JP5766708B2 - ブロモドメイン阻害剤としてのイミダゾ［４，５−ｃ］キノリン誘導体 - Google Patents
ブロモドメイン阻害剤としてのイミダゾ［４，５−ｃ］キノリン誘導体 Download PDFInfo
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- JP5766708B2 JP5766708B2 JP2012537382A JP2012537382A JP5766708B2 JP 5766708 B2 JP5766708 B2 JP 5766708B2 JP 2012537382 A JP2012537382 A JP 2012537382A JP 2012537382 A JP2012537382 A JP 2012537382A JP 5766708 B2 JP5766708 B2 JP 5766708B2
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- Prior art keywords
- compound
- alkyl
- dimethyl
- isoxazolyl
- salt
- 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
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- 102000001805 Bromodomains Human genes 0.000 title description 32
- 108050009021 Bromodomains Proteins 0.000 title description 30
- 239000003112 inhibitor Substances 0.000 title description 18
- ITIRVXDSMXFTPW-UHFFFAOYSA-N 1H-imidazo[4,5-c]quinoline Chemical class C1=CC=CC2=C(NC=N3)C3=CN=C21 ITIRVXDSMXFTPW-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 252
- 150000003839 salts Chemical class 0.000 claims description 111
- -1 3,5-Dimethyl-4-isoxazolyl Chemical group 0.000 claims description 108
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 29
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 25
- 201000010099 disease Diseases 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 229940125763 bromodomain inhibitor Drugs 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 8
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 239000013543 active substance Substances 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 230000001363 autoimmune Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- 230000004968 inflammatory condition Effects 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical group C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 2
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 269
- 239000000543 intermediate Substances 0.000 description 139
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
- 239000000203 mixture Substances 0.000 description 133
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 117
- 235000002639 sodium chloride Nutrition 0.000 description 101
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 53
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
- 239000000843 powder Substances 0.000 description 48
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 39
- 239000012044 organic layer Substances 0.000 description 39
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 20
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
- 235000017557 sodium bicarbonate Nutrition 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 17
- 239000012043 crude product Substances 0.000 description 17
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 16
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- 235000011054 acetic acid Nutrition 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 238000010828 elution Methods 0.000 description 14
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- FLBUVOLGZFTRNG-UHFFFAOYSA-N 4-chloro-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxyquinoline-3-carboxamide Chemical compound COC1=CC2=C(Cl)C(C(N)=O)=CN=C2C=C1C=1C(C)=NOC=1C FLBUVOLGZFTRNG-UHFFFAOYSA-N 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- 150000001793 charged compounds Chemical class 0.000 description 11
- 239000002158 endotoxin Substances 0.000 description 11
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- 108010033040 Histones Proteins 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 8
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- MMIFSFKVRZRDAS-UHFFFAOYSA-N 4-(4-chloro-6-methoxy-3-nitroquinolin-7-yl)-3,5-dimethyl-1,2-oxazole Chemical compound COC1=CC2=C(Cl)C([N+]([O-])=O)=CN=C2C=C1C=1C(C)=NOC=1C MMIFSFKVRZRDAS-UHFFFAOYSA-N 0.000 description 7
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0919423.4 | 2009-11-05 | ||
| GBGB0919423.4A GB0919423D0 (en) | 2009-11-05 | 2009-11-05 | Novel compounds |
| PCT/EP2010/066699 WO2011054846A1 (en) | 2009-11-05 | 2010-11-03 | Imidazo [4, 5-c] quinoline derivates as bromodomain inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013510124A JP2013510124A (ja) | 2013-03-21 |
| JP2013510124A5 JP2013510124A5 (enExample) | 2013-11-07 |
| JP5766708B2 true JP5766708B2 (ja) | 2015-08-19 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2012537382A Expired - Fee Related JP5766708B2 (ja) | 2009-11-05 | 2010-11-03 | ブロモドメイン阻害剤としてのイミダゾ［４，５−ｃ］キノリン誘導体 |
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| US (1) | US8557984B2 (enExample) |
| EP (1) | EP2496576B1 (enExample) |
| JP (1) | JP5766708B2 (enExample) |
| ES (1) | ES2446358T3 (enExample) |
| GB (1) | GB0919423D0 (enExample) |
| WO (1) | WO2011054846A1 (enExample) |
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| ES2606958T3 (es) | 2010-05-14 | 2017-03-28 | Dana-Farber Cancer Institute, Inc. | Compuestos de tienotriazolodiazepina para tratar una neoplasia |
| CN103180318B (zh) | 2010-05-14 | 2017-05-10 | 达那-法伯癌症研究所 | 雄性避孕组合物以及使用方法 |
| CN103154246B (zh) | 2010-05-14 | 2015-11-25 | 达那-法伯癌症研究所 | 用于治疗白血病的组合物和方法 |
| US20130225524A1 (en) * | 2010-11-05 | 2013-08-29 | Deping Chai | Chemical Compounds |
| AR084070A1 (es) | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
| WO2012075456A1 (en) | 2010-12-02 | 2012-06-07 | Constellation Pharmaceuticals | Bromodomain inhibitors and uses thereof |
| AR084731A1 (es) * | 2010-12-06 | 2013-06-05 | Piramal Life Sciences Ltd | Derivados de imidazoquinolina sustituidos |
| WO2012151512A2 (en) | 2011-05-04 | 2012-11-08 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| WO2012174487A2 (en) | 2011-06-17 | 2012-12-20 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| GB201114103D0 (en) | 2011-08-17 | 2011-09-28 | Glaxosmithkline Llc | Novel compounds |
| WO2013027168A1 (en) | 2011-08-22 | 2013-02-28 | Pfizer Inc. | Novel heterocyclic compounds as bromodomain inhibitors |
| WO2013033269A1 (en) * | 2011-08-29 | 2013-03-07 | Coferon, Inc. | Bioorthogonal monomers capable of dimerizing and targeting bromodomains and methods of using same |
| CN103889986B (zh) * | 2011-09-30 | 2017-07-21 | C&C新药研究所 | 新杂环衍生物及其应用 |
| WO2013097052A1 (en) | 2011-12-30 | 2013-07-04 | Abbott Laboratories | Bromodomain inhibitors |
| WO2013155695A1 (en) | 2012-04-20 | 2013-10-24 | Abbott Laboratories | Isoindolone derivatives |
| WO2013184878A1 (en) | 2012-06-06 | 2013-12-12 | Constellation Pharmaceuticals, Inc. | Benzo [b] isoxazoloazepine bromodomain inhibitors and uses thereof |
| TWI602820B (zh) | 2012-06-06 | 2017-10-21 | 星宿藥物公司 | 溴域抑制劑及其用途 |
| HK1208681A1 (en) | 2012-06-12 | 2016-03-11 | Abbvie Inc. | Pyridinone and pyridazinone derivatives |
| EP2861255B1 (en) | 2012-06-19 | 2019-10-09 | The Broad Institute, Inc. | Diagnostic and treatment methods in subjects having or at risk of developing resistance to cancer therapy |
| US9422290B2 (en) | 2012-11-13 | 2016-08-23 | Boehringer Ingelheim International Gmbh | Triazolopyridazine |
| US9266891B2 (en) | 2012-11-16 | 2016-02-23 | Boehringer Ingelheim International Gmbh | Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| US9073878B2 (en) | 2012-11-21 | 2015-07-07 | Zenith Epigenetics Corp. | Cyclic amines as bromodomain inhibitors |
| US9765039B2 (en) | 2012-11-21 | 2017-09-19 | Zenith Epigenetics Ltd. | Biaryl derivatives as bromodomain inhibitors |
| JP2016507496A (ja) | 2012-12-21 | 2016-03-10 | ゼニス・エピジェネティクス・コーポレイションＺｅｎｉｔｈ Ｅｐｉｇｅｎｅｔｉｃｓ Ｃｏｒｐ． | ブロモドメイン阻害剤としての新規複素環式化合物 |
| WO2014128655A1 (en) * | 2013-02-25 | 2014-08-28 | Aurigene Discovery Technologies Limited | Substituted imidazo[4,5-c]quinoline derivatives as bromodomain inhibitors |
| EP2970312B1 (en) | 2013-03-11 | 2017-11-15 | The Regents of The University of Michigan | Bet bromodomain inhibitors and therapeutic methods using the same |
| WO2014159392A1 (en) | 2013-03-14 | 2014-10-02 | Dana-Farber Cancer Institute, Inc. | Bromodomain binding reagents and uses thereof |
| US9670221B2 (en) | 2013-03-14 | 2017-06-06 | Glaxosmithkline Intellectual Property (No. 2) Limited | Furopyridines as bromodomain inhibitors |
| EA201591746A1 (ru) | 2013-03-14 | 2016-08-31 | КОНВЕРДЖЕН ЭлЭлСи | Способы и композиции для ингибирования бромодомен-содержащих белков |
| WO2014152029A2 (en) * | 2013-03-15 | 2014-09-25 | Epigenetix, Inc. | Oxazolo[5,4-c]quinolin-2-one compounds as bromodomain inhibitors |
| EA035469B1 (ru) | 2013-03-15 | 2020-06-22 | Инсайт Холдингс Корпорейшн | Трициклические гетероциклы как ингибиторы белков бэт |
| US9199988B2 (en) * | 2013-03-27 | 2015-12-01 | Boehringer Ingelheim International Gmbh | Dihydroquinazolinone analogues |
| EP2978757B1 (en) | 2013-03-27 | 2017-02-08 | Boehringer Ingelheim International GmbH | Indolinone analogues as brd4 inhibitors |
| TWI530499B (zh) | 2013-03-28 | 2016-04-21 | 吉李德科學股份有限公司 | 作為溴結構域（ｂｒｏｍｏｄｏｍａｉｎ）抑制劑之苯並咪唑酮衍生物類 |
| EA027139B1 (ru) | 2013-04-26 | 2017-06-30 | Бейджин, Лтд. | Замещенные 5-(3,5-диметилизоксазол-4-ил)индолин-2-оны |
| DK2991683T3 (da) | 2013-05-02 | 2019-11-04 | Glykos Finland Oy | Konjugater af et glykoprotein eller en glykan med en toksisk ladning |
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| GB9004781D0 (en) | 1990-03-02 | 1990-04-25 | Glaxo Group Ltd | Device |
| JP2006513212A (ja) * | 2002-12-20 | 2006-04-20 | スリーエム イノベイティブ プロパティズ カンパニー | アリール／ヘタリール置換されたイミダゾキノリン |
| BRPI0416128B8 (pt) | 2003-11-03 | 2021-06-22 | Glaxo Group Ltd | dispositivo de dispensação de fluido |
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| AU2006332000A1 (en) * | 2005-12-16 | 2007-07-05 | Coley Pharmaceutical Group, Inc. | Substituted imidazoquinolines, imidazonaphthyridines, and imidazopyridines, compositions, and methods |
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| CN101910182B (zh) | 2007-12-28 | 2013-07-17 | 田边三菱制药株式会社 | 抗癌剂 |
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