HRP970410A2 - Butyric acid matrix metalloproteinase inhibitors - Google Patents
Butyric acid matrix metalloproteinase inhibitorsInfo
- Publication number
- HRP970410A2 HRP970410A2 HR60/024,025A HRP970410A HRP970410A2 HR P970410 A2 HRP970410 A2 HR P970410A2 HR P970410 A HRP970410 A HR P970410A HR P970410 A2 HRP970410 A2 HR P970410A2
- Authority
- HR
- Croatia
- Prior art keywords
- oxo
- butyric acid
- dibenzofuran
- compound
- amino
- Prior art date
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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- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
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- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
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- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
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- 125000001309 chloro group Chemical group Cl* 0.000 description 1
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- 239000011630 iodine Substances 0.000 description 1
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- 150000002500 ions Chemical class 0.000 description 1
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- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
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- 239000011259 mixed solution Substances 0.000 description 1
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- 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
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
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- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 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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- 239000002244 precipitate Substances 0.000 description 1
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- 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
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- 235000019698 starch Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
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- 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
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- 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
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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)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Hospice & Palliative Care (AREA)
- Physical Education & Sports Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Cardiology (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)
- Enzymes And Modification Thereof (AREA)
- Lubricants (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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 (ja) |
| EP (1) | EP0923569B1 (ja) |
| JP (1) | JP2000516607A (ja) |
| AT (1) | ATE282602T1 (ja) |
| AU (1) | AU3729397A (ja) |
| CO (1) | CO4900041A1 (ja) |
| DE (1) | DE69731642T2 (ja) |
| ES (1) | ES2231879T3 (ja) |
| HR (1) | HRP970410A2 (ja) |
| WO (1) | WO1998006711A1 (ja) |
| ZA (1) | ZA977328B (ja) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000516607A (ja) * | 1996-08-16 | 2000-12-12 | ワーナー―ランバート・コンパニー | 酪酸マトリックスメタロプロテイナーゼ阻害剤 |
| HUP0102714A3 (en) | 1998-07-30 | 2003-01-28 | Warner Lambert Co | Tricyclic sulfonamid derivatives as inhibitors of matrix metalloproteinases and medicaments containing the same |
| AU4229499A (en) | 1998-07-30 | 2000-02-21 | Warner-Lambert Company | Tricyclic heteroaromatics and their derivatives as inhibitors of matrix metalloproteinases |
| US7325009B1 (en) | 2000-06-30 | 2008-01-29 | Brightpoint, Inc. | Customer-controlled inventory access |
| JP2006516252A (ja) * | 2002-12-27 | 2006-06-29 | アンジオテック インターナショナル アクツィエン ゲゼルシャフト | コラーゲンおよびｍｍｐｉを用いる組成物および方法 |
| AU2003300076C1 (en) | 2002-12-30 | 2010-03-04 | 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)
| 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 |
| CN1151157A (zh) * | 1994-06-22 | 1997-06-04 | 英国生物技术药物有限公司 | 金属蛋白酶抑制剂 |
| US5665764A (en) * | 1995-06-02 | 1997-09-09 | Warner-Lambert Company | Tricyclic inhibitors of matrix metalloproteinases |
| JP2000516607A (ja) * | 1996-08-16 | 2000-12-12 | ワーナー―ランバート・コンパニー | 酪酸マトリックスメタロプロテイナーゼ阻害剤 |
-
1997
- 1997-07-16 JP JP10509712A patent/JP2000516607A/ja not_active Abandoned
- 1997-07-16 EP EP97934175A patent/EP0923569B1/en not_active Expired - Lifetime
- 1997-07-16 WO PCT/US1997/012389 patent/WO1998006711A1/en active IP Right Grant
- 1997-07-16 AU AU37293/97A patent/AU3729397A/en not_active Abandoned
- 1997-07-16 AT AT97934175T patent/ATE282602T1/de not_active IP Right Cessation
- 1997-07-16 DE DE69731642T patent/DE69731642T2/de not_active Expired - Fee Related
- 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
- 1997-07-23 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 |
|---|---|
| ES2231879T3 (es) | 2005-05-16 |
| EP0923569B1 (en) | 2004-11-17 |
| CO4900041A1 (es) | 2000-03-27 |
| DE69731642D1 (de) | 2004-12-23 |
| ZA977328B (en) | 1998-02-19 |
| WO1998006711A1 (en) | 1998-02-19 |
| DE69731642T2 (de) | 2005-12-01 |
| US6020366A (en) | 2000-02-01 |
| EP0923569A1 (en) | 1999-06-23 |
| AU3729397A (en) | 1998-03-06 |
| JP2000516607A (ja) | 2000-12-12 |
| ATE282602T1 (de) | 2004-12-15 |
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