JP4427328B2 - ヒト−adam−10インヒビター - Google Patents
ヒト−adam−10インヒビター Download PDFInfo
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- JP4427328B2 JP4427328B2 JP2003552713A JP2003552713A JP4427328B2 JP 4427328 B2 JP4427328 B2 JP 4427328B2 JP 2003552713 A JP2003552713 A JP 2003552713A JP 2003552713 A JP2003552713 A JP 2003552713A JP 4427328 B2 JP4427328 B2 JP 4427328B2
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- Prior art keywords
- alkyl
- alkoxy
- substituted
- group
- unsubstituted
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title claims abstract description 9
- 101000959356 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 10 Proteins 0.000 title description 13
- 102000056542 human ADAM10 Human genes 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 110
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- 206010003246 arthritis Diseases 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 104
- 150000002367 halogens Chemical class 0.000 claims description 100
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 93
- -1 C 1 -C 6 alkoxy Chemical group 0.000 claims description 84
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 70
- 229910052739 hydrogen Inorganic materials 0.000 claims description 68
- 229910052799 carbon Inorganic materials 0.000 claims description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 50
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 38
- 125000002757 morpholinyl group Chemical group 0.000 claims description 37
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 36
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- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 29
- 125000004076 pyridyl group Chemical group 0.000 claims description 29
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- 125000000168 pyrrolyl group Chemical group 0.000 claims description 27
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 24
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 20
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- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 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 4
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- 239000001301 oxygen Substances 0.000 claims description 4
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- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
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- 239000003921 oil Substances 0.000 description 14
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- 229910052717 sulfur Inorganic materials 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 13
- 125000001544 thienyl group Chemical group 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
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- 229910052794 bromium Inorganic materials 0.000 description 12
- 229910052801 chlorine Inorganic materials 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 12
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- 125000004438 haloalkoxy group Chemical group 0.000 description 11
- 125000001188 haloalkyl group Chemical group 0.000 description 11
- 230000003287 optical effect Effects 0.000 description 11
- 239000004475 Arginine Substances 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 125000003710 aryl alkyl group Chemical group 0.000 description 10
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- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 8
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
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Classifications
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34017901P | 2001-12-14 | 2001-12-14 | |
| PCT/US2002/039816 WO2003051825A1 (en) | 2001-12-14 | 2002-12-13 | Human adam-10 inhibitors |
Publications (3)
| Publication Number | Publication Date |
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| JP2005513065A JP2005513065A (ja) | 2005-05-12 |
| JP2005513065A5 JP2005513065A5 (enExample) | 2006-01-05 |
| JP4427328B2 true JP4427328B2 (ja) | 2010-03-03 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2003552713A Expired - Fee Related JP4427328B2 (ja) | 2001-12-14 | 2002-12-13 | ヒト−adam−10インヒビター |
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| Country | Link |
|---|---|
| US (2) | US7498358B2 (enExample) |
| EP (1) | EP1461313B1 (enExample) |
| JP (1) | JP4427328B2 (enExample) |
| AT (1) | ATE438618T1 (enExample) |
| AU (1) | AU2002346724B2 (enExample) |
| CA (1) | CA2473938C (enExample) |
| DE (1) | DE60233261D1 (enExample) |
| ES (1) | ES2331177T3 (enExample) |
| WO (1) | WO2003051825A1 (enExample) |
Families Citing this family (22)
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| WO2003051825A1 (en) * | 2001-12-14 | 2003-06-26 | Exelixis, Inc. | Human adam-10 inhibitors |
| AU2003239599B8 (en) | 2002-05-29 | 2008-08-14 | Merck Sharp & Dohme Corp. | Compounds useful in the treatment of anthrax and inhibiting lethal factor |
| EP2428509A1 (en) | 2002-06-12 | 2012-03-14 | Symphony Evolution, Inc. | Human adam-10 inhibitors |
| US8088737B2 (en) | 2003-04-04 | 2012-01-03 | Incyte Corporation | Compositions, methods and kits relating to Her-2 cleavage |
| GB0311228D0 (en) * | 2003-05-16 | 2003-06-18 | Celltech R&D Ltd | Assay |
| EP1493445A1 (en) * | 2003-07-04 | 2005-01-05 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibition of stress-induced ligand-dependent EGFR activation |
| US7163942B2 (en) | 2004-04-01 | 2007-01-16 | Pfizer Inc. | Sulfonamide compounds for the treatment of neurodegenerative disorders |
| JP2007537256A (ja) | 2004-05-11 | 2007-12-20 | メルク エンド カムパニー インコーポレーテッド | N−スルホン化アミノ酸誘導体調製のためのプロセス |
| EP1623995A1 (en) * | 2004-08-06 | 2006-02-08 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Inhibitors of L1 and ADAM10 for the treatment of carcinomas |
| EP1984500A2 (en) * | 2006-01-13 | 2008-10-29 | Vanderbilt University | Adam10 and its uses related to infection |
| WO2007103114A2 (en) | 2006-03-07 | 2007-09-13 | The Brigham & Women's Hospital, Inc. | Notch inhibition in the treatment or prevention of atherosclerosis |
| US9567396B2 (en) | 2006-03-07 | 2017-02-14 | Evonik Degussa Gmbh | Notch inhibition in the prevention of vein graft failure |
| JPWO2009096198A1 (ja) * | 2008-02-01 | 2011-05-26 | 一般社団法人ファルマIp | 新規ビアリール誘導体 |
| US20120129189A1 (en) * | 2009-07-17 | 2012-05-24 | Chulan Kwon | Methods of Controlling Cell Proliferation |
| EP2493497A4 (en) | 2009-11-01 | 2013-07-24 | Brigham & Womens Hospital | NOTCH INHIBITION IN THE TREATMENT AND PROPHYLAXIS OF ADIPOSITAS AND METABOLISM SYNDROME |
| EP2597084B1 (en) | 2010-07-08 | 2016-06-29 | Kaken Pharmaceutical Co., Ltd. | N-hydroxyformamide derivative and pharmaceutical containing same |
| WO2012064865A1 (en) | 2010-11-09 | 2012-05-18 | The University Of Chicago | Role of adam10 and its relevance to disease and therapeutics |
| EP2606884A1 (en) | 2011-12-21 | 2013-06-26 | Ecole Polytechnique Fédérale de Lausanne (EPFL) | Inhibitors of notch signaling pathway and use thereof in treatment of cancers |
| BR112020026148A2 (pt) | 2018-06-21 | 2021-03-16 | Cellestia Biotech Ag | Processo para fabricar éteres amino diarílicos e sais de cloridratos de éteres amino diarílicos |
| EP3823672A1 (en) | 2018-07-19 | 2021-05-26 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Combination for treating cancer |
| CN108947850B (zh) * | 2018-07-23 | 2021-05-18 | 蚌埠中实化学技术有限公司 | 一种3,4,5-三氟苯胺的制备方法 |
| EP4244391A1 (en) | 2020-11-16 | 2023-09-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for predicting and treating uveal melanoma |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5985900A (en) | 1997-04-01 | 1999-11-16 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them and their pharmaceutical uses |
| DE69836877D1 (de) | 1997-07-22 | 2007-02-22 | Shionogi & Co | Verwendung von Matrix- Metalloproteinase Inhibitoren zur Behandlung oder Vorbeugung von Glomerulopathie |
| EP1918278A1 (en) | 1998-02-04 | 2008-05-07 | Novartis AG | Sulfonylamino derivatives which inhibit matrix-degrading metalloproteinases |
| JPH11246527A (ja) | 1998-03-02 | 1999-09-14 | Shionogi & Co Ltd | Mmp−8阻害剤 |
| WO2000015213A1 (en) | 1998-09-11 | 2000-03-23 | Shionogi & Co., Ltd. | Remedal or preventive agent for congestive heart failure |
| WO2003051825A1 (en) * | 2001-12-14 | 2003-06-26 | Exelixis, Inc. | Human adam-10 inhibitors |
-
2002
- 2002-12-13 WO PCT/US2002/039816 patent/WO2003051825A1/en not_active Ceased
- 2002-12-13 DE DE60233261T patent/DE60233261D1/de not_active Expired - Lifetime
- 2002-12-13 JP JP2003552713A patent/JP4427328B2/ja not_active Expired - Fee Related
- 2002-12-13 US US10/498,338 patent/US7498358B2/en not_active Expired - Fee Related
- 2002-12-13 AU AU2002346724A patent/AU2002346724B2/en not_active Ceased
- 2002-12-13 CA CA2473938A patent/CA2473938C/en not_active Expired - Fee Related
- 2002-12-13 AT AT02784794T patent/ATE438618T1/de not_active IP Right Cessation
- 2002-12-13 ES ES02784794T patent/ES2331177T3/es not_active Expired - Lifetime
- 2002-12-13 EP EP02784794A patent/EP1461313B1/en not_active Expired - Lifetime
-
2009
- 2009-02-02 US US12/322,422 patent/US7951972B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES2331177T3 (es) | 2009-12-23 |
| ATE438618T1 (de) | 2009-08-15 |
| JP2005513065A (ja) | 2005-05-12 |
| EP1461313A1 (en) | 2004-09-29 |
| CA2473938C (en) | 2013-10-08 |
| EP1461313B1 (en) | 2009-08-05 |
| CA2473938A1 (en) | 2003-06-26 |
| AU2002346724B2 (en) | 2009-04-30 |
| AU2002346724A1 (en) | 2003-06-30 |
| EP1461313A4 (en) | 2006-03-01 |
| US7498358B2 (en) | 2009-03-03 |
| US20050227973A1 (en) | 2005-10-13 |
| DE60233261D1 (de) | 2009-09-17 |
| US7951972B2 (en) | 2011-05-31 |
| US20090143386A1 (en) | 2009-06-04 |
| WO2003051825A1 (en) | 2003-06-26 |
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