HRP970475A2 - Biphenyl butyric acids and their derivatives as inhibitors of matrix metalloproteinases - Google Patents
Biphenyl butyric acids and their derivatives as inhibitors of matrix metalloproteinases Download PDFInfo
- Publication number
- HRP970475A2 HRP970475A2 HR60/054,905A HRP970475A HRP970475A2 HR P970475 A2 HRP970475 A2 HR P970475A2 HR P970475 A HRP970475 A HR P970475A HR P970475 A2 HRP970475 A2 HR P970475A2
- Authority
- HR
- Croatia
- Prior art keywords
- biphenyl
- compound
- butyric acid
- hydroxyimino
- chloro
- Prior art date
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- 102000002274 Matrix Metalloproteinases Human genes 0.000 title claims description 17
- 108010000684 Matrix Metalloproteinases Proteins 0.000 title claims description 17
- 239000003112 inhibitor Substances 0.000 title description 11
- DCMAPGFQLNDBGH-UHFFFAOYSA-N 1,1'-biphenyl;butanoic acid Chemical class CCCC(O)=O.C1=CC=CC=C1C1=CC=CC=C1 DCMAPGFQLNDBGH-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 222
- -1 (±)-4-(4'-chloro-biphenyl-4-yl)-4-hydroxyimino-2-fluoro-2-(2-phenylpropyl)-butyric acid Chemical compound 0.000 claims description 94
- 238000000034 method Methods 0.000 claims description 74
- 239000000203 mixture Substances 0.000 claims description 62
- 238000002360 preparation method Methods 0.000 claims description 58
- 229910052731 fluorine Inorganic materials 0.000 claims description 29
- 239000011737 fluorine Substances 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 27
- 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 23
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 208000024827 Alzheimer disease Diseases 0.000 claims description 21
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 20
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 claims description 20
- 102000000424 Matrix Metalloproteinase 2 Human genes 0.000 claims description 18
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 claims description 18
- 230000004054 inflammatory process Effects 0.000 claims description 14
- 206010061218 Inflammation Diseases 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 206010003246 arthritis Diseases 0.000 claims description 12
- 108010016160 Matrix Metalloproteinase 3 Proteins 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 11
- 239000011734 sodium Chemical class 0.000 claims description 11
- 206010019280 Heart failures Diseases 0.000 claims description 10
- 230000001684 chronic effect Effects 0.000 claims description 10
- 201000006417 multiple sclerosis Diseases 0.000 claims description 10
- 229910052708 sodium Inorganic materials 0.000 claims description 10
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 208000006011 Stroke Diseases 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 8
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 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
- 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 7
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- ZKAXZKMSZPJJAV-UHFFFAOYSA-N 4-[4-(4-bromo-2-fluorophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(Br)C=C1F ZKAXZKMSZPJJAV-UHFFFAOYSA-N 0.000 claims description 6
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- 206010064996 Ulcerative keratitis Diseases 0.000 claims description 6
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 6
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- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 208000037803 restenosis Diseases 0.000 claims description 6
- 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 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
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- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 230000001363 autoimmune Effects 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 230000009545 invasion Effects 0.000 claims description 5
- 208000028169 periodontal disease Diseases 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
- 208000020431 spinal cord injury Diseases 0.000 claims description 5
- 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 4
- 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 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 4
- 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 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- RNOFOKVCZYVPMA-UHFFFAOYSA-N 4-[4-(4-chloro-2-fluorophenyl)phenyl]-4-hydroxyiminobutanoic acid Chemical compound C1=CC(C(CCC(O)=O)=NO)=CC=C1C1=CC=C(Cl)C=C1F RNOFOKVCZYVPMA-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 159000000007 calcium salts Chemical class 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 230000029663 wound healing Effects 0.000 claims description 3
- ONDHOCAWMCIXLR-UHFFFAOYSA-N 2-[2-[4-(4-chlorophenyl)phenyl]-2-hydroxyiminoethyl]-2-fluoro-5-phenylpentanoic acid Chemical compound C=1C=C(C=2C=CC(Cl)=CC=2)C=CC=1C(=NO)CC(F)(C(O)=O)CCCC1=CC=CC=C1 ONDHOCAWMCIXLR-UHFFFAOYSA-N 0.000 claims description 2
- LGJCTCXTISERQE-UHFFFAOYSA-N 2-[2-[4-(4-chlorophenyl)phenyl]-2-hydroxyiminoethyl]-5-(1,3-dioxoisoindol-2-yl)-2-fluoropentanoic acid Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCCC(F)(C(O)=O)CC(=NO)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 LGJCTCXTISERQE-UHFFFAOYSA-N 0.000 claims description 2
- 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
- YFSXARLZCWCFQB-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-2-fluoro-4-hydroxyimino-2-(1h-indol-3-ylmethyl)butanoic acid Chemical compound C=1NC2=CC=CC=C2C=1CC(F)(C(O)=O)CC(=NO)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 YFSXARLZCWCFQB-UHFFFAOYSA-N 0.000 claims description 2
- KTCNKNZOAIHBRD-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-2-fluoro-4-hydroxyimino-2-(phenylsulfanylmethyl)butanoic acid Chemical compound C=1C=C(C=2C=CC(Cl)=CC=2)C=CC=1C(=NO)CC(F)(C(O)=O)CSC1=CC=CC=C1 KTCNKNZOAIHBRD-UHFFFAOYSA-N 0.000 claims description 2
- QLOVCQFIZUKWFR-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-2-fluoro-4-hydroxyimino-2-methylbutanoic acid Chemical compound C1=CC(C(=NO)CC(F)(C)C(O)=O)=CC=C1C1=CC=C(Cl)C=C1 QLOVCQFIZUKWFR-UHFFFAOYSA-N 0.000 claims description 2
- IRBKJJBJLGTLKN-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-3,3-difluoro-4-hydroxyiminobutanoic acid Chemical class C1=CC(C(=NO)C(F)(F)CC(O)=O)=CC=C1C1=CC=C(Cl)C=C1 IRBKJJBJLGTLKN-UHFFFAOYSA-N 0.000 claims description 2
- JFUAQBDWRURWGZ-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-3-fluoro-4-hydroxyimino-2,2-dimethylbutanoic acid Chemical class 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 description 2
- 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 2
- 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 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 3
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 3
- 208000004210 Pressure Ulcer Diseases 0.000 claims 2
- SFJBLNTZMZBRQC-UHFFFAOYSA-N 2-[2-[4-(4-chlorophenyl)phenyl]-2-hydroxyiminoethyl]-5-(n-ethylanilino)-2-fluoro-5-oxopentanoic acid Chemical class C=1C=CC=CC=1N(CC)C(=O)CCC(F)(C(O)=O)CC(=NO)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 SFJBLNTZMZBRQC-UHFFFAOYSA-N 0.000 claims 1
- ZVQAMRMZOISPNF-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-2,2-difluoro-4-hydroxyiminobutanoic acid Chemical class C1=CC(C(CC(F)(F)C(O)=O)=NO)=CC=C1C1=CC=C(Cl)C=C1 ZVQAMRMZOISPNF-UHFFFAOYSA-N 0.000 claims 1
- MZZSBYJTHHTGEM-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)phenyl]-2-fluoro-4-hydroxyimino-3,3-dimethylbutanoic acid Chemical class 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
- 125000006239 protecting group Chemical group 0.000 claims 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 184
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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 62
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- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Inorganic materials [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 1
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- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
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- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical class [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 210000004231 tunica media Anatomy 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
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Classifications
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- C07C323/50—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
- C07C323/62—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
- 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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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- 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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- C—CHEMISTRY; METALLURGY
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- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/72—Hydrazones
- C07C251/86—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to carbon atoms of six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/63—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
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
- C07C59/56—Unsaturated compounds containing hydroxy or O-metal groups containing halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07C59/84—Unsaturated compounds containing keto groups containing six membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Immunology (AREA)
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- Molecular Biology (AREA)
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- Tropical Medicine & Parasitology (AREA)
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- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP970475A2 true HRP970475A2 (en) | 1998-08-31 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR60/054,905A HRP970475A2 (en) | 1996-09-04 | 1997-09-04 | Biphenyl butyric acids and their derivatives as inhibitors of matrix metalloproteinases |
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=) |
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| 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 |
| GB0314488D0 (en) * | 2003-06-20 | 2003-07-23 | 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) |
| CA2598518C (en) * | 2005-02-22 | 2015-04-21 | Ranbaxy Laboratories Limited | 5-phenyl-pentanoic acid derivatives as matrix metalloproteinase inhibitors for the treatment of asthma and other diseases |
| 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 |
| JP4936512B2 (ja) * | 2006-02-24 | 2012-05-23 | 公立大学法人大阪府立大学 | 光解裂性環状化合物 |
| ES2397284T3 (es) | 2006-08-22 | 2013-03-06 | Ranbaxy Laboratories Limited | Proceso para preparar inhibidores de la metaloproteinasa de la matriz y auxiliares quirales para los mismos |
| US20110230428A1 (en) * | 2008-07-22 | 2011-09-22 | John Wityak | Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
| KR101682427B1 (ko) * | 2008-12-23 | 2016-12-05 | 아쿠일루스 파마슈티컬즈, 인코포레이티드 | 통증 및 기타 질병을 치료하기 위한 화합물 및 방법 |
| 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
Also Published As
| Publication number | Publication date |
|---|---|
| US6307089B2 (en) | 2001-10-23 |
| WO1998009940A1 (en) | 1998-03-12 |
| US20010000513A1 (en) | 2001-04-26 |
| 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 |
| JP2002514179A (ja) | 2002-05-14 |
| PE109498A1 (es) | 1999-01-15 |
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