KR20000075681A - 메탈로프로테아제 억제제로서의 후위 히드록사메이트 유도체 - Google Patents
메탈로프로테아제 억제제로서의 후위 히드록사메이트 유도체 Download PDFInfo
- Publication number
- KR20000075681A KR20000075681A KR1019997007747A KR19997007747A KR20000075681A KR 20000075681 A KR20000075681 A KR 20000075681A KR 1019997007747 A KR1019997007747 A KR 1019997007747A KR 19997007747 A KR19997007747 A KR 19997007747A KR 20000075681 A KR20000075681 A KR 20000075681A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- propyl
- acid
- formyl
- amide
- Prior art date
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- 239000003475 metalloproteinase inhibitor Substances 0.000 title description 2
- -1 3,3,3-trifluoro-n-propyl Chemical group 0.000 claims abstract description 448
- 150000001875 compounds Chemical class 0.000 claims abstract description 192
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 140
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 65
- 239000001257 hydrogen Substances 0.000 claims abstract description 63
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 49
- 125000005549 heteroarylene group Chemical group 0.000 claims abstract description 39
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims abstract description 24
- 102000005741 Metalloproteases Human genes 0.000 claims abstract description 23
- 108010006035 Metalloproteases Proteins 0.000 claims abstract description 23
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 22
- 239000011159 matrix material Substances 0.000 claims abstract description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 150000001408 amides Chemical class 0.000 claims description 104
- 229910005965 SO 2 Inorganic materials 0.000 claims description 75
- 229910052760 oxygen Inorganic materials 0.000 claims description 61
- 125000002947 alkylene group Chemical group 0.000 claims description 50
- 125000004450 alkenylene group Chemical group 0.000 claims description 48
- 125000004419 alkynylene group Chemical group 0.000 claims description 48
- 125000003342 alkenyl group Chemical group 0.000 claims description 47
- 125000000304 alkynyl group Chemical group 0.000 claims description 47
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 47
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 45
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 44
- 125000005724 cycloalkenylene group Chemical group 0.000 claims description 40
- 150000002148 esters Chemical class 0.000 claims description 35
- 125000000732 arylene group Chemical group 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 238000011282 treatment Methods 0.000 claims description 30
- 239000003153 chemical reaction reagent Substances 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 27
- 230000005764 inhibitory process Effects 0.000 claims description 21
- 239000000651 prodrug Substances 0.000 claims description 21
- 229940002612 prodrug Drugs 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- 241000124008 Mammalia Species 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 16
- 102000018697 Membrane Proteins Human genes 0.000 claims description 11
- 108010052285 Membrane Proteins Proteins 0.000 claims description 11
- 206010027476 Metastases Diseases 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 230000003834 intracellular effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000009401 metastasis Effects 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 3
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 2
- 210000004962 mammalian cell Anatomy 0.000 claims description 2
- 230000001394 metastastic effect Effects 0.000 claims 1
- 206010061289 metastatic neoplasm Diseases 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 30
- 102000004190 Enzymes Human genes 0.000 abstract description 11
- 108090000790 Enzymes Proteins 0.000 abstract description 11
- 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 abstract description 4
- 102000002274 Matrix Metalloproteinases Human genes 0.000 abstract description 4
- 108010000684 Matrix Metalloproteinases Proteins 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 171
- 239000000203 mixture Substances 0.000 description 135
- 239000000243 solution Substances 0.000 description 130
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 121
- 238000005481 NMR spectroscopy Methods 0.000 description 119
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 101
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 91
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 87
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 87
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 84
- 235000002639 sodium chloride Nutrition 0.000 description 76
- 239000011541 reaction mixture Substances 0.000 description 72
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
- 239000003921 oil Substances 0.000 description 68
- 235000019198 oils Nutrition 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 229920006395 saturated elastomer Polymers 0.000 description 66
- 239000002904 solvent Substances 0.000 description 64
- 229910052938 sodium sulfate Inorganic materials 0.000 description 63
- 235000011152 sodium sulphate Nutrition 0.000 description 63
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 60
- 239000007787 solid Substances 0.000 description 59
- 230000002829 reductive effect Effects 0.000 description 57
- 235000019439 ethyl acetate Nutrition 0.000 description 56
- 125000001424 substituent group Chemical group 0.000 description 56
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
- 239000011780 sodium chloride Substances 0.000 description 50
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 49
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- 239000000741 silica gel Substances 0.000 description 46
- 229910002027 silica gel Inorganic materials 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 45
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 45
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 41
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 40
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 38
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 35
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 34
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 30
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 29
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 27
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- 229910052717 sulfur Inorganic materials 0.000 description 26
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 24
- 238000006467 substitution reaction Methods 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 23
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical group CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 22
- 239000002585 base Substances 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- 238000000746 purification Methods 0.000 description 21
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
- 239000012043 crude product Substances 0.000 description 20
- 239000000284 extract Substances 0.000 description 20
- 235000010265 sodium sulphite Nutrition 0.000 description 20
- JSPJUVMGUPHPQP-OLZOCXBDSA-N (2r,3s)-2-(cyclohexylmethyl)-3-[formyl(hydroxy)amino]hexanoic acid Chemical compound CCC[C@H](N(O)C=O)[C@H](C(O)=O)CC1CCCCC1 JSPJUVMGUPHPQP-OLZOCXBDSA-N 0.000 description 19
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
- 125000003545 alkoxy group Chemical group 0.000 description 19
- 229910052736 halogen Chemical group 0.000 description 19
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- 230000000694 effects Effects 0.000 description 18
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- 125000004414 alkyl thio group Chemical group 0.000 description 17
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 17
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
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- 239000003112 inhibitor Substances 0.000 description 17
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- 125000004043 oxo group Chemical group O=* 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 16
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- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 12
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- XRMDRPQOUJEAJH-ZJUUUORDSA-N (2r,3s)-3-[formyl(hydroxy)amino]-2-(2-methylpropyl)hexanoic acid Chemical compound CCC[C@H](N(O)C=O)[C@@H](CC(C)C)C(O)=O XRMDRPQOUJEAJH-ZJUUUORDSA-N 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Detergent Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US3911297P | 1997-02-26 | 1997-02-26 | |
US60/039,112 | 1997-02-26 |
Publications (1)
Publication Number | Publication Date |
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KR20000075681A true KR20000075681A (ko) | 2000-12-26 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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KR1019997007747A KR20000075681A (ko) | 1997-02-26 | 1998-02-24 | 메탈로프로테아제 억제제로서의 후위 히드록사메이트 유도체 |
Country Status (16)
Country | Link |
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EP (1) | EP1019386A1 (ja) |
JP (1) | JP2001513767A (ja) |
KR (1) | KR20000075681A (ja) |
AP (1) | AP9901631A0 (ja) |
AR (1) | AR013070A1 (ja) |
AU (1) | AU6822398A (ja) |
BR (1) | BR9807763A (ja) |
CA (1) | CA2281664A1 (ja) |
HR (1) | HRP980096A2 (ja) |
IS (1) | IS5159A (ja) |
NO (1) | NO994103L (ja) |
PE (1) | PE59199A1 (ja) |
PL (1) | PL335378A1 (ja) |
TR (1) | TR199902063T2 (ja) |
WO (1) | WO1998038179A1 (ja) |
ZA (1) | ZA981532B (ja) |
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
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US6294573B1 (en) | 1997-08-06 | 2001-09-25 | Abbott Laboratories | Reverse hydroxamate inhibitors of matrix metalloproteinases |
US6235786B1 (en) | 1997-08-06 | 2001-05-22 | Abbott Laboratories | Reverse hydroxamate inhibitors of matrix metalloproteinases |
PL194240B1 (pl) | 1998-02-07 | 2007-05-31 | British Biotech Pharm | Zastosowanie pochodnych N-formylohydroksyloaminy i amidowa pochodna N-formylohydroksyloaminy |
GB9818621D0 (en) * | 1998-08-26 | 1998-10-21 | Glaxo Group Ltd | Formamide compounds as therapeutic agents |
EP1121118A4 (en) * | 1998-08-26 | 2002-09-11 | Glaxo Group Ltd | FORMAMIDE-BASED THERAPEUTIC AGENTS |
AU5688999A (en) * | 1998-08-26 | 2000-03-21 | Glaxo Group Limited | Formamide compounds as therapeutic agents |
US6288261B1 (en) | 1998-12-18 | 2001-09-11 | Abbott Laboratories | Inhibitors of matrix metalloproteinases |
US6329550B1 (en) | 1998-12-31 | 2001-12-11 | Aventis Pharmaceuticals Inc. | Amidomalonamides useful as inhibitors of MMP of matrix metalloproteinase |
GB9918869D0 (en) * | 1999-08-10 | 1999-10-13 | British Biotech Pharm | Antibacterial agents |
JP2003081838A (ja) * | 2001-09-11 | 2003-03-19 | Rohto Pharmaceut Co Ltd | グルコサミン製剤 |
EP2319518A1 (en) | 2002-02-04 | 2011-05-11 | ALFAMA-Investigacao e Desenvolvimento de Produtos Farmaceuticos Lda. | Use of CO-releasing compounds for the manufacture of a medicament for the treatment of inflammatory diseases |
CA2515534A1 (en) * | 2003-02-11 | 2004-08-26 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions based on anticholinergics and tace-inhibitors |
EP1993583A4 (en) * | 2006-02-09 | 2010-06-23 | Burnham Inst | INHIBITORS OF MEMBRANE TYPE 1 TYPE MATRIX METALLOPROTEINASE FOR THE TREATMENT OF SUGAR DIABETES DEPENDING ON INSULIN |
JP2011517313A (ja) | 2007-12-11 | 2011-06-02 | ビアメト ファーマシューティカルズ,インク. | 金属結合部分を標的化部分と組み合わせて使用する金属酵素阻害剤 |
CA2719745C (en) | 2008-03-25 | 2016-07-05 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
ATE541832T1 (de) | 2009-04-14 | 2012-02-15 | Affectis Pharmaceuticals Ag | Neuartige p2x7r-antagonisten und ihre verwendung |
WO2012110190A1 (en) | 2011-02-17 | 2012-08-23 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
PT2699242T (pt) | 2011-04-19 | 2018-01-22 | Alfama Inc | Moléculas de libertação de monóxido de carbono e utilizações das mesmas |
WO2012163792A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
WO2012163456A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
WO2013013179A1 (en) | 2011-07-21 | 2013-01-24 | Alfama, Inc. | Ruthenium carbon monoxide releasing molecules and uses thereof |
BR112021006407A8 (pt) | 2018-10-04 | 2022-12-06 | Inst Nat Sante Rech Med | uso de inibidores do egfr para ceratodermas |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
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GB9223904D0 (en) * | 1992-11-13 | 1993-01-06 | British Bio Technology | Inhibition of cytokine production |
US6037472A (en) * | 1993-11-04 | 2000-03-14 | Syntex (U.S.A.) Inc. | Matrix metalloprotease inhibitors |
EP0740652B1 (en) * | 1994-01-20 | 1998-05-06 | British Biotech Pharmaceuticals Limited | Metalloproteinase inhibitors |
GB9514867D0 (en) * | 1995-07-20 | 1995-09-20 | British Biotech Pharm | Metalloproteinase inhibitors |
HUP9903863A3 (en) * | 1995-11-23 | 2000-11-28 | British Biotech Pharm | Metalloproteinase inhibitors |
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1998
- 1998-02-24 ZA ZA9801532A patent/ZA981532B/xx unknown
- 1998-02-24 WO PCT/EP1998/001015 patent/WO1998038179A1/en not_active Application Discontinuation
- 1998-02-24 PL PL98335378A patent/PL335378A1/xx unknown
- 1998-02-24 AU AU68223/98A patent/AU6822398A/en not_active Abandoned
- 1998-02-24 JP JP53728498A patent/JP2001513767A/ja active Pending
- 1998-02-24 HR HR60/039,112A patent/HRP980096A2/hr not_active Application Discontinuation
- 1998-02-24 CA CA002281664A patent/CA2281664A1/en not_active Abandoned
- 1998-02-24 BR BR9807763-5A patent/BR9807763A/pt not_active Application Discontinuation
- 1998-02-24 KR KR1019997007747A patent/KR20000075681A/ko not_active Application Discontinuation
- 1998-02-24 AP APAP/P/1999/001631A patent/AP9901631A0/en unknown
- 1998-02-24 EP EP98913575A patent/EP1019386A1/en not_active Withdrawn
- 1998-02-24 TR TR1999/02063T patent/TR199902063T2/xx unknown
- 1998-02-25 PE PE1998000138A patent/PE59199A1/es not_active Application Discontinuation
- 1998-02-25 AR ARP980100842A patent/AR013070A1/es unknown
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1999
- 1999-08-20 IS IS5159A patent/IS5159A/is unknown
- 1999-08-25 NO NO994103A patent/NO994103L/no unknown
Also Published As
Publication number | Publication date |
---|---|
NO994103D0 (no) | 1999-08-25 |
NO994103L (no) | 1999-10-25 |
PL335378A1 (en) | 2000-04-25 |
EP1019386A1 (en) | 2000-07-19 |
AR013070A1 (es) | 2000-12-13 |
PE59199A1 (es) | 1999-06-24 |
WO1998038179A1 (en) | 1998-09-03 |
ZA981532B (en) | 1999-08-24 |
CA2281664A1 (en) | 1998-09-03 |
TR199902063T2 (xx) | 1999-12-21 |
JP2001513767A (ja) | 2001-09-04 |
IS5159A (is) | 1999-08-20 |
HRP980096A2 (en) | 1998-12-31 |
AU6822398A (en) | 1998-09-18 |
BR9807763A (pt) | 2000-02-22 |
AP9901631A0 (en) | 1999-09-30 |
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