JP2001516338A - マトリックスメタロプロテイナーゼ・インヒビターとしてのβ―スルホニルヒドロキサム酸 - Google Patents
マトリックスメタロプロテイナーゼ・インヒビターとしてのβ―スルホニルヒドロキサム酸Info
- Publication number
- JP2001516338A JP2001516338A JP51570298A JP51570298A JP2001516338A JP 2001516338 A JP2001516338 A JP 2001516338A JP 51570298 A JP51570298 A JP 51570298A JP 51570298 A JP51570298 A JP 51570298A JP 2001516338 A JP2001516338 A JP 2001516338A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- hydroxy
- propionamide
- alkyl
- methoxybenzenesulfonyl
- 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.)
- Withdrawn
Links
- 239000002253 acid Substances 0.000 title description 40
- 150000007513 acids Chemical class 0.000 title description 2
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title description 2
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 118
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 90
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims abstract description 23
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 15
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 15
- 230000008354 tissue degradation Effects 0.000 claims abstract description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 11
- KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-N 0.000 claims abstract description 5
- -1 substituted Chemical class 0.000 claims description 345
- 125000005843 halogen group Chemical group 0.000 claims description 67
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
- RHYBFKMFHLPQPH-UHFFFAOYSA-N N-methylhydantoin Chemical compound CN1CC(=O)NC1=O RHYBFKMFHLPQPH-UHFFFAOYSA-N 0.000 claims description 60
- 125000003545 alkoxy group Chemical group 0.000 claims description 43
- NOHNSECEKFOVGT-UHFFFAOYSA-N 1-butylimidazolidine-2,4-dione Chemical compound CCCCN1CC(=O)NC1=O NOHNSECEKFOVGT-UHFFFAOYSA-N 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- XIUCDTIXVLEUMG-UHFFFAOYSA-N n-hydroxy-2-[(4-methoxyphenyl)sulfonylmethyl]-3-octylsulfonylpropanamide Chemical compound CCCCCCCCS(=O)(=O)CC(C(=O)NO)CS(=O)(=O)C1=CC=C(OC)C=C1 XIUCDTIXVLEUMG-UHFFFAOYSA-N 0.000 claims description 21
- YIROYDNZEPTFOL-UHFFFAOYSA-N 5,5-Dimethylhydantoin Chemical compound CC1(C)NC(=O)NC1=O YIROYDNZEPTFOL-UHFFFAOYSA-N 0.000 claims description 19
- 201000010099 disease Diseases 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 125000006126 n-butyl sulfonyl group Chemical group 0.000 claims description 12
- 229940080818 propionamide Drugs 0.000 claims description 12
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 210000002808 connective tissue Anatomy 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 239000011593 sulfur Substances 0.000 claims description 10
- GGFLARIFGUFMLY-UHFFFAOYSA-N 3-(4-bromophenyl)sulfonyl-2-[(4-bromophenyl)sulfonylmethyl]-n-hydroxypropanamide Chemical compound C=1C=C(Br)C=CC=1S(=O)(=O)CC(C(=O)NO)CS(=O)(=O)C1=CC=C(Br)C=C1 GGFLARIFGUFMLY-UHFFFAOYSA-N 0.000 claims description 9
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 9
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 9
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 9
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 9
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 9
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000001246 bromo group Chemical group Br* 0.000 claims description 9
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 9
- 108091007196 stromelysin Proteins 0.000 claims description 9
- 108010026132 Gelatinases Proteins 0.000 claims description 8
- 102000013382 Gelatinases Human genes 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 8
- QRIWDFDMDKAYLN-UHFFFAOYSA-N n-hydroxy-3-(4-methylphenyl)sulfonyl-2-[(4-methylphenyl)sulfonylmethyl]propanamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)CC(C(=O)NO)CS(=O)(=O)C1=CC=C(C)C=C1 QRIWDFDMDKAYLN-UHFFFAOYSA-N 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- IKRTUNFYRQZJTM-UHFFFAOYSA-N 3-(4-chlorophenyl)sulfonyl-2-[(4-chlorophenyl)sulfonylmethyl]-n-hydroxypropanamide Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)CC(C(=O)NO)CS(=O)(=O)C1=CC=C(Cl)C=C1 IKRTUNFYRQZJTM-UHFFFAOYSA-N 0.000 claims description 7
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 7
- GZCALQWRAMMVSG-UHFFFAOYSA-N n-hydroxy-3-(4-methoxyphenyl)sulfonyl-2-[(4-methoxyphenyl)sulfonylmethyl]propanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)CC(C(=O)NO)CS(=O)(=O)C1=CC=C(OC)C=C1 GZCALQWRAMMVSG-UHFFFAOYSA-N 0.000 claims description 7
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- IPLYHDFUXODDGE-UHFFFAOYSA-N 3-(benzenesulfonyl)-2-(benzenesulfonylmethyl)-n-hydroxypropanamide Chemical compound C=1C=CC=CC=1S(=O)(=O)CC(C(=O)NO)CS(=O)(=O)C1=CC=CC=C1 IPLYHDFUXODDGE-UHFFFAOYSA-N 0.000 claims description 6
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 6
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 6
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- RSDVBLKBRAZECX-UHFFFAOYSA-N n-hydroxy-5-(4-methoxyphenyl)sulfonyl-2-[(4-methoxyphenyl)sulfonylmethyl]pentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)CCCC(C(=O)NO)CS(=O)(=O)C1=CC=C(OC)C=C1 RSDVBLKBRAZECX-UHFFFAOYSA-N 0.000 claims description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 5
- 102000029816 Collagenase Human genes 0.000 claims description 5
- 108060005980 Collagenase Proteins 0.000 claims description 5
- 206010027476 Metastases Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 208000007107 Stomach Ulcer Diseases 0.000 claims description 5
- 201000007717 corneal ulcer Diseases 0.000 claims description 5
- 208000007565 gingivitis Diseases 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 230000009401 metastasis Effects 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 201000001245 periodontitis Diseases 0.000 claims description 5
- 230000002062 proliferating effect Effects 0.000 claims description 5
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 206010053555 Arthritis bacterial Diseases 0.000 claims description 4
- 208000004575 Infectious Arthritis Diseases 0.000 claims description 4
- 229960002424 collagenase Drugs 0.000 claims description 4
- 201000005917 gastric ulcer Diseases 0.000 claims description 4
- SNNKEXJKGVOHRP-UHFFFAOYSA-N n-hydroxy-3-octylsulfonyl-2-(octylsulfonylmethyl)propanamide Chemical compound CCCCCCCCS(=O)(=O)CC(C(=O)NO)CS(=O)(=O)CCCCCCCC SNNKEXJKGVOHRP-UHFFFAOYSA-N 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 201000001223 septic arthritis Diseases 0.000 claims description 4
- ZNYIPTYJBRGSSL-UHFFFAOYSA-N 1,5,5-trimethylimidazolidine-2,4-dione Chemical compound CN1C(=O)NC(=O)C1(C)C ZNYIPTYJBRGSSL-UHFFFAOYSA-N 0.000 claims description 3
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 3
- PVWKZXONCXNGRR-UHFFFAOYSA-N 3-(benzenesulfonyl)-n-hydroxy-2-methylpropanamide Chemical compound ONC(=O)C(C)CS(=O)(=O)C1=CC=CC=C1 PVWKZXONCXNGRR-UHFFFAOYSA-N 0.000 claims description 3
- 125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 claims description 3
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 3
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000006189 4-phenyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 208000025865 Ulcer Diseases 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000006301 indolyl methyl group Chemical group 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 3
- 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 3
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims description 3
- 231100000397 ulcer Toxicity 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- XUJVKYNDORUCOH-UHFFFAOYSA-N 1-butyl-5,5-dimethylimidazolidine-2,4-dione Chemical compound CCCCN1C(=O)NC(=O)C1(C)C XUJVKYNDORUCOH-UHFFFAOYSA-N 0.000 claims description 2
- WTRNTDJLWVYXRB-UHFFFAOYSA-N 2-(benzenesulfonylmethyl)-n-hydroxy-3-phenylpropanamide Chemical compound C=1C=CC=CC=1S(=O)(=O)CC(C(=O)NO)CC1=CC=CC=C1 WTRNTDJLWVYXRB-UHFFFAOYSA-N 0.000 claims description 2
- BSKDSCGZWSBLGT-UHFFFAOYSA-N 2-benzyl-n-hydroxy-3-(4-methoxyphenyl)sulfonylpropanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)CC(C(=O)NO)CC1=CC=CC=C1 BSKDSCGZWSBLGT-UHFFFAOYSA-N 0.000 claims description 2
- 125000005999 2-bromoethyl group Chemical group 0.000 claims description 2
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 2
- 125000005975 2-phenylethyloxy group Chemical group 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- PWUPRWKCMAXCKI-UHFFFAOYSA-N 3-butylsulfonyl-2-(butylsulfonylmethyl)-n-hydroxypropanamide Chemical compound CCCCS(=O)(=O)CC(C(=O)NO)CS(=O)(=O)CCCC PWUPRWKCMAXCKI-UHFFFAOYSA-N 0.000 claims description 2
- 230000037396 body weight Effects 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 98
- 239000000203 mixture Substances 0.000 description 65
- 238000002360 preparation method Methods 0.000 description 64
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 55
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- 239000007787 solid Substances 0.000 description 48
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 235000019439 ethyl acetate Nutrition 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 235000019441 ethanol Nutrition 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 17
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- 239000012267 brine Substances 0.000 description 14
- 239000012141 concentrate Substances 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000012230 colorless oil Substances 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 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 description 9
- 239000000047 product Substances 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 239000012153 distilled water Substances 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
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- CHLCPTJLUJHDBO-UHFFFAOYSA-M sodium;benzenesulfinate Chemical compound [Na+].[O-]S(=O)C1=CC=CC=C1 CHLCPTJLUJHDBO-UHFFFAOYSA-M 0.000 description 1
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003443 succinic acid derivatives Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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]
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/72—Two oxygen atoms, e.g. hydantoin
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Dermatology (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)
- Lubricants (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2684896P | 1996-09-27 | 1996-09-27 | |
| US60/026,848 | 1996-09-27 | ||
| PCT/US1997/016348 WO1998013340A1 (en) | 1996-09-27 | 1997-09-19 | β-SULFONYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASES INHIBITORS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001516338A true JP2001516338A (ja) | 2001-09-25 |
| JP2001516338A5 JP2001516338A5 (https=) | 2005-05-12 |
Family
ID=21834136
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51570298A Withdrawn JP2001516338A (ja) | 1996-09-27 | 1997-09-19 | マトリックスメタロプロテイナーゼ・インヒビターとしてのβ―スルホニルヒドロキサム酸 |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US6235928B1 (https=) |
| EP (1) | EP0929519B1 (https=) |
| JP (1) | JP2001516338A (https=) |
| KR (1) | KR20000048639A (https=) |
| CN (1) | CN1158254C (https=) |
| AT (1) | ATE289590T1 (https=) |
| AU (1) | AU726799B2 (https=) |
| BR (1) | BR9712134A (https=) |
| CA (1) | CA2266368A1 (https=) |
| CZ (1) | CZ92399A3 (https=) |
| DE (1) | DE69732571T2 (https=) |
| EA (1) | EA001460B1 (https=) |
| ES (1) | ES2236829T3 (https=) |
| HU (1) | HUP0000145A3 (https=) |
| ID (1) | ID21897A (https=) |
| IL (1) | IL128900A0 (https=) |
| NO (1) | NO312893B1 (https=) |
| NZ (1) | NZ334729A (https=) |
| PL (1) | PL332509A1 (https=) |
| UA (1) | UA48262C2 (https=) |
| WO (1) | WO1998013340A1 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001524462A (ja) * | 1997-11-21 | 2001-12-04 | ファーマシア・アンド・アップジョン・カンパニー | マトリックスメタロプロテイナーゼインヒビターとしてのβ−スルホニルヒドロキサム酸のα−ヒドロキシ、−アミノ及びハロ誘導体 |
| JP2002501943A (ja) * | 1998-01-30 | 2002-01-22 | ダーウィン・ディスカバリー・リミテッド | ヒドロキサム酸およびカルボン酸誘導体 |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6566384B1 (en) * | 1996-08-07 | 2003-05-20 | Darwin Discovery Ltd. | Hydroxamic and carboxylic acid derivatives having MMP and TNF inhibitory activity |
| DE69729007T2 (de) * | 1996-08-07 | 2005-04-07 | Darwin Discovery Ltd., Slough | Hydroxamsäure- und carbonsäure-derivate mit mmp und tnf hemmender wirkung |
| WO1998013340A1 (en) * | 1996-09-27 | 1998-04-02 | Pharmacia & Upjohn Company | β-SULFONYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASES INHIBITORS |
| EP0960096B1 (en) | 1997-01-22 | 2005-04-06 | Aventis Pharmaceuticals Inc. | Substituted beta-thiocarboxylic acids |
| GB9702088D0 (en) | 1997-01-31 | 1997-03-19 | Pharmacia & Upjohn Spa | Matrix metalloproteinase inhibitors |
| US6172057B1 (en) | 1997-02-27 | 2001-01-09 | American Cyanamid Company | N-Hydroxy-2-(alkyl, aryl, or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors |
| US6362183B1 (en) | 1997-03-04 | 2002-03-26 | G. D. Searle & Company | Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds |
| US6380258B2 (en) * | 1997-03-04 | 2002-04-30 | G. D. Searle, L.L.C. | Sulfonyl divalent aryl or heteroaryl hydroxamic acid compounds |
| US6063786A (en) * | 1997-11-12 | 2000-05-16 | Darwin Discovery, Ltd. | Heterocyclic compounds having MMP and TNF inhibitory activity |
| US6187924B1 (en) * | 1997-11-12 | 2001-02-13 | Darwin Discovery, Ltd. | Hydroxamic and carboxylic acid derivatives having MMP and TNF inhibitory activity |
| EP1357109B1 (en) | 1998-06-18 | 2008-07-23 | F. Hoffmann-La Roche Ag | Process for aryl alkyl sulfide |
| GB9916562D0 (en) | 1999-07-14 | 1999-09-15 | Pharmacia & Upjohn Spa | 3-Arylsulfonyl-2-(substituted-methyl) propanoic acid derivatives as matrix metalloproteinase inhibitora |
| US6620823B2 (en) | 2000-07-11 | 2003-09-16 | Bristol-Myers Squibb Pharme Company | Lactam metalloprotease inhibitors |
| GB0017435D0 (en) * | 2000-07-14 | 2000-08-30 | Pharmacia & Upjohn Spa | 3-arylsulfonyl-2-hydroxy-2-methylpropanoic acid derivatives |
| PE20030701A1 (es) | 2001-12-20 | 2003-08-21 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
| EP2181704B1 (en) | 2002-12-30 | 2015-05-06 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
| CA2632030A1 (en) | 2005-12-15 | 2007-06-21 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
| EP2081905B1 (en) * | 2006-07-28 | 2012-09-12 | Boehringer Ingelheim International GmbH | Sulfonyl compounds which modulate the cb2 receptor |
| CA2664310A1 (en) * | 2006-09-25 | 2008-04-03 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
| JP5492092B2 (ja) * | 2007-11-07 | 2014-05-14 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｂ２受容体を調節する化合物 |
| EP2326629B1 (en) * | 2008-07-10 | 2013-10-02 | Boehringer Ingelheim International GmbH | Sulfone compounds which modulate the cb2 receptor |
| WO2010036630A2 (en) | 2008-09-25 | 2010-04-01 | Boehringer Ingelheim International Gmbh | Compounds which selectively modulate the cb2 receptor |
| US8299103B2 (en) | 2009-06-15 | 2012-10-30 | Boehringer Ingelheim International Gmbh | Compounds which selectively modulate the CB2 receptor |
| JP5756800B2 (ja) | 2009-06-16 | 2015-07-29 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｂ２受容体を調節するアゼチジン２−カルボキサミド誘導体 |
| JP2013505295A (ja) * | 2009-09-22 | 2013-02-14 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｂ２受容体を選択的に調節する化合物 |
| US9315454B2 (en) | 2010-01-15 | 2016-04-19 | Boehringer Ingelheim International Gmbh | Compounds which modulate the CB2 receptor |
| EP2542539B1 (en) | 2010-03-05 | 2014-02-26 | Boehringer Ingelheim International GmbH | Tetrazole compounds which selectively modulate the cb2 receptor |
| JP5746764B2 (ja) | 2010-07-22 | 2015-07-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｂ２受容体を調節する化合物 |
| EP2803668A1 (en) | 2013-05-17 | 2014-11-19 | Boehringer Ingelheim International Gmbh | Novel (cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB689608A (en) * | 1950-04-13 | 1953-04-01 | Basf Ag | Improvements in the production of gamma-sulphonyl carboxylic acids |
| US2659752A (en) * | 1951-08-09 | 1953-11-17 | Goodrich Co B F | Method for preparing beta-(arylsulfonyl) carboxylic acids and salts thereof |
| GB8827305D0 (en) * | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| US5525629A (en) * | 1992-04-07 | 1996-06-11 | British Bio-Technology Limited | Inhibition of cytokine production |
| DE4233100A1 (de) * | 1992-10-01 | 1994-04-07 | Hoechst Ag | Verfahren zur stereoselektiven Synthese von 3-substituierten 2-Sulfonylmethylpropionsäuren sowie Zwischenprodukte |
| DE4233099A1 (de) * | 1992-10-01 | 1994-04-07 | Hoechst Ag | Verfahren zur stereoselektiven Synthese von 3-substituierten 2-Thiomethylpropionsäuren |
| GB9223904D0 (en) * | 1992-11-13 | 1993-01-06 | British Bio Technology | Inhibition of cytokine production |
| EP0640594A1 (en) * | 1993-08-23 | 1995-03-01 | Fujirebio Inc. | Hydantoin derivative as metalloprotease inhibitor |
| GB9320660D0 (en) * | 1993-10-07 | 1993-11-24 | British Bio Technology | Inhibition of cytokine production |
| DE69624081T2 (de) * | 1995-12-20 | 2003-06-12 | Agouron Pharmaceuticals, Inc. | Matrix-metalloprotease Inhibitoren |
| JP4358908B2 (ja) * | 1996-01-02 | 2009-11-04 | アヴェンティス ファーマシューティカルズ インコーポレイテッド | 置換（アリール、ヘテロアリール、アリールメチル又はヘテロアリールメチル）ヒドロキサム酸化合物 |
| TW448172B (en) * | 1996-03-08 | 2001-08-01 | Pharmacia & Upjohn Co Llc | Novel hydroxamic acid derivatives useful for the treatment of diseases related to connective tissue degradation |
| WO1998013340A1 (en) | 1996-09-27 | 1998-04-02 | Pharmacia & Upjohn Company | β-SULFONYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASES INHIBITORS |
| US6362183B1 (en) | 1997-03-04 | 2002-03-26 | G. D. Searle & Company | Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds |
-
1997
- 1997-09-19 WO PCT/US1997/016348 patent/WO1998013340A1/en not_active Ceased
- 1997-09-19 KR KR1019990702581A patent/KR20000048639A/ko not_active Ceased
- 1997-09-19 DE DE69732571T patent/DE69732571T2/de not_active Expired - Fee Related
- 1997-09-19 NZ NZ334729A patent/NZ334729A/xx unknown
- 1997-09-19 AT AT97945207T patent/ATE289590T1/de not_active IP Right Cessation
- 1997-09-19 CZ CZ99923A patent/CZ92399A3/cs unknown
- 1997-09-19 BR BR9712134-7A patent/BR9712134A/pt active Search and Examination
- 1997-09-19 UA UA99042348A patent/UA48262C2/uk unknown
- 1997-09-19 ES ES97945207T patent/ES2236829T3/es not_active Expired - Lifetime
- 1997-09-19 CN CNB971979227A patent/CN1158254C/zh not_active Expired - Fee Related
- 1997-09-19 JP JP51570298A patent/JP2001516338A/ja not_active Withdrawn
- 1997-09-19 US US09/269,185 patent/US6235928B1/en not_active Expired - Fee Related
- 1997-09-19 HU HU0000145A patent/HUP0000145A3/hu unknown
- 1997-09-19 IL IL12890097A patent/IL128900A0/xx unknown
- 1997-09-19 ID IDW990118A patent/ID21897A/id unknown
- 1997-09-19 EP EP97945207A patent/EP0929519B1/en not_active Expired - Lifetime
- 1997-09-19 PL PL97332509A patent/PL332509A1/xx unknown
- 1997-09-19 US US08/934,408 patent/US5847153A/en not_active Expired - Fee Related
- 1997-09-19 EA EA199900332A patent/EA001460B1/ru not_active IP Right Cessation
- 1997-09-19 CA CA002266368A patent/CA2266368A1/en not_active Abandoned
- 1997-09-19 AU AU46459/97A patent/AU726799B2/en not_active Ceased
-
1999
- 1999-03-26 NO NO19991494A patent/NO312893B1/no unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001524462A (ja) * | 1997-11-21 | 2001-12-04 | ファーマシア・アンド・アップジョン・カンパニー | マトリックスメタロプロテイナーゼインヒビターとしてのβ−スルホニルヒドロキサム酸のα−ヒドロキシ、−アミノ及びハロ誘導体 |
| JP2002501943A (ja) * | 1998-01-30 | 2002-01-22 | ダーウィン・ディスカバリー・リミテッド | ヒドロキサム酸およびカルボン酸誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| DE69732571D1 (de) | 2005-03-31 |
| AU4645997A (en) | 1998-04-17 |
| CN1158254C (zh) | 2004-07-21 |
| NO991494D0 (no) | 1999-03-26 |
| NZ334729A (en) | 2001-01-26 |
| US5847153A (en) | 1998-12-08 |
| EA199900332A1 (ru) | 1999-12-29 |
| NO991494L (no) | 1999-05-26 |
| ATE289590T1 (de) | 2005-03-15 |
| ES2236829T3 (es) | 2005-07-16 |
| DE69732571T2 (de) | 2006-01-12 |
| HUP0000145A3 (en) | 2001-12-28 |
| EP0929519A1 (en) | 1999-07-21 |
| ID21897A (id) | 1999-08-05 |
| CZ92399A3 (cs) | 1999-07-14 |
| HUP0000145A2 (en) | 2000-07-28 |
| BR9712134A (pt) | 1999-08-31 |
| AU726799B2 (en) | 2000-11-23 |
| EP0929519B1 (en) | 2005-02-23 |
| US6235928B1 (en) | 2001-05-22 |
| PL332509A1 (en) | 1999-09-13 |
| NO312893B1 (no) | 2002-07-15 |
| EA001460B1 (ru) | 2001-04-23 |
| WO1998013340A1 (en) | 1998-04-02 |
| IL128900A0 (en) | 2000-01-31 |
| CN1230177A (zh) | 1999-09-29 |
| HK1022468A1 (en) | 2000-08-11 |
| CA2266368A1 (en) | 1998-04-02 |
| KR20000048639A (ko) | 2000-07-25 |
| UA48262C2 (uk) | 2002-08-15 |
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