CA2684594C - Benzimidazoles and pharmaceutical compositions thereof for treating mycobacterium tuberculosis or francisella tulerensis infection - Google Patents
Benzimidazoles and pharmaceutical compositions thereof for treating mycobacterium tuberculosis or francisella tulerensis infection Download PDFInfo
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- CA2684594C CA2684594C CA2684594A CA2684594A CA2684594C CA 2684594 C CA2684594 C CA 2684594C CA 2684594 A CA2684594 A CA 2684594A CA 2684594 A CA2684594 A CA 2684594A CA 2684594 C CA2684594 C CA 2684594C
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- Prior art keywords
- aryl
- cycloalkyl
- alkyl
- heterocyclic
- halo
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- 241000589601 Francisella Species 0.000 title claims abstract description 9
- 241000187479 Mycobacterium tuberculosis Species 0.000 title claims abstract description 9
- 150000001556 benzimidazoles Chemical class 0.000 title description 2
- 208000015181 infectious disease Diseases 0.000 title description 2
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 125000003118 aryl group Chemical group 0.000 claims description 62
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 150000001875 compounds Chemical class 0.000 claims description 38
- -1 fused or unfused Chemical group 0.000 claims description 26
- 101100516563 Caenorhabditis elegans nhr-6 gene Chemical group 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 125000002837 carbocyclic group Chemical group 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 101100134925 Gallus gallus COR6 gene Proteins 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 abstract description 17
- 238000000034 method Methods 0.000 abstract description 16
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 abstract description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 42
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 41
- 101150041968 CDC13 gene Proteins 0.000 description 38
- 238000005160 1H NMR spectroscopy Methods 0.000 description 26
- 235000002639 sodium chloride Nutrition 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 13
- 201000008827 tuberculosis Diseases 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 6
- 239000006172 buffering agent Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
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- 239000000706 filtrate Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- RAGRTYREMCPEIV-UHFFFAOYSA-N 5-fluoro-2,4-dinitroaniline Chemical compound NC1=CC(F)=C([N+]([O-])=O)C=C1[N+]([O-])=O RAGRTYREMCPEIV-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
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- OARNSPHYTOOVPV-UHFFFAOYSA-N 2-cyclohexyl-5-n,5-n-diethyl-1h-benzimidazole-5,6-diamine Chemical compound N1C=2C=C(N)C(N(CC)CC)=CC=2N=C1C1CCCCC1 OARNSPHYTOOVPV-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 208000034784 Tularaemia Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 3
- TVCLGQCWXYISPZ-UHFFFAOYSA-N methyl n-(4-amino-3,5-dinitrophenyl)carbamate Chemical compound COC(=O)NC1=CC([N+]([O-])=O)=C(N)C([N+]([O-])=O)=C1 TVCLGQCWXYISPZ-UHFFFAOYSA-N 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 201000009671 multidrug-resistant tuberculosis Diseases 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
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- 230000003287 optical effect Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 3
- 229960001225 rifampicin Drugs 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- RZNHSEZOLFEFGB-UHFFFAOYSA-N 2-methoxybenzoyl chloride Chemical compound COC1=CC=CC=C1C(Cl)=O RZNHSEZOLFEFGB-UHFFFAOYSA-N 0.000 description 2
- LHKSSCSHWFWGPO-UHFFFAOYSA-N 3-n,3-n-diethyl-4,6-dinitrobenzene-1,3-diamine Chemical compound CCN(CC)C1=CC(N)=C([N+]([O-])=O)C=C1[N+]([O-])=O LHKSSCSHWFWGPO-UHFFFAOYSA-N 0.000 description 2
- RMVUGEPUWQMQPR-UHFFFAOYSA-N 4-amino-3,5-dinitrobenzoic acid Chemical compound NC1=C([N+]([O-])=O)C=C(C(O)=O)C=C1[N+]([O-])=O RMVUGEPUWQMQPR-UHFFFAOYSA-N 0.000 description 2
- NZPFXNAUXZOPOQ-UHFFFAOYSA-N 4-chloro-n-[2-cyclohexyl-6-(diethylamino)-3h-benzimidazol-5-yl]benzamide Chemical compound CCN(CC)C1=CC=2NC(C3CCCCC3)=NC=2C=C1NC(=O)C1=CC=C(Cl)C=C1 NZPFXNAUXZOPOQ-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
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- 125000003277 amino group Chemical group 0.000 description 2
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- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US91298007P | 2007-04-20 | 2007-04-20 | |
| US60/912,980 | 2007-04-20 | ||
| PCT/US2008/005084 WO2008130669A1 (en) | 2007-04-20 | 2008-04-21 | Benzimidazoles and pharmaceutical compositions thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2684594A1 CA2684594A1 (en) | 2008-10-30 |
| CA2684594C true CA2684594C (en) | 2015-10-06 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2684594A Active CA2684594C (en) | 2007-04-20 | 2008-04-21 | Benzimidazoles and pharmaceutical compositions thereof for treating mycobacterium tuberculosis or francisella tulerensis infection |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US8232410B2 (enExample) |
| EP (1) | EP2154966B1 (enExample) |
| JP (1) | JP5400032B2 (enExample) |
| CN (1) | CN101677553A (enExample) |
| AU (1) | AU2008242488B2 (enExample) |
| BR (1) | BRPI0810244A2 (enExample) |
| CA (1) | CA2684594C (enExample) |
| DK (1) | DK2154966T3 (enExample) |
| EA (1) | EA016726B1 (enExample) |
| ES (1) | ES2434693T3 (enExample) |
| HR (1) | HRP20131103T1 (enExample) |
| IN (1) | IN2009KN03959A (enExample) |
| MX (1) | MX2009011281A (enExample) |
| PL (1) | PL2154966T3 (enExample) |
| PT (1) | PT2154966E (enExample) |
| SI (1) | SI2154966T1 (enExample) |
| WO (1) | WO2008130669A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8232310B2 (en) | 2006-12-29 | 2012-07-31 | Georgetown University | Targeting of EWS-FLI1 as anti-tumor therapy |
| US8039502B2 (en) | 2007-07-24 | 2011-10-18 | The Ohio State University Research Foundation | Anti-infective agents against intracellular pathogens |
| US20120108823A1 (en) | 2009-04-22 | 2012-05-03 | The Ohio State University Research Foundation | Anti-francisella agents |
| CN102695546B (zh) | 2009-09-11 | 2014-09-10 | 前体生物药物股份公司 | 作为谷氨酰胺酰环化酶抑制剂的杂环衍生物 |
| WO2013116823A1 (en) * | 2012-02-02 | 2013-08-08 | The Research Foundation Of State University Of New York | Benzimidazoles and uses thereof |
| WO2013142326A1 (en) * | 2012-03-23 | 2013-09-26 | The Research Foundation Of State University Of New York | 5-carbonylamino-/(sulfonamido-) substituted benz imidazoles and use thereof treatment of tuberculosis |
| MX377618B (es) * | 2012-04-12 | 2025-03-07 | Univ Georgetown | Métodos y composiciones para el tratamiento de la familia de tumores del sarcoma de ewing. |
| CN103333170B (zh) * | 2013-06-14 | 2016-08-10 | 清华大学 | 苯并咪唑类化合物及其用途 |
| MX2016004678A (es) | 2013-10-24 | 2017-03-10 | Univ Georgetown | Composiciones para el tratamiento del cancer. |
| US9845296B2 (en) | 2013-11-22 | 2017-12-19 | The Research Foundation For The State University Of New York | Benzimidazoles and their use in the treatment of tuberculosis |
| WO2015138611A2 (en) | 2014-03-11 | 2015-09-17 | Colorado State University Research Foundation | Methods for improved in vitro-in vivo efficacy determination |
| US11279714B2 (en) * | 2014-06-20 | 2022-03-22 | Institut Pasteur Korea | Anti-infective compounds |
| EP3204376B1 (en) | 2014-10-09 | 2023-04-19 | Oncternal Therapeutics, Inc. | Indolinone compounds and uses thereof |
| EP3436434B1 (en) | 2016-03-31 | 2020-07-08 | Oncternal Therapeutics, Inc. | Indoline analogs and uses thereof |
| EP3490553B1 (en) | 2016-07-29 | 2024-08-28 | Oncternal Therapeutics, Inc. | Combination comprising an indolinone compound and its use in the treatment of lymphoma |
| CN111303092B (zh) * | 2020-04-07 | 2021-05-25 | 山东昌邑灶户盐化有限公司 | 2,4-二硝基-6-氯苯胺衍生物、合成方法及其应用 |
| CA3226162A1 (en) | 2021-07-09 | 2023-01-12 | Plexium, Inc. | Aryl compounds and pharmaceutical compositions that modulate ikzf2 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61170732A (ja) * | 1985-01-25 | 1986-08-01 | Fuji Photo Film Co Ltd | ハロゲン化銀写真感光材料 |
| US7405235B2 (en) | 2001-05-04 | 2008-07-29 | Paratek Pharmaceuticals, Inc. | Transcription factor modulating compounds and methods of use thereof |
| JP4953456B2 (ja) * | 2004-09-30 | 2012-06-13 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 選択的アンドロゲン受容体モジュレーター（ｓａｒｍ）として有用な新規なベンゾイミダゾール誘導体 |
| WO2007105023A1 (en) * | 2006-03-15 | 2007-09-20 | Csir | Modulation of phosphoryl transferase activity of glutamine synthetase |
-
2008
- 2008-04-21 CA CA2684594A patent/CA2684594C/en active Active
- 2008-04-21 PT PT87998829T patent/PT2154966E/pt unknown
- 2008-04-21 CN CN200880021064A patent/CN101677553A/zh active Pending
- 2008-04-21 PL PL08799882T patent/PL2154966T3/pl unknown
- 2008-04-21 WO PCT/US2008/005084 patent/WO2008130669A1/en not_active Ceased
- 2008-04-21 AU AU2008242488A patent/AU2008242488B2/en not_active Ceased
- 2008-04-21 US US12/596,347 patent/US8232410B2/en not_active Expired - Fee Related
- 2008-04-21 BR BRPI0810244-9A patent/BRPI0810244A2/pt not_active Application Discontinuation
- 2008-04-21 ES ES08799882T patent/ES2434693T3/es active Active
- 2008-04-21 DK DK08799882.9T patent/DK2154966T3/da active
- 2008-04-21 IN IN3959KON2009 patent/IN2009KN03959A/en unknown
- 2008-04-21 MX MX2009011281A patent/MX2009011281A/es active IP Right Grant
- 2008-04-21 HR HRP20131103AT patent/HRP20131103T1/hr unknown
- 2008-04-21 EP EP08799882.9A patent/EP2154966B1/en not_active Not-in-force
- 2008-04-21 JP JP2010504113A patent/JP5400032B2/ja not_active Expired - Fee Related
- 2008-04-21 SI SI200831097T patent/SI2154966T1/sl unknown
- 2008-04-21 EA EA200901423A patent/EA016726B1/ru not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JP5400032B2 (ja) | 2014-01-29 |
| BRPI0810244A2 (pt) | 2014-09-30 |
| JP2010524947A (ja) | 2010-07-22 |
| DK2154966T3 (da) | 2013-11-18 |
| AU2008242488A1 (en) | 2008-10-30 |
| CN101677553A (zh) | 2010-03-24 |
| HRP20131103T1 (hr) | 2013-12-20 |
| PT2154966E (pt) | 2013-11-13 |
| EA200901423A1 (ru) | 2010-06-30 |
| WO2008130669A1 (en) | 2008-10-30 |
| ES2434693T3 (es) | 2013-12-17 |
| SI2154966T1 (sl) | 2014-02-28 |
| US8232410B2 (en) | 2012-07-31 |
| EP2154966A1 (en) | 2010-02-24 |
| EP2154966A4 (en) | 2010-12-15 |
| MX2009011281A (es) | 2010-03-08 |
| EA016726B1 (ru) | 2012-07-30 |
| CA2684594A1 (en) | 2008-10-30 |
| PL2154966T3 (pl) | 2014-03-31 |
| IN2009KN03959A (enExample) | 2015-08-28 |
| AU2008242488B2 (en) | 2014-10-30 |
| EP2154966B1 (en) | 2013-08-21 |
| US20100256203A1 (en) | 2010-10-07 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request |
Effective date: 20130422 |