JP2002514179A - マトリックスメタロプロテイナーゼの阻害剤としてのビフェニル酪酸およびその誘導体 - Google Patents
マトリックスメタロプロテイナーゼの阻害剤としてのビフェニル酪酸およびその誘導体Info
- Publication number
- JP2002514179A JP2002514179A JP51270698A JP51270698A JP2002514179A JP 2002514179 A JP2002514179 A JP 2002514179A JP 51270698 A JP51270698 A JP 51270698A JP 51270698 A JP51270698 A JP 51270698A JP 2002514179 A JP2002514179 A JP 2002514179A
- Authority
- JP
- Japan
- Prior art keywords
- defined above
- biphenyl
- compound
- butyric acid
- chloro
- 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.)
- Abandoned
Links
- 102000002274 Matrix Metalloproteinases Human genes 0.000 title claims abstract description 19
- 108010000684 Matrix Metalloproteinases Proteins 0.000 title claims abstract description 19
- 239000003112 inhibitor Substances 0.000 title abstract description 17
- LGJWPXGDZJETQK-UHFFFAOYSA-N 4-(2-phenylphenyl)butanoic acid Chemical compound OC(=O)CCCC1=CC=CC=C1C1=CC=CC=C1 LGJWPXGDZJETQK-UHFFFAOYSA-N 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 241
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 19
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 claims abstract description 19
- 230000004054 inflammatory process Effects 0.000 claims abstract description 17
- 206010061218 Inflammation Diseases 0.000 claims abstract description 16
- 102000000424 Matrix Metalloproteinase 2 Human genes 0.000 claims abstract description 15
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 claims abstract description 15
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 15
- 230000006378 damage Effects 0.000 claims abstract description 14
- 108010016160 Matrix Metalloproteinase 3 Proteins 0.000 claims abstract description 13
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims abstract description 12
- 206010003246 arthritis Diseases 0.000 claims abstract description 12
- 230000001684 chronic effect Effects 0.000 claims abstract description 12
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 12
- 206010019280 Heart failures Diseases 0.000 claims abstract description 11
- 201000011510 cancer Diseases 0.000 claims abstract description 11
- 208000030507 AIDS Diseases 0.000 claims abstract description 9
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
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- -1 4'-bromo-2'-fluoro-biphenyl-4-yl Chemical group 0.000 claims description 113
- 238000000034 method Methods 0.000 claims description 66
- 239000000203 mixture Substances 0.000 claims description 65
- 239000002552 dosage form Substances 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 239000011737 fluorine Substances 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 239000011734 sodium Chemical class 0.000 claims description 23
- RQJMLGGTENDEFM-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(Cl)C=C1 RQJMLGGTENDEFM-UHFFFAOYSA-N 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 210000001519 tissue Anatomy 0.000 claims description 11
- 230000001154 acute effect Effects 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 208000027418 Wounds and injury Diseases 0.000 claims description 8
- JETIIFTUWCPZEG-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-4-methoxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NOC)=CC=C1C1=CC=C(Cl)C=C1 JETIIFTUWCPZEG-UHFFFAOYSA-N 0.000 claims description 7
- 208000024777 Prion disease Diseases 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 210000000265 leukocyte Anatomy 0.000 claims description 7
- 206010052428 Wound Diseases 0.000 claims description 6
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- GIMDYSWWMCJCFQ-UHFFFAOYSA-N 4-[4-(4-bromophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(Br)C=C1 GIMDYSWWMCJCFQ-UHFFFAOYSA-N 0.000 claims description 5
- RGOIQIUXYJQZDM-UHFFFAOYSA-N 4-[4-(4-cyanophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(C#N)C=C1 RGOIQIUXYJQZDM-UHFFFAOYSA-N 0.000 claims description 5
- LNLAFCRQQATZOY-UHFFFAOYSA-N 4-[4-(4-tert-butylphenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=C(C(CCC(O)=O)=NO)C=C1 LNLAFCRQQATZOY-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 5
- IQQQHYWNSVFFEI-UHFFFAOYSA-N 4-[4-(2-fluorophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=CC=C1F IQQQHYWNSVFFEI-UHFFFAOYSA-N 0.000 claims description 4
- QABVXTKJZPEANZ-UHFFFAOYSA-N 4-[4-(3,4-dichlorophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(Cl)C(Cl)=C1 QABVXTKJZPEANZ-UHFFFAOYSA-N 0.000 claims description 4
- DXPWOIWQAFPUJZ-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(F)C=C1 DXPWOIWQAFPUJZ-UHFFFAOYSA-N 0.000 claims description 4
- ZNPLPOFIVSAATJ-UHFFFAOYSA-N 4-hydroxyimino-4-[4-(4-methoxyphenyl)phenyl]butanoic acid Chemical compound C1=CC(OC)=CC=C1C1=CC=C(C(CCC(O)=O)=NO)C=C1 ZNPLPOFIVSAATJ-UHFFFAOYSA-N 0.000 claims description 4
- MFRQVOWWSKPLHD-UHFFFAOYSA-N 4-hydroxyimino-4-[4-(4-methylphenyl)phenyl]butanoic acid Chemical compound C1=CC(C)=CC=C1C1=CC=C(C(CCC(O)=O)=NO)C=C1 MFRQVOWWSKPLHD-UHFFFAOYSA-N 0.000 claims description 4
- NTPKBGKSVCBASL-UHFFFAOYSA-N 4-hydroxyimino-4-[4-[4-(trifluoromethyl)phenyl]phenyl]butanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(C(F)(F)F)C=C1 NTPKBGKSVCBASL-UHFFFAOYSA-N 0.000 claims description 4
- 238000010561 standard procedure Methods 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- IYWKVPQGIPOZMN-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-4-hydroxybutanoic acid Chemical compound C1=CC(C(CCC(O)=O)O)=CC=C1C1=CC=C(Cl)C=C1 IYWKVPQGIPOZMN-UHFFFAOYSA-N 0.000 claims description 3
- WNZCZCAJWKJJFF-UHFFFAOYSA-N 4-hydroxyimino-4-[4-(4-methylsulfanylphenyl)phenyl]butanoic acid Chemical compound C1=CC(SC)=CC=C1C1=CC=C(C(CCC(O)=O)=NO)C=C1 WNZCZCAJWKJJFF-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 230000008859 change Effects 0.000 claims description 3
- 125000004965 chloroalkyl group Chemical group 0.000 claims description 3
- 230000035876 healing Effects 0.000 claims description 3
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 claims description 3
- ZYTOBAWIRVFDJA-UHFFFAOYSA-N 4-[4-(2,4-dichlorophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(Cl)C=C1Cl ZYTOBAWIRVFDJA-UHFFFAOYSA-N 0.000 claims description 2
- SIJLYWOEHFFLGG-UHFFFAOYSA-N 4-[4-(2,4-difluorophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(F)C=C1F SIJLYWOEHFFLGG-UHFFFAOYSA-N 0.000 claims description 2
- IGXCIGJOOHSVAF-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-2,2,3,3-tetrafluoro-4-hydroxyiminobutanoic acid Chemical class C1=CC(C(=NO)C(F)(F)C(F)(F)C(O)=O)=CC=C1C1=CC=C(Cl)C=C1 IGXCIGJOOHSVAF-UHFFFAOYSA-N 0.000 claims description 2
- PGMZAQDZZPRHLE-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-2-[2-(1,3-dioxoisoindol-2-yl)ethyl]-2-fluoro-4-hydroxyiminobutanoic acid Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCC(F)(C(O)=O)CC(=NO)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 PGMZAQDZZPRHLE-UHFFFAOYSA-N 0.000 claims description 2
- YAOAAQZCOAUNAE-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-4-(dimethylhydrazinylidene)butanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NN(C)C)=CC=C1C1=CC=C(Cl)C=C1 YAOAAQZCOAUNAE-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- UIUJIQZEACWQSV-UHFFFAOYSA-N succinic semialdehyde Chemical compound OC(=O)CCC=O UIUJIQZEACWQSV-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 10
- 230000002401 inhibitory effect Effects 0.000 claims 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 3
- 210000003205 muscle Anatomy 0.000 claims 2
- ACTQLAONUVECDR-UHFFFAOYSA-N 2-[2-[4-(4-chlorophenyl)phenyl]-2-hydroxyiminoethyl]-2-fluoro-6-phenylhexanoic acid Chemical compound C=1C=C(C=2C=CC(Cl)=CC=2)C=CC=1C(=NO)CC(F)(C(O)=O)CCCCC1=CC=CC=C1 ACTQLAONUVECDR-UHFFFAOYSA-N 0.000 claims 1
- UTHIPJQXGSUBSL-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-2-[2-(1,3-dioxobenzo[f]isoindol-2-yl)ethyl]-2-fluoro-4-hydroxyiminobutanoic acid Chemical compound O=C1C2=CC3=CC=CC=C3C=C2C(=O)N1CCC(F)(C(O)=O)CC(=NO)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 UTHIPJQXGSUBSL-UHFFFAOYSA-N 0.000 claims 1
- MZZSBYJTHHTGEM-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-2-fluoro-4-hydroxyimino-3,3-dimethylbutanoic acid Chemical compound C1=CC(C(=NO)C(C)(C(F)C(O)=O)C)=CC=C1C1=CC=C(Cl)C=C1 MZZSBYJTHHTGEM-UHFFFAOYSA-N 0.000 claims 1
- JFUAQBDWRURWGZ-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-3-fluoro-4-hydroxyimino-2,2-dimethylbutanoic acid Chemical compound C1=CC(C(=NO)C(F)C(C)(C)C(O)=O)=CC=C1C1=CC=C(Cl)C=C1 JFUAQBDWRURWGZ-UHFFFAOYSA-N 0.000 claims 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 94
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- QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 25
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- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000004305 biphenyl Substances 0.000 description 10
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 10
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- C07C323/63—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- A61P9/08—Vasodilators for multiple indications
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
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- C07C255/64—Carboxylic acid nitriles containing cyano groups and nitrogen atoms further bound to other hetero atoms, other than oxygen atoms of nitro or nitroso groups, bound to the same carbon skeleton with the nitrogen atoms further bound to oxygen atoms
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- C07C59/40—Unsaturated compounds
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- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
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- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/88—Unsaturated compounds containing keto groups containing halogen
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- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
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- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
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Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2581496P | 1996-09-04 | 1996-09-04 | |
| US2713896P | 1996-10-02 | 1996-10-02 | |
| US5490597P | 1997-08-06 | 1997-08-06 | |
| US60/054,905 | 1997-08-06 | ||
| US60/027,138 | 1997-08-06 | ||
| US60/025,814 | 1997-08-06 | ||
| PCT/US1997/014852 WO1998009940A1 (en) | 1996-09-04 | 1997-08-22 | Biphenyl butyric acids and their derivatives as inhibitors of matrix metalloproteinases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002514179A true JP2002514179A (ja) | 2002-05-14 |
| JP2002514179A5 JP2002514179A5 (https=) | 2005-04-07 |
Family
ID=27362627
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51270698A Abandoned JP2002514179A (ja) | 1996-09-04 | 1997-08-22 | マトリックスメタロプロテイナーゼの阻害剤としてのビフェニル酪酸およびその誘導体 |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US6239288B1 (https=) |
| EP (1) | EP0927156A1 (https=) |
| JP (1) | JP2002514179A (https=) |
| AR (1) | AR009723A1 (https=) |
| AU (1) | AU4159197A (https=) |
| CO (1) | CO4950616A1 (https=) |
| HR (1) | HRP970475A2 (https=) |
| PE (1) | PE109498A1 (https=) |
| WO (1) | WO1998009940A1 (https=) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007506664A (ja) * | 2003-06-20 | 2007-03-22 | グラクソ グループ リミテッド | マトリックスメタロプロテイナーゼの阻害剤 |
| JP2007223968A (ja) * | 2006-02-24 | 2007-09-06 | Osaka Prefecture Univ | 光解裂性環状化合物 |
| JP2008531494A (ja) * | 2005-02-22 | 2008-08-14 | ランバクシー ラボラトリーズ リミテッド | 喘息及びそのほかの疾病の治療用のマトリクスメタロプロテイナーゼ阻害剤としての5−フェニルペンタン酸誘導体 |
| JP2010501545A (ja) * | 2006-08-22 | 2010-01-21 | ランバクシー ラボラトリーズ リミテッド | マトリックスメタロプロテイナーゼ阻害剤 |
| JP2012513472A (ja) * | 2008-12-23 | 2012-06-14 | アクイラス ファーマシューティカルズ, インコーポレイテッド | 疼痛および他の疾患の処置のための化合物および方法 |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002514179A (ja) * | 1996-09-04 | 2002-05-14 | ワーナー―ランバート・コンパニー | マトリックスメタロプロテイナーゼの阻害剤としてのビフェニル酪酸およびその誘導体 |
| CA2263886A1 (en) * | 1996-12-09 | 1998-06-18 | Warner-Lambert Company | Method for treating and preventing heart failure and ventricular dilatation |
| AU9663798A (en) | 1997-10-06 | 1999-04-27 | Warner-Lambert Company | Heteroaryl butyric acids and their derivatives as inhibitors of matrix metalloproteinases |
| US6169103B1 (en) | 1998-03-03 | 2001-01-02 | Warner-Lambert | Fluorine-substituted biphenyl butyric acids and their derivatives as inhibitors of matrix metalloproteinases |
| KR20010101325A (ko) | 1998-12-30 | 2001-11-14 | 빌프리더 하이더 | 치환된 4-비아릴부티르산 유도체 및 5-비아릴펜탄산유도체의 호흡기 질환 치료용 매트릭스 메탈로프로테아제저해제로서의 용도 |
| EP1031349A1 (en) * | 1999-02-25 | 2000-08-30 | Bayer Aktiengesellschaft | Use of substituted 4-biarylbutyric and 5-biarylpentanoic acid derivatives for the treatment of cerebral diseases |
| US7141607B1 (en) | 2000-03-10 | 2006-11-28 | Insite Vision Incorporated | Methods and compositions for treating and inhibiting retinal neovascularization |
| EP1265864A1 (en) * | 2000-03-21 | 2002-12-18 | The Procter & Gamble Company | Heterocyclic side chain containing, n-substituted metalloprotease inhibitors |
| IL151250A0 (en) * | 2000-03-21 | 2003-04-10 | Procter & Gamble | Difluorobutyric acid metalloprotease inhibitors |
| PL357275A1 (en) * | 2000-03-21 | 2004-07-26 | The Procter & Gamble Company | Carbocyclic side chain containing metalloprotease inhibitors |
| CN1366518A (zh) * | 2000-04-25 | 2002-08-28 | 三星电子株式会社 | 作为基质金属蛋白酶抑制剂的联苯基丁酸衍生物 |
| KR100405914B1 (ko) * | 2000-04-25 | 2003-11-15 | 삼성전자주식회사 | 메트릭스 메탈로프로테이나제의 저해제로서의 비페닐부티릭산 유도체 |
| KR100405913B1 (ko) * | 2000-04-25 | 2003-11-14 | 삼성전자주식회사 | 메트릭스 메탈로프로테이나제의 저해제로서의 비페닐부티릭산 유도체 |
| DE10047118A1 (de) * | 2000-09-22 | 2002-04-11 | Bayer Ag | Verfahren zur Herstellung von Ketocarbonsäurederivaten |
| DE10113604A1 (de) * | 2001-03-20 | 2002-10-24 | Ibfb Gmbh Privates Inst Fuer B | Verfahren zur Spaltung des humanen Wachstumshormons GH |
| WO2003006006A1 (en) * | 2001-07-09 | 2003-01-23 | The Regents Of The University Of California | Use of matrix metalloproteinase inhibitors to mitigate nerve damage |
| CN1289469C (zh) * | 2001-12-20 | 2006-12-13 | 布里斯托尔-迈尔斯斯奎布公司 | α-(N-磺酰氨基)乙酰胺衍生物作为β-淀粉样蛋白抑制剂 |
| AU2003280130B2 (en) | 2002-06-28 | 2009-06-11 | Centocor, Inc. | Mammalian CH1 deleted mimetibodies, compositions, methods and uses |
| US6734579B1 (en) * | 2002-07-24 | 2004-05-11 | Apple Computer, Inc. | System and method for activating a first device from a second device |
| EP2181704B1 (en) | 2002-12-30 | 2015-05-06 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
| GB0312654D0 (en) | 2003-06-03 | 2003-07-09 | Glaxo Group Ltd | Therapeutically useful compounds |
| RU2007129149A (ru) * | 2004-12-31 | 2009-02-10 | Авентис Фармасьютикалз Инк. (Us) | Использование ряда бифенильных соединений для защиты нейронов и олигодендроцитов при лечении рассеянного склероза (рс) |
| US7319152B2 (en) | 2005-09-19 | 2008-01-15 | Wyeth | 5-Aryl-indan-1-one and analogs useful as progesterone receptor modulators |
| US7414142B2 (en) | 2005-09-19 | 2008-08-19 | Wyeth | 5-aryl-indan-1-one oximes and analogs useful as progesterone receptor modulators |
| US20110230428A1 (en) * | 2008-07-22 | 2011-09-22 | John Wityak | Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
| EP2435402B1 (en) | 2009-05-28 | 2016-04-13 | Novartis AG | Substituted aminobutyric derivatives as neprilysin inhibitors |
| CN103896796B (zh) | 2009-05-28 | 2016-04-27 | 诺华股份有限公司 | 作为脑啡肽酶抑制剂的取代的氨基丙酸衍生物 |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| MX2014002459A (es) | 2011-08-30 | 2014-04-10 | Chdi Foundation Inc | Inhibidores de quinurenina-3-monooxigenasa, composiciones farmaceuticas y metodos de uso de los mismos. |
| SI2750677T1 (sl) | 2011-08-30 | 2017-10-30 | Chdi Foundation, Inc. | Inhibitorji kinurenin-3-monooksigenaze, farmacevtski sestavki in postopki njihove uporabe |
| EP2926808A1 (en) | 2012-11-28 | 2015-10-07 | Administración General De La Communidad Autónoma De Euskadi | Use of metalloprotease inhibitors for the treatment of polycystic liver diseases |
| CU24330B1 (es) | 2013-02-14 | 2018-03-13 | Novartis Ag | Derivados del ácido 4-((1,1) bifenil-4-il)-3-(3-fosfonopropanamido) butanoico, activos como inhibidores de nep (endopeptidasa neutral) |
| US9102635B2 (en) | 2013-02-14 | 2015-08-11 | Novartis Ag | Substituted bisphenyl butanoic acid derivatives as NEP inhibitors with improved in vivo efficacy |
| US20170119776A1 (en) | 2014-04-03 | 2017-05-04 | Bayer Pharma Aktiengesellschaft | Chiral 2,5-disubstituted cyclopentanecarboxylic acid derivatives and use thereof |
| US20170114049A1 (en) | 2014-04-03 | 2017-04-27 | Bayer Pharma Aktiengesellschaft | 2,5-disubstituted cyclopentane carboxylic acids for the treatment of respiratory tract diseases |
| EP3126339A1 (de) | 2014-04-03 | 2017-02-08 | Bayer Pharma Aktiengesellschaft | 2,5-disubstituierte cyclopentancarbonsäuren und ihre verwendung |
| CN106715421A (zh) | 2014-07-17 | 2017-05-24 | Chdi基金会股份有限公司 | 用于治疗hiv相关病症的方法和组合物 |
| FR3035105A1 (fr) * | 2015-04-16 | 2016-10-21 | Metabrain Res | Derives utiles dans le traitement de l'atrophie musculaire |
| CN109422644A (zh) * | 2017-09-04 | 2019-03-05 | 任洁 | 芬布芬体内代谢产物及衍生物的用途 |
| CN109422645A (zh) * | 2017-09-04 | 2019-03-05 | 任洁 | 芬布芬体内代谢产物及衍生物作为糖尿病相关靶点调节剂的用途 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3182061A (en) * | 1961-03-20 | 1965-05-04 | Warner Lambert Pharmaceutical | 5-[4-(p-hydroxyphenoxy)phenyl]-5-oxo-3-methylvaleric acid |
| US3997589A (en) * | 1971-03-17 | 1976-12-14 | Boehringer Ingelheim Gmbh | 4-(2'-Fluoro-4-biphenylylr-4-oxo-butyric acid and esters and salts thereof |
| NL7203400A (https=) * | 1971-03-17 | 1972-09-19 | ||
| BE790085A (fr) * | 1971-10-15 | 1973-04-13 | Thomae Gmbh Dr K | Nouveaux 4-(4-biphenylyl)-butanols |
| FR2524463A1 (fr) * | 1982-04-05 | 1983-10-07 | Fabre Sa Pierre | Obtention du metbufene par synthese malonique |
| US5192753A (en) * | 1991-04-23 | 1993-03-09 | Mcgeer Patrick L | Anti-rheumatoid arthritic drugs in the treatment of dementia |
| US5789434A (en) * | 1994-11-15 | 1998-08-04 | Bayer Corporation | Derivatives of substituted 4-biarylbutyric acid as matrix metalloprotease inhibitors |
| US5886022A (en) * | 1995-06-05 | 1999-03-23 | Bayer Corporation | Substituted cycloalkanecarboxylic acid derivatives as matrix metalloprotease inhibitors |
| JP2002514179A (ja) * | 1996-09-04 | 2002-05-14 | ワーナー―ランバート・コンパニー | マトリックスメタロプロテイナーゼの阻害剤としてのビフェニル酪酸およびその誘導体 |
-
1997
- 1997-08-22 JP JP51270698A patent/JP2002514179A/ja not_active Abandoned
- 1997-08-22 AU AU41591/97A patent/AU4159197A/en not_active Abandoned
- 1997-08-22 WO PCT/US1997/014852 patent/WO1998009940A1/en not_active Ceased
- 1997-08-22 EP EP97939523A patent/EP0927156A1/en not_active Withdrawn
- 1997-09-03 CO CO97051086A patent/CO4950616A1/es unknown
- 1997-09-03 PE PE1997000780A patent/PE109498A1/es not_active Application Discontinuation
- 1997-09-03 AR ARP970104004A patent/AR009723A1/es unknown
- 1997-09-04 HR HR60/054,905A patent/HRP970475A2/hr not_active Application Discontinuation
-
1999
- 1999-03-02 US US09/254,231 patent/US6239288B1/en not_active Expired - Fee Related
-
2000
- 2000-12-14 US US09/736,802 patent/US6307089B2/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007506664A (ja) * | 2003-06-20 | 2007-03-22 | グラクソ グループ リミテッド | マトリックスメタロプロテイナーゼの阻害剤 |
| JP2008531494A (ja) * | 2005-02-22 | 2008-08-14 | ランバクシー ラボラトリーズ リミテッド | 喘息及びそのほかの疾病の治療用のマトリクスメタロプロテイナーゼ阻害剤としての5−フェニルペンタン酸誘導体 |
| JP2007223968A (ja) * | 2006-02-24 | 2007-09-06 | Osaka Prefecture Univ | 光解裂性環状化合物 |
| JP2010501545A (ja) * | 2006-08-22 | 2010-01-21 | ランバクシー ラボラトリーズ リミテッド | マトリックスメタロプロテイナーゼ阻害剤 |
| JP2012513472A (ja) * | 2008-12-23 | 2012-06-14 | アクイラス ファーマシューティカルズ, インコーポレイテッド | 疼痛および他の疾患の処置のための化合物および方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| US6307089B2 (en) | 2001-10-23 |
| WO1998009940A1 (en) | 1998-03-12 |
| US20010000513A1 (en) | 2001-04-26 |
| HRP970475A2 (en) | 1998-08-31 |
| AR009723A1 (es) | 2000-05-03 |
| US6239288B1 (en) | 2001-05-29 |
| AU4159197A (en) | 1998-03-26 |
| EP0927156A1 (en) | 1999-07-07 |
| CO4950616A1 (es) | 2000-09-01 |
| PE109498A1 (es) | 1999-01-15 |
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