JP2004529874A - マトリックスメタロプロテイナーゼ阻害剤 - Google Patents
マトリックスメタロプロテイナーゼ阻害剤 Download PDFInfo
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- JP2004529874A JP2004529874A JP2002563877A JP2002563877A JP2004529874A JP 2004529874 A JP2004529874 A JP 2004529874A JP 2002563877 A JP2002563877 A JP 2002563877A JP 2002563877 A JP2002563877 A JP 2002563877A JP 2004529874 A JP2004529874 A JP 2004529874A
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- Prior art keywords
- compound
- hydrogen bond
- ring
- hydrophobic group
- mmp
- Prior art date
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- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title description 2
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 title description 2
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- 239000001257 hydrogen Substances 0.000 claims abstract description 104
- 125000001165 hydrophobic group Chemical group 0.000 claims abstract description 88
- 102100027995 Collagenase 3 Human genes 0.000 claims abstract description 73
- 239000002904 solvent Substances 0.000 claims abstract description 35
- 239000003446 ligand Substances 0.000 claims abstract description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
- 201000010099 disease Diseases 0.000 claims abstract description 22
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- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 12
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- 108050005238 Collagenase 3 Proteins 0.000 claims abstract 18
- 239000000370 acceptor Substances 0.000 claims description 76
- 125000004429 atom Chemical group 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 125000005842 heteroatom Chemical group 0.000 claims description 30
- 125000005647 linker group Chemical group 0.000 claims description 23
- 125000006413 ring segment Chemical group 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 17
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- 239000003112 inhibitor Substances 0.000 claims description 14
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- 125000001424 substituent group Chemical group 0.000 claims description 11
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
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- 238000006243 chemical reaction Methods 0.000 description 34
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- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 32
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- 125000000217 alkyl group Chemical group 0.000 description 25
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 19
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- 239000011734 sodium Substances 0.000 description 19
- 230000027455 binding Effects 0.000 description 18
- 229910052717 sulfur Chemical group 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 239000012043 crude product Substances 0.000 description 16
- 239000011347 resin Substances 0.000 description 16
- 229920005989 resin Polymers 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- 150000001408 amides Chemical class 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- 239000001301 oxygen Chemical group 0.000 description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 13
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- ZILSBZLQGRBMOR-UHFFFAOYSA-N 1,3-benzodioxol-5-ylmethanamine Chemical compound NCC1=CC=C2OCOC2=C1 ZILSBZLQGRBMOR-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
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- 239000004480 active ingredient Substances 0.000 description 11
- 235000010233 benzoic acid Nutrition 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
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- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 10
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- 229940095102 methyl benzoate Drugs 0.000 description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 125000003282 alkyl amino group Chemical group 0.000 description 8
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
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- FVLGJNDWJZFOHL-UHFFFAOYSA-N 3-benzyl-2,4-dioxo-1h-quinazoline-6-carboxylic acid Chemical compound O=C1C2=CC(C(=O)O)=CC=C2NC(=O)N1CC1=CC=CC=C1 FVLGJNDWJZFOHL-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
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- BZXFEKCITXZDLQ-UHFFFAOYSA-N methyl 3-benzyl-2,4-dioxo-1h-quinazoline-6-carboxylate Chemical compound O=C1C2=CC(C(=O)OC)=CC=C2NC(=O)N1CC1=CC=CC=C1 BZXFEKCITXZDLQ-UHFFFAOYSA-N 0.000 description 4
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- GSIBTIUXYYFCPU-UHFFFAOYSA-N tert-butyl 4-(bromomethyl)benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(CBr)C=C1 GSIBTIUXYYFCPU-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
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- 125000006823 (C1-C6) acyl group Chemical group 0.000 description 3
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Images
Classifications
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- 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
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007049820A1 (ja) * | 2005-10-28 | 2007-05-03 | Takeda Pharmaceutical Company Limited | 複素環アミド化合物及びその用途 |
| JPWO2006062093A1 (ja) * | 2004-12-07 | 2008-06-12 | 富山化学工業株式会社 | 新規なアントラニル酸誘導体またはその塩 |
| JP2010083795A (ja) * | 2008-09-30 | 2010-04-15 | Sun Medical Co Ltd | 酵素阻害作用または酵素阻害作用と抗菌作用とを有する歯科用組成物 |
| JP2018515559A (ja) * | 2015-05-20 | 2018-06-14 | グアンドン ジョンシェン ファーマシューティカル カンパニー リミテッド | ヒドロキシプリン類化合物及びその応用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| PA8539401A1 (es) * | 2001-02-14 | 2002-10-28 | Warner Lambert Co | Quinazolinas como inhibidores de mmp-13 |
| PA8539501A1 (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Compuestos triazolo como inhibidores de mmp |
| DOP2002000334A (es) * | 2001-02-14 | 2002-08-30 | Warner Lambert Co | Pirimidinas biciclicas como inhibidores de metaloproteinasas de matriz |
| DOP2002000328A (es) | 2001-02-14 | 2003-08-30 | Warner Lambert Co | Pirimidinas inhibidoras de metaloproteinasas de matriz |
| DOP2002000332A (es) * | 2001-02-14 | 2002-08-30 | Warner Lambert Co | Inhibidores de piridina de metaloproteinasas de la matriz |
| BR0207865A (pt) | 2001-02-14 | 2004-03-23 | Warner Lambert Co | Benzotiadiazinas inibidores de metaloproteinases de matriz |
| US20040006205A1 (en) * | 2001-04-03 | 2004-01-08 | Li Li | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
| PE20030541A1 (es) * | 2001-10-12 | 2003-08-13 | Warner Lambert Co | Compuestos pirimidina de anillo fusionado alquinilado como inhibidores de metaloproteasa de matriz tipo 13 |
| US6962922B2 (en) | 2001-10-12 | 2005-11-08 | Warner-Lambert Company Llc | Alkynylated quinazoline compounds |
| CA2462442A1 (en) | 2001-10-12 | 2003-04-24 | Warner-Lambert Company Llc | Alkyne matrix metalloproteinase inhibitors |
| AU2002249275A1 (en) * | 2002-03-08 | 2003-09-22 | Warner-Lambert Company Llc | Oxo azabicyclic compounds |
| US6894057B2 (en) | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US6747147B2 (en) | 2002-03-08 | 2004-06-08 | Warner-Lambert Company | Oxo-azabicyclic compounds |
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-
2002
- 2002-02-08 PA PA20028539301A patent/PA8539301A1/es unknown
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- 2002-02-13 MX MXPA03007250A patent/MXPA03007250A/es unknown
- 2002-02-13 WO PCT/IB2002/000447 patent/WO2002064080A2/en not_active Ceased
- 2002-02-13 BR BR0207864-3A patent/BR0207864A/pt not_active IP Right Cessation
- 2002-02-13 US US10/075,069 patent/US20030078276A1/en not_active Abandoned
- 2002-02-13 EP EP02710275A patent/EP1361873A4/en not_active Withdrawn
- 2002-02-13 PE PE2002000116A patent/PE20020873A1/es not_active Application Discontinuation
- 2002-02-13 JP JP2002563877A patent/JP2004529874A/ja not_active Abandoned
- 2002-02-13 AU AU2002228302A patent/AU2002228302A1/en not_active Abandoned
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- 2002-02-13 AR ARP020100472A patent/AR033859A1/es not_active Application Discontinuation
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPWO2006062093A1 (ja) * | 2004-12-07 | 2008-06-12 | 富山化学工業株式会社 | 新規なアントラニル酸誘導体またはその塩 |
| WO2007049820A1 (ja) * | 2005-10-28 | 2007-05-03 | Takeda Pharmaceutical Company Limited | 複素環アミド化合物及びその用途 |
| US7915267B2 (en) | 2005-10-28 | 2011-03-29 | Takeda Pharmaceutical Company Limited | Heterocyclic amide compound and use thereof |
| JP5324785B2 (ja) * | 2005-10-28 | 2013-10-23 | 武田薬品工業株式会社 | 複素環アミド化合物及びその用途 |
| JP2010083795A (ja) * | 2008-09-30 | 2010-04-15 | Sun Medical Co Ltd | 酵素阻害作用または酵素阻害作用と抗菌作用とを有する歯科用組成物 |
| JP2018515559A (ja) * | 2015-05-20 | 2018-06-14 | グアンドン ジョンシェン ファーマシューティカル カンパニー リミテッド | ヒドロキシプリン類化合物及びその応用 |
Also Published As
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|---|---|
| AR033859A1 (es) | 2004-01-07 |
| WO2002064080A3 (en) | 2002-12-12 |
| AU2002228302A1 (en) | 2002-08-28 |
| BR0207864A (pt) | 2004-03-09 |
| SV2002000874A (es) | 2002-11-29 |
| US20030078276A1 (en) | 2003-04-24 |
| EP1361873A4 (en) | 2005-10-26 |
| HN2002000037A (es) | 2002-07-09 |
| PA8539301A1 (es) | 2002-09-30 |
| US20050004126A1 (en) | 2005-01-06 |
| CA2437643A1 (en) | 2002-08-22 |
| EP1361873A2 (en) | 2003-11-19 |
| WO2002064080A2 (en) | 2002-08-22 |
| MXPA03007250A (es) | 2005-07-25 |
| UY27174A1 (es) | 2002-09-30 |
| PE20020873A1 (es) | 2002-10-26 |
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