HRP970410A2 - Butyric acid matrix metalloproteinase inhibitors - Google Patents

Butyric acid matrix metalloproteinase inhibitors

Info

Publication number: HRP970410A2
Authority: HR; Croatia
Prior art keywords: oxo; butyric acid; dibenzofuran; compound; amino
Prior art date: 1996-08-16

Application number

HR60/024,025A

Other languages

English (en)

Croatian (hr)

Inventor

Joseph Armant Picard

Original Assignee

Joseph Armant Picard

Priority date (The priority date 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 date listed.)

1996-08-16

Filing date

1997-07-23

Publication date

1998-08-31

1997-07-23 Application filed by Joseph Armant Picard filed Critical Joseph Armant Picard

1998-08-31 Publication of HRP970410A2 publication Critical patent/HRP970410A2/hr

Links

239000003771 matrix metalloproteinase inhibitor Substances 0.000 title description 2
229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 title 2
239000001257 hydrogen Substances 0.000 claims abstract description 29
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
229910052717 sulfur Inorganic materials 0.000 claims abstract description 20
102000002274 Matrix Metalloproteinases Human genes 0.000 claims abstract description 19
108010000684 Matrix Metalloproteinases Proteins 0.000 claims abstract description 19
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 11
125000000217 alkyl group Chemical group 0.000 claims abstract description 10
230000002401 inhibitory effect Effects 0.000 claims abstract description 8
125000003118 aryl group Chemical group 0.000 claims abstract description 7
150000001875 compounds Chemical class 0.000 claims description 110
-1 4-dibenzofuran-2-yl-2-(3,4-dichloro-benzoylamino)-4-oxo-butyric acid Chemical compound 0.000 claims description 86
238000000034 method Methods 0.000 claims description 27
125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 12
125000001072 heteroaryl group Chemical group 0.000 claims description 12
150000002431 hydrogen Chemical class 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 8
NUZCSVKFVKXZEM-LBPRGKRZSA-N (2s)-4-dibenzofuran-2-yl-4-oxo-2-[(2,2,2-trifluoroacetyl)amino]butanoic acid Chemical group C1=CC=C2C3=CC(C(=O)C[C@@H](C(=O)O)NC(=O)C(F)(F)F)=CC=C3OC2=C1 NUZCSVKFVKXZEM-LBPRGKRZSA-N 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
101100134925 Gallus gallus COR6 gene Proteins 0.000 claims description 6
206010003246 arthritis Diseases 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
201000006417 multiple sclerosis Diseases 0.000 claims description 5
DCXSZYLYDZGFMN-LBPRGKRZSA-N (2s)-2-amino-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C1=CC=C2C3=CC(C(=O)C[C@H](N)C(O)=O)=CC=C3OC2=C1 DCXSZYLYDZGFMN-LBPRGKRZSA-N 0.000 claims description 4
208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 4
206010019280 Heart failures Diseases 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
208000037803 restenosis Diseases 0.000 claims description 4
239000012453 solvate Substances 0.000 claims description 4
NUZCSVKFVKXZEM-GFCCVEGCSA-N (2r)-4-dibenzofuran-2-yl-4-oxo-2-[(2,2,2-trifluoroacetyl)amino]butanoic acid Chemical group C1=CC=C2C3=CC(C(=O)C[C@H](C(=O)O)NC(=O)C(F)(F)F)=CC=C3OC2=C1 NUZCSVKFVKXZEM-GFCCVEGCSA-N 0.000 claims description 3
125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 3
208000007474 aortic aneurysm Diseases 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
208000028169 periodontal disease Diseases 0.000 claims description 3
230000029663 wound healing Effects 0.000 claims description 3
MCBFGLOCAYSWIG-IBGZPJMESA-N (2s)-4-dibenzofuran-2-yl-2-(octanoylamino)-4-oxobutanoic acid Chemical compound C1=CC=C2C3=CC(C(=O)C[C@H](NC(=O)CCCCCCC)C(O)=O)=CC=C3OC2=C1 MCBFGLOCAYSWIG-IBGZPJMESA-N 0.000 claims description 2
LWMATGKIVQPBTO-FQEVSTJZSA-N (2s)-4-dibenzofuran-2-yl-4-oxo-2-(3-phenylpropanoylamino)butanoic acid Chemical compound N([C@@H](CC(=O)C=1C=C2C3=CC=CC=C3OC2=CC=1)C(=O)O)C(=O)CCC1=CC=CC=C1 LWMATGKIVQPBTO-FQEVSTJZSA-N 0.000 claims description 2
BBIUWUFUMFZBLS-DEOSSOPVSA-N (2s)-4-dibenzofuran-2-yl-4-oxo-2-(7-phenylheptanoylamino)butanoic acid Chemical compound N([C@@H](CC(=O)C=1C=C2C3=CC=CC=C3OC2=CC=1)C(=O)O)C(=O)CCCCCCC1=CC=CC=C1 BBIUWUFUMFZBLS-DEOSSOPVSA-N 0.000 claims description 2
NMCAXOLGEVSANY-IBGZPJMESA-N (2s)-4-dibenzofuran-2-yl-4-oxo-2-[(2-phenylacetyl)amino]butanoic acid Chemical compound N([C@@H](CC(=O)C=1C=C2C3=CC=CC=C3OC2=CC=1)C(=O)O)C(=O)CC1=CC=CC=C1 NMCAXOLGEVSANY-IBGZPJMESA-N 0.000 claims description 2
DTTSJWNGBWEGJL-DEOSSOPVSA-N (2s)-4-dibenzofuran-2-yl-4-oxo-2-[(4-phenylbenzoyl)amino]butanoic acid Chemical compound N([C@@H](CC(=O)C=1C=C2C3=CC=CC=C3OC2=CC=1)C(=O)O)C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 DTTSJWNGBWEGJL-DEOSSOPVSA-N 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
ZHMTXQMPTXZPIY-QHCPKHFHSA-N (2s)-4-dibenzofuran-2-yl-2-(dodecanoylamino)-4-oxobutanoic acid Chemical compound C1=CC=C2C3=CC(C(=O)C[C@H](NC(=O)CCCCCCCCCCC)C(O)=O)=CC=C3OC2=C1 ZHMTXQMPTXZPIY-QHCPKHFHSA-N 0.000 claims 1
HMMCXHVGTKAARV-UHFFFAOYSA-N 2-(1,3-benzodioxole-5-carbonylamino)-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C1=C2OCOC2=CC(C(=O)NC(CC(=O)C=2C=C3C4=CC=CC=C4OC3=CC=2)C(=O)O)=C1 HMMCXHVGTKAARV-UHFFFAOYSA-N 0.000 claims 1
HASXPTMFXLKZKB-UHFFFAOYSA-N 2-(adamantane-1-carbonylamino)-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C1C(C2)CC(C3)CC2CC13C(=O)NC(C(=O)O)CC(=O)C1=CC=C(OC=2C3=CC=CC=2)C3=C1 HASXPTMFXLKZKB-UHFFFAOYSA-N 0.000 claims 1
UXDFOPWGKCLXHB-UHFFFAOYSA-N 2-(cyclohexanecarbonylamino)-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1CCCCC1 UXDFOPWGKCLXHB-UHFFFAOYSA-N 0.000 claims 1
GWMJIXUSSXSMRG-UHFFFAOYSA-N 2-(cyclopentanecarbonylamino)-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1CCCC1 GWMJIXUSSXSMRG-UHFFFAOYSA-N 0.000 claims 1
QMGUDKMWDWCBCQ-UHFFFAOYSA-N 2-(cyclopropanecarbonylamino)-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1CC1 QMGUDKMWDWCBCQ-UHFFFAOYSA-N 0.000 claims 1
IAUWMCHCESSGHL-UHFFFAOYSA-N 2-[(4-bromobenzoyl)amino]-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1=CC=C(Br)C=C1 IAUWMCHCESSGHL-UHFFFAOYSA-N 0.000 claims 1
VHHBVCKJVFFDSS-UHFFFAOYSA-N 2-[(4-butylbenzoyl)amino]-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C1=CC(CCCC)=CC=C1C(=O)NC(C(O)=O)CC(=O)C1=CC=C(OC=2C3=CC=CC=2)C3=C1 VHHBVCKJVFFDSS-UHFFFAOYSA-N 0.000 claims 1
HUJUWEKZEQREME-UHFFFAOYSA-N 2-[(4-chlorobenzoyl)amino]-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1=CC=C(Cl)C=C1 HUJUWEKZEQREME-UHFFFAOYSA-N 0.000 claims 1
CREGTWRJJNAHQG-UHFFFAOYSA-N 2-[(4-cyanobenzoyl)amino]-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1=CC=C(C#N)C=C1 CREGTWRJJNAHQG-UHFFFAOYSA-N 0.000 claims 1
UTVGLHADICPSSD-UHFFFAOYSA-N 2-[4-(4-bromophenyl)butanoylamino]-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)CCCC1=CC=C(Br)C=C1 UTVGLHADICPSSD-UHFFFAOYSA-N 0.000 claims 1
MXXFRVNFZOBQEA-UHFFFAOYSA-N 2-[[2-(4-chlorophenoxy)acetyl]amino]-4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)COC1=CC=C(Cl)C=C1 MXXFRVNFZOBQEA-UHFFFAOYSA-N 0.000 claims 1
MAUSDPNSKAJRAU-UHFFFAOYSA-N 4-dibenzofuran-2-yl-2-(2,2-dimethylpentanoylamino)-4-oxobutanoic acid Chemical compound C1=CC=C2C3=CC(C(=O)CC(NC(=O)C(C)(C)CCC)C(O)=O)=CC=C3OC2=C1 MAUSDPNSKAJRAU-UHFFFAOYSA-N 0.000 claims 1
JISXRAXWLHYCBR-UHFFFAOYSA-N 4-dibenzofuran-2-yl-2-(furan-2-carbonylamino)-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1=CC=CO1 JISXRAXWLHYCBR-UHFFFAOYSA-N 0.000 claims 1
WFNXXSWVNGQMDP-UHFFFAOYSA-N 4-dibenzofuran-2-yl-2-(heptanoylamino)-4-oxobutanoic acid Chemical compound C1=CC=C2C3=CC(C(=O)CC(NC(=O)CCCCCC)C(O)=O)=CC=C3OC2=C1 WFNXXSWVNGQMDP-UHFFFAOYSA-N 0.000 claims 1
AKGXVDYGGPDGJB-UHFFFAOYSA-N 4-dibenzofuran-2-yl-2-(naphthalene-2-carbonylamino)-4-oxobutanoic acid Chemical compound C1=CC=CC2=CC(C(=O)NC(CC(=O)C=3C=C4C5=CC=CC=C5OC4=CC=3)C(=O)O)=CC=C21 AKGXVDYGGPDGJB-UHFFFAOYSA-N 0.000 claims 1
ISLYILJAMSURDT-UHFFFAOYSA-N 4-dibenzofuran-2-yl-2-[(2,2-diphenylacetyl)amino]-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 ISLYILJAMSURDT-UHFFFAOYSA-N 0.000 claims 1
GKCMMGCOHRRRFU-UHFFFAOYSA-N 4-dibenzofuran-2-yl-2-[(3,4-dimethoxybenzoyl)amino]-4-oxobutanoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NC(C(O)=O)CC(=O)C1=CC=C(OC=2C3=CC=CC=2)C3=C1 GKCMMGCOHRRRFU-UHFFFAOYSA-N 0.000 claims 1
XKNLHOFJVPPFQT-UHFFFAOYSA-N 4-dibenzofuran-2-yl-2-[(4-fluorobenzoyl)amino]-4-oxobutanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1=CC=C(F)C=C1 XKNLHOFJVPPFQT-UHFFFAOYSA-N 0.000 claims 1
ZYNFIARWEIOWNN-UHFFFAOYSA-N 4-dibenzofuran-2-yl-2-[(4-methylbenzoyl)amino]-4-oxobutanoic acid Chemical compound C1=CC(C)=CC=C1C(=O)NC(C(O)=O)CC(=O)C1=CC=C(OC=2C3=CC=CC=2)C3=C1 ZYNFIARWEIOWNN-UHFFFAOYSA-N 0.000 claims 1
KBXCQKVSWISGFJ-UHFFFAOYSA-N 4-dibenzofuran-2-yl-2-[[2-(3,4-dimethoxyphenyl)acetyl]amino]-4-oxobutanoic acid Chemical compound C1=C(OC)C(OC)=CC=C1CC(=O)NC(C(O)=O)CC(=O)C1=CC=C(OC=2C3=CC=CC=2)C3=C1 KBXCQKVSWISGFJ-UHFFFAOYSA-N 0.000 claims 1
ITMGYNMHQAJYDJ-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctanoylamino)butanoic acid Chemical compound C1=CC=C2C3=CC(C(=O)CC(C(=O)O)NC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)=CC=C3OC2=C1 ITMGYNMHQAJYDJ-UHFFFAOYSA-N 0.000 claims 1
BZIWHFIMRGOBIT-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-(2-phenoxypropanoylamino)butanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(O)=O)NC(=O)C(C)OC1=CC=CC=C1 BZIWHFIMRGOBIT-UHFFFAOYSA-N 0.000 claims 1
IEYMDUDPYODVMS-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-(2-phenylbutanoylamino)butanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(O)=O)NC(=O)C(CC)C1=CC=CC=C1 IEYMDUDPYODVMS-UHFFFAOYSA-N 0.000 claims 1
PJLGAMHTQUZYGU-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-(3-phenylprop-2-enoylamino)butanoic acid Chemical group C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C=CC1=CC=CC=C1 PJLGAMHTQUZYGU-UHFFFAOYSA-N 0.000 claims 1
SAXKXTMKPHBRFQ-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-(pyridine-2-carbonylamino)butanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1=CC=CC=N1 SAXKXTMKPHBRFQ-UHFFFAOYSA-N 0.000 claims 1
PMUUSSWBQQAGDP-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-(pyridine-4-carbonylamino)butanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1=CC=NC=C1 PMUUSSWBQQAGDP-UHFFFAOYSA-N 0.000 claims 1
ADOQKCFUCHLNGM-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-(quinoxaline-2-carbonylamino)butanoic acid Chemical compound C1=CC=CC2=NC(C(=O)NC(CC(=O)C=3C=C4C5=CC=CC=C5OC4=CC=3)C(=O)O)=CN=C21 ADOQKCFUCHLNGM-UHFFFAOYSA-N 0.000 claims 1
UQLILBNWYVUXJH-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-(thiophene-2-carbonylamino)butanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1=CC=CS1 UQLILBNWYVUXJH-UHFFFAOYSA-N 0.000 claims 1
JAFDGIOTAZMZJS-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-[(2,3,4,5,6-pentafluorobenzoyl)amino]butanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F JAFDGIOTAZMZJS-UHFFFAOYSA-N 0.000 claims 1
WCOPGDBARTUQMG-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-[(2-phenoxyacetyl)amino]butanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)COC1=CC=CC=C1 WCOPGDBARTUQMG-UHFFFAOYSA-N 0.000 claims 1
CDTUVUWJAKBTBC-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-[(2-phenylmethoxyacetyl)amino]butanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)COCC1=CC=CC=C1 CDTUVUWJAKBTBC-UHFFFAOYSA-N 0.000 claims 1
FBBNDBMGOOWVNN-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxo-2-[(2-thiophen-2-ylacetyl)amino]butanoic acid Chemical compound C=1C=C2OC3=CC=CC=C3C2=CC=1C(=O)CC(C(=O)O)NC(=O)CC1=CC=CS1 FBBNDBMGOOWVNN-UHFFFAOYSA-N 0.000 claims 1
125000003860 C1-C20 alkoxy group Chemical group 0.000 claims 1
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
201000010099 disease Diseases 0.000 abstract description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
125000000547 substituted alkyl group Chemical group 0.000 abstract description 6
210000002808 connective tissue Anatomy 0.000 abstract description 5
125000003545 alkoxy group Chemical group 0.000 abstract description 2
230000015556 catabolic process Effects 0.000 abstract description 2
241001465754 Metazoa Species 0.000 abstract 1
125000003710 aryl alkyl group Chemical group 0.000 abstract 1
125000001475 halogen functional group Chemical group 0.000 abstract 1
125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
239000000243 solution Substances 0.000 description 32
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 19
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
238000002844 melting Methods 0.000 description 15
239000007787 solid Substances 0.000 description 15
239000000203 mixture Substances 0.000 description 14
238000002360 preparation method Methods 0.000 description 14
230000008018 melting Effects 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
150000003141 primary amines Chemical class 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
239000000047 product Substances 0.000 description 8
239000000758 substrate Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
239000003826 tablet Substances 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
230000006378 damage Effects 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000002775 capsule Substances 0.000 description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000000843 powder Substances 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
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239000007900 aqueous suspension Substances 0.000 description 1
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125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
238000003556 assay Methods 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
239000002585 base Substances 0.000 description 1
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125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
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238000009835 boiling Methods 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
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239000000872 buffer Substances 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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239000001110 calcium chloride Substances 0.000 description 1
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239000001506 calcium phosphate Substances 0.000 description 1
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235000011010 calcium phosphates Nutrition 0.000 description 1
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239000000969 carrier Substances 0.000 description 1
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238000004140 cleaning Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
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239000007822 coupling agent Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
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125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
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125000000524 functional group Chemical group 0.000 description 1
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125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
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125000001041 indolyl group Chemical group 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
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HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
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GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
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125000001288 lysyl group Chemical group 0.000 description 1
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239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000003475 metalloproteinase inhibitor Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
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229940102396 methyl bromide Drugs 0.000 description 1
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239000011812 mixed powder Substances 0.000 description 1
239000011259 mixed solution Substances 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
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239000006201 parenteral dosage form Substances 0.000 description 1
239000003182 parenteral nutrition solution Substances 0.000 description 1
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238000005897 peptide coupling reaction Methods 0.000 description 1
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MCJXDWRORUZWER-UHFFFAOYSA-N phenylmethanesulfonyl bromide Chemical compound BrS(=O)(=O)CC1=CC=CC=C1 MCJXDWRORUZWER-UHFFFAOYSA-N 0.000 description 1
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229920001223 polyethylene glycol Polymers 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
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235000011181 potassium carbonates Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
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238000010791 quenching Methods 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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239000000376 reactant Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
229940087562 sodium acetate trihydrate Drugs 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000000600 sorbitol Substances 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
210000002784 stomach Anatomy 0.000 description 1
108091007196 stromelysin Proteins 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000005415 substituted alkoxy group Chemical group 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000007885 tablet disintegrant Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000003556 thioamides Chemical class 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
230000036269 ulceration Effects 0.000 description 1
125000000297 undecanoyl group Chemical group O=C([*])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
230000002861 ventricular Effects 0.000 description 1
239000011345 viscous material Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
- 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
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Rheumatology (AREA)
Physical Education & Sports Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Psychiatry (AREA)
Immunology (AREA)
Orthopedic Medicine & Surgery (AREA)
Cardiology (AREA)
Hospice & Palliative Care (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)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Plural Heterocyclic Compounds (AREA)
Furan Compounds (AREA)
Enzymes And Modification Thereof (AREA)

HR60/024,025A 1996-08-16 1997-07-23 Butyric acid matrix metalloproteinase inhibitors HRP970410A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US2402596P	1996-08-16	1996-08-16

Publications (1)

Publication Number	Publication Date
HRP970410A2 true HRP970410A2 (en)	1998-08-31

Family

ID=21818459

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR60/024,025A HRP970410A2 (en)	1996-08-16	1997-07-23	Butyric acid matrix metalloproteinase inhibitors

Country Status (11)

Country	Link
US (1)	US6020366A (de)
EP (1)	EP0923569B1 (de)
JP (1)	JP2000516607A (de)
AT (1)	ATE282602T1 (de)
AU (1)	AU3729397A (de)
CO (1)	CO4900041A1 (de)
DE (1)	DE69731642T2 (de)
ES (1)	ES2231879T3 (de)
HR (1)	HRP970410A2 (de)
WO (1)	WO1998006711A1 (de)
ZA (1)	ZA977328B (de)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE282602T1 (de) *	1996-08-16	2004-12-15	Warner Lambert Co	Buttersäure matrix-metalloproteinase-inhibitoren
AU4229499A (en)	1998-07-30	2000-02-21	Warner-Lambert Company	Tricyclic heteroaromatics and their derivatives as inhibitors of matrix metalloproteinases
NZ509439A (en)	1998-07-30	2002-10-25	Warner Lambert Co	Tricyclic sulfonamides and their derivatives as inhibitors of matrix metalloproteinases
US7325009B1 (en)	2000-06-30	2008-01-29	Brightpoint, Inc.	Customer-controlled inventory access
CN1732023A (zh) *	2002-12-27	2006-02-08	血管技术国际股份公司	组合物和使用collajolie的方法
US20040225077A1 (en)	2002-12-30	2004-11-11	Angiotech International Ag	Drug delivery from rapid gelling polymer composition
CN109996541A (zh)	2016-09-07	2019-07-09	普利安特治疗公司	N-酰基氨基酸化合物及其使用方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IE54551B1 (en) *	1982-01-22	1989-11-22	Ici Plc	Amide derivatives
US5114953A (en) *	1990-11-21	1992-05-19	University Of Florida	Treatment for tissue ulceration
US5506242A (en) *	1993-01-06	1996-04-09	Ciba-Geigy Corporation	Arylsufonamido-substituted hydroxamic acids
IT1265101B1 (it) *	1993-07-23	1996-10-30	Erba Carlo Spa	Derivati dell'acido 2-ammino-4-fenil-4-osso butirrico
NZ288299A (en) *	1994-06-22	1998-06-26	British Biotech Pharm	Substituted (hetero)aryl-sulphonylaminomethyl-hydroxamic acid and medicaments
US5665764A (en) *	1995-06-02	1997-09-09	Warner-Lambert Company	Tricyclic inhibitors of matrix metalloproteinases
ATE282602T1 (de) *	1996-08-16	2004-12-15	Warner Lambert Co	Buttersäure matrix-metalloproteinase-inhibitoren

1997
- 1997-07-16 AT AT97934175T patent/ATE282602T1/de not_active IP Right Cessation
- 1997-07-16 US US09/171,833 patent/US6020366A/en not_active Expired - Fee Related
- 1997-07-16 ES ES97934175T patent/ES2231879T3/es not_active Expired - Lifetime
- 1997-07-16 DE DE69731642T patent/DE69731642T2/de not_active Expired - Fee Related
- 1997-07-16 AU AU37293/97A patent/AU3729397A/en not_active Abandoned
- 1997-07-16 WO PCT/US1997/012389 patent/WO1998006711A1/en not_active Ceased
- 1997-07-16 EP EP97934175A patent/EP0923569B1/de not_active Expired - Lifetime
- 1997-07-16 JP JP10509712A patent/JP2000516607A/ja not_active Abandoned
- 1997-07-23 HR HR60/024,025A patent/HRP970410A2/hr not_active Application Discontinuation
- 1997-08-14 ZA ZA9707328A patent/ZA977328B/xx unknown
- 1997-08-15 CO CO97047221A patent/CO4900041A1/es unknown

Also Published As

Publication number	Publication date
EP0923569B1 (de)	2004-11-17
JP2000516607A (ja)	2000-12-12
ZA977328B (en)	1998-02-19
AU3729397A (en)	1998-03-06
ATE282602T1 (de)	2004-12-15
EP0923569A1 (de)	1999-06-23
ES2231879T3 (es)	2005-05-16
DE69731642D1 (de)	2004-12-23
CO4900041A1 (es)	2000-03-27
WO1998006711A1 (en)	1998-02-19
US6020366A (en)	2000-02-01
DE69731642T2 (de)	2005-12-01

Legal Events

Date	Code	Title
1998-08-31	A1OB	Publication of a patent application
1999-02-26	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2005-09-19	ODBC	Application rejected

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EP0934267B1 (de)	2002-01-30	Alpha-amino sulfonyl hydroxamsäure als matrix metalloproteinase inhibitoren
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