062838A3 (en) | 2014-10-16 |
| JP6526767B2 (ja) | 2019-06-05 |
| US20210002233A1 (en) | 2021-01-07 |
| JP2020097631A (ja) | 2020-06-25 |
| JP2019023209A (ja) | 2019-02-14 |
| DK2909181T3 (da) | 2017-11-20 |
| US10766865B2 (en) | 2020-09-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2018287777B2 (en) | SSAO inhibitor | |
| AU2021277619B2 (en) | Substituted fused bi- or tri- heterocyclic compounds as ehmt2 inhibitors | |
| JP2022110080A (ja) | Ｅｈｍｔ２阻害剤としてのアミン置換複素環化合物およびその使用方法 | |
| ES2691068T3 (es) | Compuestos de indol e indazol como inhibidores de la necrosis celular | |
| AR091176A1 (es) | Pirrodilina-2-carboxamidas sustituidas | |
| CN119490431A (zh) | Tead转录因子的新型小分子抑制剂 | |
| AR067346A1 (es) | Derivados de bencimidazol | |
| AR089134A1 (es) | Arilos y heteroarilos biciclicos inhibidores de los canales de sodio | |
| ES2532853T3 (es) | Derivados de 1,3-dihidro-isoindol | |
| HRP20180527T1 (hr) | Modulatori receptora sfingozin 1-fosfata i postupci kiralne sintheze | |
| HRP20220886T1 (hr) | Pripravci i postupci za proizvodnju pirimidina i spojeva piridina s btk inhibicijskom aktivnošću | |
| AR065927A1 (es) | Derivados de 5,6-dihidro-1h-piridin-2-ona | |
| CN114787142B (zh) | 作为周期蛋白依赖性激酶9抑制剂的化合物及其应用 | |
| WO2014027053A1 (en) | Benzimidazoles for the treatment of cancer | |
| RU2014145819A (ru) | Бициклическое соединение | |
| AR087915A1 (es) | N-(3-(2-amino-6,6-difluor-4,4a,5,6,7,7a-hexahidro-ciclopenta-[e][1,3]oxazin-4-il)-fenil)-amidas como inhibidores de la bace1 | |
| WO2023239629A1 (en) | Compounds and pharmaceutical compositions that degrade cdk2 | |
| CN109661392A (zh) | 用于治疗增殖性障碍的线粒体抑制剂 | |
| ES2536980T3 (es) | Compuestos aril triazol con actividad antitumoral | |
| AR091687A1 (es) | Formas solidas de inhibidores de fosfodiesterasa tipo 5 | |
| BR112020007632A2 (pt) | composto, composição farmacêutica, método para inibir um dentre ou tanto ehmt1 quanto ehmt2, método para prevenir ou tratar um distúrbio sanguíneo, método para prevenir ou tratar um câncer e uso do composto | |
| AU2019323712A1 (en) | Aromatic molecules for use in the treatment of pathological conditions | |
| AR074314A1 (es) | Pirrolidinas, antagonistas de ep2 | |
| HRP20080097T5 (en) | Piperazine derivatives and their use as serotonin reuptake inhibitors or as neurokinin antagonists | |
| IL325120A (en) | Fatty acid binding protein (FABP) inhibitors, methods of use and methods of preparation |