JP2005509003A - タンパク質キナーゼインヒビターとして有用なベンゾイミダゾール化合物 - Google Patents
タンパク質キナーゼインヒビターとして有用なベンゾイミダゾール化合物 Download PDFInfo
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- JP2005509003A JP2005509003A JP2003543595A JP2003543595A JP2005509003A JP 2005509003 A JP2005509003 A JP 2005509003A JP 2003543595 A JP2003543595 A JP 2003543595A JP 2003543595 A JP2003543595 A JP 2003543595A JP 2005509003 A JP2005509003 A JP 2005509003A
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- Prior art keywords
- alkyl
- heteroaryl
- compound
- phenyl
- amino
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- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title abstract 2
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title 1
- 239000003909 protein kinase inhibitor Substances 0.000 title 1
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- 238000000034 method Methods 0.000 claims abstract description 33
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- 201000010099 disease Diseases 0.000 claims abstract description 10
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 208000026278 immune system disease Diseases 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 125
- 125000001072 heteroaryl group Chemical group 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- -1 sulfonylamino, aminosulfonyl Chemical group 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 24
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
- 125000001544 thienyl group Chemical group 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 125000002541 furyl group Chemical group 0.000 claims description 17
- 125000002252 acyl group Chemical group 0.000 claims description 16
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000002883 imidazolyl group Chemical group 0.000 claims description 13
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 13
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000002971 oxazolyl group Chemical group 0.000 claims description 12
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 10
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
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- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 150000002825 nitriles Chemical class 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 7
- JWYUFVNJZUSCSM-UHFFFAOYSA-N 2-aminobenzimidazole Chemical compound C1=CC=C2NC(N)=NC2=C1 JWYUFVNJZUSCSM-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 6
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004442 acylamino group Chemical group 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000004069 aziridinyl group Chemical group 0.000 claims description 5
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 125000004276 dioxalanyl group Chemical group 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
- 229960005486 vaccine Drugs 0.000 claims description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
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- 150000002148 esters Chemical class 0.000 claims description 4
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- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 206010010741 Conjunctivitis Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 201000004624 Dermatitis Diseases 0.000 claims description 2
- 206010012442 Dermatitis contact Diseases 0.000 claims description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 2
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 2
- 150000001266 acyl halides Chemical class 0.000 claims description 2
- 201000010105 allergic rhinitis Diseases 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001246 bromo group Chemical class Br* 0.000 claims description 2
- 206010006451 bronchitis Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 150000003857 carboxamides Chemical class 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
- 125000001309 chloro group Chemical class Cl* 0.000 claims description 2
- 208000037976 chronic inflammation Diseases 0.000 claims description 2
- 230000006020 chronic inflammation Effects 0.000 claims description 2
- 238000011260 co-administration Methods 0.000 claims description 2
- 208000010247 contact dermatitis Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001153 fluoro group Chemical class F* 0.000 claims description 2
- 208000024908 graft versus host disease Diseases 0.000 claims description 2
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims 2
- OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 claims 1
- 208000000059 Dyspnea Diseases 0.000 claims 1
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- 239000000126 substance Substances 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 239000011347 resin Substances 0.000 description 27
- 229920005989 resin Polymers 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- 210000001744 T-lymphocyte Anatomy 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
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- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
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- 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
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- 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
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- 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
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- 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
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| PCT/US2002/035494 WO2003041708A1 (en) | 2001-11-09 | 2002-11-05 | Benzimidazoles useful as protein kinase inhibitors |
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| JP2005509003A true JP2005509003A (ja) | 2005-04-07 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015518894A (ja) * | 2012-06-06 | 2015-07-06 | アイアールエム・リミテッド・ライアビリティ・カンパニーＩｒｍ，Ｌｌｃ | Ｅｇｆｒ活性を調節するための化合物および組成物 |
| JP2015526520A (ja) * | 2012-08-31 | 2015-09-10 | プリンシピア バイオファーマ インコーポレイテッド | Ｉｔｋ阻害剤としてのベンズイミダゾール誘導体 |
| JP2019510802A (ja) * | 2016-04-07 | 2019-04-18 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | タンパク質調節物質として有用な複素環アミド |
| JP2022528562A (ja) * | 2019-04-05 | 2022-06-14 | ストーム・セラピューティクス・リミテッド | Ｍｅｔｔｌ３阻害化合物 |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
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| FR2833948B1 (fr) * | 2001-12-21 | 2004-02-06 | Sod Conseils Rech Applic | Nouveaux derives de benzimidazole et leur utilisation en tant que medicament |
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-
2002
- 2002-11-05 YU YU37904A patent/YU37904A/sh unknown
- 2002-11-05 HR HR20040416A patent/HRP20040416A2/hr not_active Application Discontinuation
- 2002-11-05 IL IL16151602A patent/IL161516A0/xx unknown
- 2002-11-05 JP JP2003543595A patent/JP2005509003A/ja active Pending
- 2002-11-05 US US10/288,362 patent/US6825219B2/en not_active Expired - Lifetime
- 2002-11-05 EP EP02789445A patent/EP1448199A1/en not_active Withdrawn
- 2002-11-05 MX MXPA04004301A patent/MXPA04004301A/es unknown
- 2002-11-05 WO PCT/US2002/035494 patent/WO2003041708A1/en not_active Ceased
- 2002-11-05 PL PL02369771A patent/PL369771A1/xx not_active Application Discontinuation
- 2002-11-05 NZ NZ533310A patent/NZ533310A/xx unknown
- 2002-11-05 BR BR0214019-5A patent/BR0214019A/pt not_active Application Discontinuation
- 2002-11-05 EA EA200400595A patent/EA200400595A1/ru unknown
- 2002-11-05 CA CA002464419A patent/CA2464419A1/en not_active Abandoned
- 2002-11-05 CN CNA028270002A patent/CN1612733A/zh active Pending
- 2002-11-05 KR KR10-2004-7007023A patent/KR20040063144A/ko not_active Withdrawn
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2004
- 2004-04-19 ZA ZA200402947A patent/ZA200402947B/en unknown
- 2004-05-07 NO NO20041887A patent/NO20041887L/no unknown
- 2004-06-01 CO CO04051014A patent/CO5580788A2/es not_active Application Discontinuation
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015518894A (ja) * | 2012-06-06 | 2015-07-06 | アイアールエム・リミテッド・ライアビリティ・カンパニーＩｒｍ，Ｌｌｃ | Ｅｇｆｒ活性を調節するための化合物および組成物 |
| JP2015526520A (ja) * | 2012-08-31 | 2015-09-10 | プリンシピア バイオファーマ インコーポレイテッド | Ｉｔｋ阻害剤としてのベンズイミダゾール誘導体 |
| US9573958B2 (en) | 2012-08-31 | 2017-02-21 | Principia Biopharma, Inc. | Benzimidazole derivatives as ITK inhibitors |
| JP2019510802A (ja) * | 2016-04-07 | 2019-04-18 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | タンパク質調節物質として有用な複素環アミド |
| JP2022528562A (ja) * | 2019-04-05 | 2022-06-14 | ストーム・セラピューティクス・リミテッド | Ｍｅｔｔｌ３阻害化合物 |
| JP7762957B2 (ja) | 2019-04-05 | 2025-10-31 | ストーム・セラピューティクス・リミテッド | Ｍｅｔｔｌ３阻害化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20030144281A1 (en) | 2003-07-31 |
| CN1612733A (zh) | 2005-05-04 |
| ZA200402947B (en) | 2005-01-24 |
| WO2003041708A1 (en) | 2003-05-22 |
| CA2464419A1 (en) | 2003-05-22 |
| MXPA04004301A (es) | 2004-08-11 |
| EP1448199A1 (en) | 2004-08-25 |
| US6825219B2 (en) | 2004-11-30 |
| KR20040063144A (ko) | 2004-07-12 |
| HRP20040416A2 (en) | 2005-04-30 |
| BR0214019A (pt) | 2004-10-13 |
| CO5580788A2 (es) | 2005-11-30 |
| NO20041887L (no) | 2004-05-07 |
| PL369771A1 (en) | 2005-05-02 |
| NZ533310A (en) | 2004-12-24 |
| EA200400595A1 (ru) | 2004-10-28 |
| YU37904A (sh) | 2006-08-17 |
| IL161516A0 (en) | 2004-09-27 |
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