ES2234103T3 - Compuestos de acido tioarilsulfonamidohidroxamico. - Google Patents
Compuestos de acido tioarilsulfonamidohidroxamico.Info
- Publication number
- ES2234103T3 ES2234103T3 ES98911479T ES98911479T ES2234103T3 ES 2234103 T3 ES2234103 T3 ES 2234103T3 ES 98911479 T ES98911479 T ES 98911479T ES 98911479 T ES98911479 T ES 98911479T ES 2234103 T3 ES2234103 T3 ES 2234103T3
- Authority
- ES
- Spain
- Prior art keywords
- atoms
- carbon
- alkyl
- alkoxy
- carbon atoms
- 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.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 139
- 239000002253 acid Substances 0.000 title abstract description 65
- 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 title abstract description 13
- 102000005741 Metalloproteases Human genes 0.000 claims abstract description 20
- 108010006035 Metalloproteases Proteins 0.000 claims abstract description 20
- 230000001575 pathological effect Effects 0.000 claims abstract description 17
- 239000011159 matrix material Substances 0.000 claims abstract description 8
- 125000004429 atom Chemical group 0.000 claims description 423
- 229910052799 carbon Inorganic materials 0.000 claims description 423
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 421
- 125000004432 carbon atom Chemical group C* 0.000 claims description 370
- -1 hydride group Chemical group 0.000 claims description 164
- 125000000217 alkyl group Chemical group 0.000 claims description 118
- 229910052757 nitrogen Inorganic materials 0.000 claims description 84
- 125000003545 alkoxy group Chemical group 0.000 claims description 82
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 81
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 81
- 125000001424 substituent group Chemical group 0.000 claims description 73
- 125000003118 aryl group Chemical group 0.000 claims description 67
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
- 125000001072 heteroaryl group Chemical group 0.000 claims description 63
- 150000003839 salts Chemical class 0.000 claims description 45
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 27
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 27
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 19
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 19
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 17
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 16
- 150000004678 hydrides Chemical class 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 13
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 11
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 11
- 150000003573 thiols Chemical class 0.000 claims description 11
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 125000001769 aryl amino group Chemical group 0.000 claims description 8
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 8
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 8
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 8
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
- 125000005419 heteroarylsulfonylamino group Chemical group 0.000 claims description 8
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 8
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 8
- 125000004476 heterocycloamino group Chemical group 0.000 claims description 8
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 150000003462 sulfoxides Chemical class 0.000 claims description 8
- 150000003457 sulfones Chemical class 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 125000004470 heterocyclooxy group Chemical group 0.000 claims description 4
- 125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 39
- 230000000694 effects Effects 0.000 abstract description 21
- 102000002274 Matrix Metalloproteinases Human genes 0.000 abstract description 19
- 108010000684 Matrix Metalloproteinases Proteins 0.000 abstract description 19
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- 229940124530 sulfonamide Drugs 0.000 abstract description 4
- 150000003456 sulfonamides Chemical class 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 139
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 66
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 239000000203 mixture Substances 0.000 description 54
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- 235000019439 ethyl acetate Nutrition 0.000 description 47
- 239000007787 solid Substances 0.000 description 42
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- 238000006243 chemical reaction Methods 0.000 description 37
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 36
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 33
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 32
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 29
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 29
- 230000005764 inhibitory process Effects 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 150000002148 esters Chemical class 0.000 description 24
- 239000012267 brine Substances 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- 239000002904 solvent Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 238000004458 analytical method Methods 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 239000003112 inhibitor Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000004471 Glycine Substances 0.000 description 18
- 239000003814 drug Substances 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- 239000002585 base Substances 0.000 description 16
- 201000010099 disease Diseases 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 150000007513 acids Chemical class 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- 235000001014 amino acid Nutrition 0.000 description 13
- 229940024606 amino acid Drugs 0.000 description 13
- 150000001413 amino acids Chemical class 0.000 description 13
- 125000004494 ethyl ester group Chemical group 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 12
- 108050005238 Collagenase 3 Proteins 0.000 description 12
- 102100027995 Collagenase 3 Human genes 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 235000011181 potassium carbonates Nutrition 0.000 description 12
- 150000001408 amides Chemical class 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- VNRQLAGSSZUTTO-SNVBAGLBSA-N (2r)-2-[(4-fluorophenyl)sulfonylamino]-3-methylbutanoic acid Chemical compound CC(C)[C@H](C(O)=O)NS(=O)(=O)C1=CC=C(F)C=C1 VNRQLAGSSZUTTO-SNVBAGLBSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 9
- 125000003277 amino group Chemical group 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 9
- UGHADFWWOYTAHJ-GOSISDBHSA-N (2r)-2-[[4-(4-methylphenyl)sulfanylphenyl]sulfonyl-(2-morpholin-4-ylethyl)amino]propanoic acid Chemical compound C=1C=C(SC=2C=CC(C)=CC=2)C=CC=1S(=O)(=O)N([C@H](C)C(O)=O)CCN1CCOCC1 UGHADFWWOYTAHJ-GOSISDBHSA-N 0.000 description 8
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 8
- 102000029816 Collagenase Human genes 0.000 description 8
- 108060005980 Collagenase Proteins 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 210000002808 connective tissue Anatomy 0.000 description 8
- 229910052751 metal Inorganic materials 0.000 description 8
- 239000002184 metal Substances 0.000 description 8
- 150000004702 methyl esters Chemical class 0.000 description 8
- NLXXVSKHVGDQAT-UHFFFAOYSA-N o-(oxan-2-yl)hydroxylamine Chemical compound NOC1CCCCO1 NLXXVSKHVGDQAT-UHFFFAOYSA-N 0.000 description 8
- 230000003287 optical effect Effects 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 229960002424 collagenase Drugs 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 229910052736 halogen Inorganic materials 0.000 description 7
- 150000002367 halogens Chemical class 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- 239000011591 potassium Substances 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 102000003390 tumor necrosis factor Human genes 0.000 description 7
- IOZURBZWKJWBRL-GFCCVEGCSA-N (2r)-2-[[4-(4-methylphenyl)sulfanylphenyl]sulfonylamino]propanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@H](C)C(O)=O)=CC=C1SC1=CC=C(C)C=C1 IOZURBZWKJWBRL-GFCCVEGCSA-N 0.000 description 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 102100030416 Stromelysin-1 Human genes 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 6
- 230000033115 angiogenesis Effects 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- JOYNOYIEQOCUEJ-ZCFIWIBFSA-N (2r)-2-[(4-fluorophenyl)sulfonylamino]propanoic acid Chemical compound OC(=O)[C@@H](C)NS(=O)(=O)C1=CC=C(F)C=C1 JOYNOYIEQOCUEJ-ZCFIWIBFSA-N 0.000 description 5
- FHSAYLWMKKQZIR-QGZVFWFLSA-N (2r)-2-[2-morpholin-4-ylethyl-(4-phenylsulfanylphenyl)sulfonylamino]propanoic acid Chemical compound C=1C=C(SC=2C=CC=CC=2)C=CC=1S(=O)(=O)N([C@H](C)C(O)=O)CCN1CCOCC1 FHSAYLWMKKQZIR-QGZVFWFLSA-N 0.000 description 5
- LRKNYEWLLFHMNX-JOCHJYFZSA-N (2r)-3-methyl-2-[2-morpholin-4-ylethyl-(4-phenylsulfanylphenyl)sulfonylamino]butanoic acid Chemical compound C=1C=C(SC=2C=CC=CC=2)C=CC=1S(=O)(=O)N([C@H](C(C)C)C(O)=O)CCN1CCOCC1 LRKNYEWLLFHMNX-JOCHJYFZSA-N 0.000 description 5
- TZSLNQAAOSYMAX-HSZRJFAPSA-N (2r)-3-methyl-2-[[4-(4-methylphenyl)sulfanylphenyl]sulfonyl-(2-morpholin-4-ylethyl)amino]butanoic acid Chemical compound C=1C=C(SC=2C=CC(C)=CC=2)C=CC=1S(=O)(=O)N([C@H](C(C)C)C(O)=O)CCN1CCOCC1 TZSLNQAAOSYMAX-HSZRJFAPSA-N 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
- NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
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Classifications
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- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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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- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/42—Radicals substituted by singly-bound nitrogen atoms having hetero atoms attached to the substituent nitrogen atom
-
- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- 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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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3979597P | 1997-03-04 | 1997-03-04 | |
| US39795 | 1997-03-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2234103T3 true ES2234103T3 (es) | 2005-06-16 |
Family
ID=21907383
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES98911479T Expired - Lifetime ES2234103T3 (es) | 1997-03-04 | 1998-03-04 | Compuestos de acido tioarilsulfonamidohidroxamico. |
| ES98911480T Expired - Lifetime ES2236893T3 (es) | 1997-03-04 | 1998-03-04 | Compuestos de acido sulfonamida hidroxamico con anillo amidoaromatico. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES98911480T Expired - Lifetime ES2236893T3 (es) | 1997-03-04 | 1998-03-04 | Compuestos de acido sulfonamida hidroxamico con anillo amidoaromatico. |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6451791B1 (enExample) |
| EP (2) | EP0977745B1 (enExample) |
| JP (2) | JP2002513408A (enExample) |
| AT (2) | ATE283848T1 (enExample) |
| CA (2) | CA2285405A1 (enExample) |
| DE (2) | DE69828783T2 (enExample) |
| DK (2) | DK0983267T3 (enExample) |
| ES (2) | ES2234103T3 (enExample) |
| PT (1) | PT983267E (enExample) |
| WO (1) | WO1998039329A1 (enExample) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6747027B1 (en) | 1996-07-22 | 2004-06-08 | Pharmacia Corporation | Thiol sulfonamide metalloprotease inhibitors |
| US6277885B1 (en) | 1999-01-27 | 2001-08-21 | American Cyanamid Company | Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors |
| US6946473B2 (en) | 1999-01-27 | 2005-09-20 | Wyeth Holdings Corporation | Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors |
| BR0007784A (pt) | 1999-01-27 | 2002-02-05 | American Cyanamid Co | Composto, método para inibir mudanças patológicas mediadas pela enzima que converte o tnf-alfa (tace) em um mamìfero, composição farmacêutica, e, processo para preparar um composto |
| US6200996B1 (en) | 1999-01-27 | 2001-03-13 | American Cyanamid Company | Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors |
| US6762178B2 (en) | 1999-01-27 | 2004-07-13 | Wyeth Holdings Corporation | Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors |
| US6340691B1 (en) | 1999-01-27 | 2002-01-22 | American Cyanamid Company | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors |
| US6753337B2 (en) | 1999-01-27 | 2004-06-22 | Wyeth Holdings Corporation | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors |
| US6225311B1 (en) | 1999-01-27 | 2001-05-01 | American Cyanamid Company | Acetylenic α-amino acid-based sulfonamide hydroxamic acid tace inhibitors |
| US6326516B1 (en) | 1999-01-27 | 2001-12-04 | American Cyanamid Company | Acetylenic β-sulfonamido and phosphinic acid amide hydroxamic acid TACE inhibitors |
| US6313123B1 (en) | 1999-01-27 | 2001-11-06 | American Cyanamid Company | Acetylenic sulfonamide thiol tace inhibitors |
| US6800646B1 (en) | 1999-02-08 | 2004-10-05 | Pharmacia Corporation | Sulfamato hydroxamic acid metalloprotease inhibitor |
| WO2001005389A2 (en) * | 1999-07-16 | 2001-01-25 | G.D. Searle & Co. | N-sulfonylaminiacid derivatives as inhibitors of metalloprteinase |
| US6869951B1 (en) * | 1999-07-16 | 2005-03-22 | Pharmacia Corporation | Method of changing conformation of a matrix metalloproteinase |
| EP1088815A1 (en) * | 1999-09-28 | 2001-04-04 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonyl amino acid derivatives |
| HUP0203118A3 (en) * | 1999-10-14 | 2003-05-28 | Procter & Gamble | Beta disubstituted metalloprotease inhibitors, pharmaceutical compositions containing them and their use |
| US6696456B1 (en) | 1999-10-14 | 2004-02-24 | The Procter & Gamble Company | Beta disubstituted metalloprotease inhibitors |
| US6808902B1 (en) | 1999-11-12 | 2004-10-26 | Amgen Inc. | Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules |
| EP1265865A2 (en) | 2000-03-21 | 2002-12-18 | The Procter & Gamble Company | Difluorobutyric acid derivatives and their use as metalloprotease inhibitors |
| SK12842002A3 (sk) | 2000-03-21 | 2003-02-04 | The Procter And Gamble Company | Heterocyklický vedľajší reťazec obsahujúci N-substituované inhibítory metaloproteáz a farmaceutický prípravok s ich obsahom |
| AU2000265100A1 (en) * | 2000-07-12 | 2002-01-21 | G.D. Searle And Co. | N sulfonyl aminoacid derivatives as inhibitors of metalloproteinase |
| ES2706902T3 (es) | 2001-06-26 | 2019-04-01 | Amgen Inc | Anticuerpos para OPGL |
| CN1610661A (zh) | 2001-11-01 | 2005-04-27 | 惠氏控股公司 | 用作基质金属蛋白酶和tace的抑制剂的丙二烯芳基磺酰胺异羟肟酸 |
| MXPA04010555A (es) | 2002-04-25 | 2005-02-17 | Pharmacia Corp | Acidos piperidinil- y piperazinil-sulfonilmetil hidroxamicos y su uso como inhibidores de proteasa. |
| AU2003239599B8 (en) | 2002-05-29 | 2008-08-14 | Merck Sharp & Dohme Corp. | Compounds useful in the treatment of anthrax and inhibiting lethal factor |
| WO2005021489A2 (en) | 2002-12-23 | 2005-03-10 | Wyeth Holdings Corporation | Acetylenic aryl sulfonate hydroxamic acid tace and matrix metalloproteinase inhibitors |
| CA2511521C (en) | 2002-12-30 | 2012-02-07 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
| JP2007537256A (ja) | 2004-05-11 | 2007-12-20 | メルク エンド カムパニー インコーポレーテッド | N−スルホン化アミノ酸誘導体調製のためのプロセス |
| US7915267B2 (en) | 2005-10-28 | 2011-03-29 | Takeda Pharmaceutical Company Limited | Heterocyclic amide compound and use thereof |
| CN101410370B (zh) * | 2006-03-29 | 2013-06-12 | 诺瓦提斯公司 | 基于异羟肟酸酯的选择性mmp抑制剂 |
| EP2147684A1 (en) | 2008-07-22 | 2010-01-27 | Bracco Imaging S.p.A | Diagnostic Agents Selective Against Metalloproteases |
| EP2149568A1 (en) | 2008-07-22 | 2010-02-03 | Bracco Imaging S.p.A | Aryl-sulphonamidic dimers as metalloproteases inhibitors |
| US9023318B2 (en) | 2011-06-08 | 2015-05-05 | Siemens Medical Solutions Usa, Inc. | Compounds with matrix-metalloproteinase inhibitory activity and imaging agents thereof |
| CN111601805A (zh) | 2017-11-27 | 2020-08-28 | 科学和工业研究协会 | 作为选择性hdac抑制剂的吲哚(氨磺酰基)n-羟基苯甲酰胺衍生物 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4337197A (en) * | 1980-10-31 | 1982-06-29 | E. R. Squibb & Sons, Inc. | O-sulfated β-lactam hydroxamic acids and intermediates |
| US5506242A (en) | 1993-01-06 | 1996-04-09 | Ciba-Geigy Corporation | Arylsufonamido-substituted hydroxamic acids |
| US5455258A (en) * | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5552419A (en) * | 1993-01-06 | 1996-09-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5646167A (en) * | 1993-01-06 | 1997-07-08 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamix acids |
| PT766664E (pt) | 1994-06-22 | 2000-08-31 | British Biotech Pharm | Inibidores de metaloproteinases |
| GB9503749D0 (en) * | 1995-02-24 | 1995-04-12 | British Biotech Pharm | Synthesis of hydroxamic acid derivatives |
| US5863949A (en) * | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| DK0757984T3 (da) * | 1995-08-08 | 2003-03-03 | Ono Pharmaceutical Co | Hydroxamsyrederivater, der kan anvendes til inhibering af gelatinase |
| PT874830E (pt) * | 1995-12-08 | 2003-06-30 | Agouron Pharma | Inibidor de metaloproteinases composicao farmaceutica contendo este inibidor e a utilizacao farmaceutica e metodo util para a sua preparacao |
| CA2242416C (en) | 1996-01-23 | 2006-03-21 | Shionogi & Co., Ltd. | Sulfonated amino acid derivatives and metalloproteinase inhibitors containing the same |
| CN100413859C (zh) | 1996-01-23 | 2008-08-27 | 盐野义制药株式会社 | 磺化的氨基酸衍生物及含有它的金属蛋白酶抑制剂 |
| GB9715962D0 (en) | 1996-08-23 | 1997-10-01 | Zeneca Ltd | Sulfonamides |
-
1998
- 1998-03-04 ES ES98911479T patent/ES2234103T3/es not_active Expired - Lifetime
- 1998-03-04 DE DE69828783T patent/DE69828783T2/de not_active Expired - Fee Related
- 1998-03-04 US US09/230,205 patent/US6451791B1/en not_active Expired - Fee Related
- 1998-03-04 PT PT98911480T patent/PT983267E/pt unknown
- 1998-03-04 AT AT98911479T patent/ATE283848T1/de not_active IP Right Cessation
- 1998-03-04 DK DK98911480T patent/DK0983267T3/da active
- 1998-03-04 WO PCT/US1998/004299 patent/WO1998039329A1/en not_active Ceased
- 1998-03-04 DK DK98911479T patent/DK0977745T3/da active
- 1998-03-04 CA CA002285405A patent/CA2285405A1/en not_active Abandoned
- 1998-03-04 ES ES98911480T patent/ES2236893T3/es not_active Expired - Lifetime
- 1998-03-04 CA CA002282399A patent/CA2282399A1/en not_active Abandoned
- 1998-03-04 DE DE69827940T patent/DE69827940T2/de not_active Expired - Fee Related
- 1998-03-04 EP EP98911479A patent/EP0977745B1/en not_active Expired - Lifetime
- 1998-03-04 JP JP53879798A patent/JP2002513408A/ja not_active Abandoned
- 1998-03-04 JP JP53879898A patent/JP2002513409A/ja not_active Ceased
- 1998-03-04 EP EP98911480A patent/EP0983267B1/en not_active Expired - Lifetime
- 1998-03-04 AT AT98911480T patent/ATE287885T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| PT983267E (pt) | 2005-06-30 |
| EP0977745A4 (en) | 2000-05-31 |
| ATE283848T1 (de) | 2004-12-15 |
| DK0983267T3 (da) | 2005-04-18 |
| EP0977745B1 (en) | 2004-12-01 |
| JP2002513409A (ja) | 2002-05-08 |
| DE69828783T2 (de) | 2006-01-12 |
| DE69827940D1 (en) | 2005-01-05 |
| DK0977745T3 (da) | 2005-03-14 |
| DE69827940T2 (de) | 2005-06-09 |
| EP0977745A1 (en) | 2000-02-09 |
| ATE287885T1 (de) | 2005-02-15 |
| DE69828783D1 (de) | 2005-03-03 |
| JP2002513408A (ja) | 2002-05-08 |
| CA2282399A1 (en) | 1998-09-11 |
| US6451791B1 (en) | 2002-09-17 |
| EP0983267A1 (en) | 2000-03-08 |
| EP0983267B1 (en) | 2005-01-26 |
| ES2236893T3 (es) | 2005-07-16 |
| EP0983267A4 (en) | 2001-04-11 |
| CA2285405A1 (en) | 1998-09-11 |
| WO1998039329A1 (en) | 1998-09-11 |
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