CA2744714C - Amino pyrazole compound - Google Patents
Amino pyrazole compound Download PDFInfo
- Publication number
- CA2744714C CA2744714C CA2744714A CA2744714A CA2744714C CA 2744714 C CA2744714 C CA 2744714C CA 2744714 A CA2744714 A CA 2744714A CA 2744714 A CA2744714 A CA 2744714A CA 2744714 C CA2744714 C CA 2744714C
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- chloro
- pyridazin
- imidazo
- morpholinomethyl
- 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.)
- Expired - Fee Related
Links
- -1 Amino pyrazole compound Chemical class 0.000 title description 7
- 208000032839 leukemia Diseases 0.000 claims abstract description 10
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 claims abstract description 9
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 6
- 208000034578 Multiple myelomas Diseases 0.000 claims abstract description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 claims abstract description 6
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 6
- 208000005017 glioblastoma Diseases 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 56
- SQSZANZGUXWJEA-UHFFFAOYSA-N Gandotinib Chemical compound N1C(C)=CC(NC2=NN3C(CC=4C(=CC(Cl)=CC=4)F)=C(C)N=C3C(CN3CCOCC3)=C2)=N1 SQSZANZGUXWJEA-UHFFFAOYSA-N 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 31
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims description 17
- 241000124008 Mammalia Species 0.000 claims description 16
- 208000017733 acquired polycythemia vera Diseases 0.000 claims description 13
- 208000037244 polycythemia vera Diseases 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 208000032027 Essential Thrombocythemia Diseases 0.000 claims description 10
- 208000003476 primary myelofibrosis Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 7
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 7
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 7
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 6
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- ALKRJHWAAXQKJM-UHFFFAOYSA-N 3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-n-(5-methyl-1h-pyrazol-3-yl)-8-(morpholin-4-ylmethyl)imidazo[1,2-b]pyridazin-6-amine;hydrochloride Chemical compound Cl.N1C(C)=CC(NC2=NN3C(CC=4C(=CC(Cl)=CC=4)F)=C(C)N=C3C(CN3CCOCC3)=C2)=N1 ALKRJHWAAXQKJM-UHFFFAOYSA-N 0.000 claims description 4
- 208000037398 BCR-ABL1 negative atypical chronic myeloid leukemia Diseases 0.000 claims description 4
- 208000037379 Myeloid Chronic Atypical BCR-ABL Negative Leukemia Diseases 0.000 claims description 4
- 201000004892 atypical chronic myeloid leukemia Diseases 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 208000016595 therapy related acute myeloid leukemia and myelodysplastic syndrome Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
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- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 3
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 abstract description 2
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
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- 238000006243 chemical reaction Methods 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 21
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
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- 108090000394 Erythropoietin Proteins 0.000 description 6
- 102000000588 Interleukin-2 Human genes 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 229940105423 erythropoietin Drugs 0.000 description 6
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 6
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- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 6
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- GIMRDGMAHSBGHG-UHFFFAOYSA-N (4-chloro-2-fluorophenyl)-(6-chloro-2-methylimidazo[1,2-b]pyridazin-3-yl)methanone Chemical compound CC=1N=C2C=CC(Cl)=NN2C=1C(=O)C1=CC=C(Cl)C=C1F GIMRDGMAHSBGHG-UHFFFAOYSA-N 0.000 description 4
- WXZUHCAKLKTCGB-UHFFFAOYSA-N (4-chloro-2-fluorophenyl)-[6-chloro-2-methyl-8-(morpholin-4-ylmethyl)imidazo[1,2-b]pyridazin-3-yl]methanone Chemical compound C=1C(Cl)=NN2C(C(=O)C=3C(=CC(Cl)=CC=3)F)=C(C)N=C2C=1CN1CCOCC1 WXZUHCAKLKTCGB-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
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- NHXNBGBJOOYSEA-UHFFFAOYSA-N n'-(6-chloropyridazin-3-yl)-n,n-dimethylethanimidamide Chemical compound CN(C)C(C)=NC1=CC=C(Cl)N=N1 NHXNBGBJOOYSEA-UHFFFAOYSA-N 0.000 description 4
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- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 4
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- 239000012114 Alexa Fluor 647 Substances 0.000 description 3
- YCAGGFXSFQFVQL-UHFFFAOYSA-N Endothion Chemical compound COC1=COC(CSP(=O)(OC)OC)=CC1=O YCAGGFXSFQFVQL-UHFFFAOYSA-N 0.000 description 3
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- IWKLCYXLUROGIV-NTEUORMPSA-N tert-butyl n-[(e)-(4-methoxyphenyl)methylideneamino]carbamate Chemical compound COC1=CC=C(\C=N\NC(=O)OC(C)(C)C)C=C1 IWKLCYXLUROGIV-NTEUORMPSA-N 0.000 description 2
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- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12285408P | 2008-12-16 | 2008-12-16 | |
| US61/122,854 | 2008-12-16 | ||
| PCT/US2009/067056 WO2010074947A1 (en) | 2008-12-16 | 2009-12-08 | Amino pyrazole compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2744714A1 CA2744714A1 (en) | 2010-07-01 |
| CA2744714C true CA2744714C (en) | 2013-06-25 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2744714A Expired - Fee Related CA2744714C (en) | 2008-12-16 | 2009-12-08 | Amino pyrazole compound |
Country Status (38)
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|---|---|---|---|---|
| US8105633B2 (en) * | 2006-03-01 | 2012-01-31 | Spintec Engineering Gmbh | Method and apparatus for extraction of arthropod gland |
| GB2435646A (en) * | 2006-03-01 | 2007-09-05 | Spin Tec Engineering Gmbh | Apparatus and method of extraction of an arthropod gland |
| US20110121485A1 (en) * | 2006-10-30 | 2011-05-26 | Spintec Engineering Gmbh | Method and apparatus for the manufacture of a fiber |
| US9127074B2 (en) * | 2011-03-07 | 2015-09-08 | Fondazione Telethon | TFEB variants and uses thereof |
| JP6228113B2 (ja) * | 2011-06-15 | 2017-11-08 | ライフ・アンド・ブレイン・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＬＩＦＥ ＡＮＤ ＢＲＡＩＮ ＧｍｂＨ | グリア芽腫阻害化合物およびその使用 |
| EP2872161B1 (en) | 2012-06-26 | 2020-12-16 | Del Mar Pharmaceuticals | Dianhydrogalactitol for use in treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations |
| PL400213A1 (pl) | 2012-08-01 | 2014-02-03 | Celon Pharma Spólka Z Ograniczona Odpowiedzialnoscia | Pochodne imidazo[1,2-b]pirydazyno-6-aminy jako inhibitory kinazy JAK-2 |
| DK3179992T3 (da) | 2014-08-11 | 2022-07-11 | Acerta Pharma Bv | Terapeutisk kombination af en btk-inhibitor, en pd-1-inhibitor og/eller en pd-l1-inhibitor |
| DK3179991T3 (da) | 2014-08-11 | 2021-12-06 | Acerta Pharma Bv | Terapeutiske kombinationer af en btk-inhibitor og en bcl-2-inhibitor |
| WO2016024232A1 (en) | 2014-08-11 | 2016-02-18 | Acerta Pharma B.V. | Therapeutic combinations of a btk inhibitor, a pi3k inhibitor, a jak-2 inhibitor and/or a cdk 4/6 inhibitor |
| KR102611856B1 (ko) * | 2016-11-17 | 2023-12-07 | 브리스톨-마이어스 스큅 컴퍼니 | Il-12, il-23 및/또는 ifn-알파의 이미다조피리다진 조정제 |
| WO2018167283A1 (en) | 2017-03-17 | 2018-09-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the diagnosis and treatment of pancreatic ductal adenocarcinoma associated neural remodeling |
| US20200088732A1 (en) | 2017-04-13 | 2020-03-19 | INSERM (Institut National de la Santé et de la Recherche Mèdicale) | Methods for the diagnosis and treatment of pancreatic ductal adenocarcinoma |
| KR102328682B1 (ko) | 2018-08-27 | 2021-11-18 | 주식회사 대웅제약 | 신규한 헤테로사이클릭아민 유도체 및 이를 포함하는 약학 조성물 |
| WO2020092015A1 (en) | 2018-11-02 | 2020-05-07 | University Of Rochester | Therapeutic mitigation of epithelial infection |
| CN110305140B (zh) | 2019-07-30 | 2020-08-04 | 上海勋和医药科技有限公司 | 二氢吡咯并嘧啶类选择性jak2抑制剂 |
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| AP2003002825A0 (en) | 2000-12-21 | 2003-09-30 | Vertex Pharma | Pyrazole compounds useful as protein kinase inhibitors |
| JP2003137785A (ja) * | 2001-08-23 | 2003-05-14 | Takeda Chem Ind Ltd | Ｊｎｋ活性化阻害剤 |
| CN1596255A (zh) | 2001-12-21 | 2005-03-16 | 阿诺麦德股份有限公司 | 具有强效的与趋化因子受体结合的杂环化合物 |
| PL1853588T3 (pl) | 2005-02-16 | 2008-11-28 | Astrazeneca Ab | Związki chemiczne |
| SI1853602T1 (sl) | 2005-02-16 | 2010-11-30 | Astrazeneca Ab | Kemične spojine |
| AU2006265840B2 (en) * | 2005-07-01 | 2010-02-11 | Irm Llc | Pyrimidine-substituted benzimidazole derivatives as protein kinase inhibitors |
| GB0515026D0 (en) * | 2005-07-21 | 2005-08-31 | Novartis Ag | Organic compounds |
| US7776865B2 (en) * | 2005-10-06 | 2010-08-17 | Schering Corporation | Substituted pyrazolo[1,5-a]pyrimidines as protein kinase inhibitors |
| TWI333953B (en) * | 2005-10-06 | 2010-12-01 | Schering Corp | Pyrazolopyrimidines as protein kinase inhibitors |
| AU2006320580B2 (en) | 2005-11-30 | 2011-06-23 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-Met and uses thereof |
| US7989459B2 (en) * | 2006-02-17 | 2011-08-02 | Pharmacopeia, Llc | Purinones and 1H-imidazopyridinones as PKC-theta inhibitors |
| CA2663091A1 (en) | 2006-09-07 | 2008-03-13 | Biogen Idec Ma Inc. | Modulators of interleukin-1 receptor-associated kinase |
| WO2008052734A1 (en) * | 2006-10-30 | 2008-05-08 | Novartis Ag | Heterocyclic compounds as antiinflammatory agents |
| WO2008129255A1 (en) * | 2007-04-18 | 2008-10-30 | Astrazeneca Ab | 5-aminopyrazol-3-yl-3h-imidazo [4,5-b] pyridine derivatives and their use for the treatment of cancer |
| CN101679412A (zh) | 2007-05-23 | 2010-03-24 | 药典有限责任公司 | 作为PKC-θ抑制剂的嘌呤酮类和1H-咪唑并吡啶酮类 |
| WO2009062059A2 (en) | 2007-11-08 | 2009-05-14 | Pharmacopeia, Inc. | Isomeric purinones and 1h-imidazopyridinones as pkc-theta inhibitors |
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- 2009-12-01 AR ARP090104627A patent/AR074240A1/es unknown
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- 2009-12-08 WO PCT/US2009/067056 patent/WO2010074947A1/en not_active Ceased
- 2009-12-08 UA UAA201107565A patent/UA104743C2/ru unknown
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- 2009-12-08 KR KR1020117013705A patent/KR101300458B1/ko not_active Expired - Fee Related
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- 2009-12-08 JP JP2011540809A patent/JP5509217B2/ja not_active Expired - Fee Related
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- 2009-12-08 EP EP09795842A patent/EP2379557B1/en not_active Not-in-force
- 2009-12-08 HR HRP20120918AT patent/HRP20120918T1/hr unknown
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- 2009-12-08 US US12/742,302 patent/US20100286139A1/en not_active Abandoned
- 2009-12-08 CA CA2744714A patent/CA2744714C/en not_active Expired - Fee Related
- 2009-12-08 EA EA201170831A patent/EA019554B1/ru not_active IP Right Cessation
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- 2009-12-08 DK DK09795842.5T patent/DK2379557T3/da active
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2011
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