HRP970453A2 - Arylsulfonylamino hydroxamic acid derivatives - Google Patents
Arylsulfonylamino hydroxamic acid derivativesInfo
- Publication number
- HRP970453A2 HRP970453A2 HR60/024,675A HRP970453A HRP970453A2 HR P970453 A2 HRP970453 A2 HR P970453A2 HR P970453 A HRP970453 A HR P970453A HR P970453 A2 HRP970453 A2 HR P970453A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- aryl
- amino
- heteroaryl
- benzenesulfonyl
- Prior art date
Links
- -1 Arylsulfonylamino hydroxamic Chemical compound 0.000 title claims description 78
- 239000002253 acid Substances 0.000 title description 15
- 150000001875 compounds Chemical class 0.000 claims description 80
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 60
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 26
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 26
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 230000005764 inhibitory process Effects 0.000 claims description 20
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000006719 (C6-C10) aryl (C1-C6) alkyl group Chemical group 0.000 claims description 14
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 14
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 12
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 10
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 125000002393 azetidinyl group Chemical group 0.000 claims description 8
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 7
- 206010040047 Sepsis Diseases 0.000 claims description 6
- 206010040070 Septic Shock Diseases 0.000 claims description 6
- 208000025865 Ulcer Diseases 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 6
- 208000028169 periodontal disease Diseases 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 230000036303 septic shock Effects 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 231100000397 ulcer Toxicity 0.000 claims description 6
- 208000030507 AIDS Diseases 0.000 claims description 5
- 206010039705 Scleritis Diseases 0.000 claims description 5
- 229940035676 analgesics Drugs 0.000 claims description 5
- 239000000730 antalgic agent Substances 0.000 claims description 5
- 231100000433 cytotoxic Toxicity 0.000 claims description 5
- 230000001472 cytotoxic effect Effects 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 206010014989 Epidermolysis bullosa Diseases 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 claims description 4
- YYGXSXMKOALHSY-UHFFFAOYSA-N ethyl 1-[3-[[1-cyclohexyl-2-(hydroxyamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]propanoyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)CCN(S(=O)(=O)C=1C=CC(OC)=CC=1)C(C(=O)NO)C1CCCCC1 YYGXSXMKOALHSY-UHFFFAOYSA-N 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 208000002780 macular degeneration Diseases 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000005936 piperidyl group Chemical group 0.000 claims description 4
- 229940080818 propionamide Drugs 0.000 claims description 4
- RDPDVZHMIQZOOF-UHFFFAOYSA-N 1-[3-[[1-cyclohexyl-2-(hydroxyamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]propanoyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(C1CCCCC1)C(=O)NO)CCC(=O)N1CCC(C(O)=O)CC1 RDPDVZHMIQZOOF-UHFFFAOYSA-N 0.000 claims description 3
- VJHJDEUUCPMADI-UHFFFAOYSA-N 2,3-dihydro-1h-inden-5-yl 3-[[1-cyclohexyl-2-(hydroxyamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]propanoate Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(C1CCCCC1)C(=O)NO)CCC(=O)OC1=CC=C(CCC2)C2=C1 VJHJDEUUCPMADI-UHFFFAOYSA-N 0.000 claims description 3
- 150000008575 L-amino acids Chemical class 0.000 claims description 3
- IIRGRPFADBGAGK-UHFFFAOYSA-N [1-[3-[[1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-methoxyphenyl)sulfonylamino]propanoyl]piperidin-4-yl] acetate Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(C(C)C)C(=O)NO)CCC(=O)N1CCC(OC(C)=O)CC1 IIRGRPFADBGAGK-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- FDDVYQSFBLLBLU-UHFFFAOYSA-N n-hydroxy-2-[[3-(4-hydroxypiperidin-1-yl)-3-oxopropyl]-(4-methoxyphenyl)sulfonylamino]-3-methylbutanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(C(C)C)C(=O)NO)CCC(=O)N1CCC(O)CC1 FDDVYQSFBLLBLU-UHFFFAOYSA-N 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 125000006720 (C1-C6) alkyl (C6-C10) aryl group Chemical group 0.000 claims description 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 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 description 2
- ACFCRTQFMQXAHZ-UHFFFAOYSA-N 2-[4-[3-[[1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-methoxyphenyl)sulfonylamino]propanoyl]piperazin-1-yl]ethyl 2,2-dimethylpropanoate Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(C(C)C)C(=O)NO)CCC(=O)N1CCN(CCOC(=O)C(C)(C)C)CC1 ACFCRTQFMQXAHZ-UHFFFAOYSA-N 0.000 claims description 2
- POHLQQJCUDBBFW-UHFFFAOYSA-N 2-[4-[3-[[1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-methoxyphenyl)sulfonylamino]propanoyl]piperazin-1-yl]ethyl benzoate Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(C(C)C)C(=O)NO)CCC(=O)N1CCN(CCOC(=O)C=2C=CC=CC=2)CC1 POHLQQJCUDBBFW-UHFFFAOYSA-N 0.000 claims description 2
- RVXABMHTWPAPCO-UHFFFAOYSA-N 2-[[4-(4-butylphenoxy)phenyl]sulfonyl-[3-(4-hydroxypiperidin-1-yl)-3-oxopropyl]amino]-n-hydroxy-3-methylbutanamide Chemical compound C1=CC(CCCC)=CC=C1OC1=CC=C(S(=O)(=O)N(CCC(=O)N2CCC(O)CC2)C(C(C)C)C(=O)NO)C=C1 RVXABMHTWPAPCO-UHFFFAOYSA-N 0.000 claims description 2
- DGHRLJNUXXHBBJ-UHFFFAOYSA-N 2-cyclohexyl-2-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[3-(4-hydroxypiperidin-1-yl)-3-oxopropyl]amino]-n-hydroxyacetamide Chemical compound C1CC(O)CCN1C(=O)CCN(S(=O)(=O)C=1C=CC(OC=2C=CC(F)=CC=2)=CC=1)C(C(=O)NO)C1CCCCC1 DGHRLJNUXXHBBJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- IYBFAWXEVQJOOK-UHFFFAOYSA-N ethoxycarbonyloxymethyl 3-[(1-amino-2-hydroxy-3-methyl-1-oxobutan-2-yl)-[4-[(4-fluorophenyl)methoxy]phenyl]sulfonylamino]propanoate Chemical compound C(C)OC(=O)OCOC(CCN(C(C(C)C)(O)C(N)=O)S(=O)(=O)C1=CC=C(C=C1)OCC1=CC=C(C=C1)F)=O IYBFAWXEVQJOOK-UHFFFAOYSA-N 0.000 claims description 2
- OXEVBTQXBUGVOZ-UHFFFAOYSA-N ethoxycarbonyloxymethyl 3-[[1-(hydroxyamino)-1-oxohexan-2-yl]-(4-methoxyphenyl)sulfonylamino]propanoate Chemical compound CCOC(=O)OCOC(=O)CCN(C(CCCC)C(=O)NO)S(=O)(=O)C1=CC=C(OC)C=C1 OXEVBTQXBUGVOZ-UHFFFAOYSA-N 0.000 claims description 2
- OTXRGOWUZRTWRY-UHFFFAOYSA-N ethoxycarbonyloxymethyl 3-[[1-cyclohexyl-2-(hydroxyamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]propanoate Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)N(CCC(=O)OCOC(=O)OCC)C(C(=O)NO)C1CCCCC1 OTXRGOWUZRTWRY-UHFFFAOYSA-N 0.000 claims description 2
- KFJNJNHLFOYCEH-UHFFFAOYSA-N ethyl 4-[3-[[1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-methoxyphenyl)sulfonylamino]propanoyl]piperazine-2-carboxylate Chemical compound C1CNC(C(=O)OCC)CN1C(=O)CCN(C(C(C)C)C(=O)NO)S(=O)(=O)C1=CC=C(OC)C=C1 KFJNJNHLFOYCEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 2
- PELDTXBSNDSZOG-UHFFFAOYSA-N n-hydroxy-2-[[3-(4-hydroxypiperidin-1-yl)-3-oxopropyl]-(4-phenylmethoxyphenyl)sulfonylamino]-3-methylbutanamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1S(=O)(=O)N(C(C(C)C)C(=O)NO)CCC(=O)N1CCC(O)CC1 PELDTXBSNDSZOG-UHFFFAOYSA-N 0.000 claims description 2
- FGEAIMWSTJVRJE-UHFFFAOYSA-N n-hydroxy-2-[[3-[4-(2-hydroxy-2-methylpropyl)piperazin-1-yl]-3-oxopropyl]-(4-methoxyphenyl)sulfonylamino]-3-methylbutanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(C(C)C)C(=O)NO)CCC(=O)N1CCN(CC(C)(C)O)CC1 FGEAIMWSTJVRJE-UHFFFAOYSA-N 0.000 claims description 2
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- GRSGSWSMFLUWKY-UHFFFAOYSA-N 2-hydroxy-2-[[3-[5-(2-hydroxyethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-oxopropyl]-(4-methoxyphenyl)sulfonylamino]-3-methylbutanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(O)(C(C)C)C(N)=O)CCC(=O)N1C(CN2CCO)CC2C1 GRSGSWSMFLUWKY-UHFFFAOYSA-N 0.000 claims 1
- SRDRYTRKCQSMKY-UHFFFAOYSA-N acetamide;benzoic acid Chemical compound CC(N)=O.OC(=O)C1=CC=CC=C1 SRDRYTRKCQSMKY-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 239000007858 starting material Substances 0.000 description 36
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 108060005980 Collagenase Proteins 0.000 description 17
- 102000029816 Collagenase Human genes 0.000 description 17
- 229960002424 collagenase Drugs 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 16
- 239000003112 inhibitor Substances 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 239000000758 substrate Substances 0.000 description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
- 125000004494 ethyl ester group Chemical group 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 238000003556 assay Methods 0.000 description 12
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 12
- HDSKIPUGIPWRCI-UHFFFAOYSA-N methyl(piperidin-4-yl)carbamic acid Chemical compound OC(=O)N(C)C1CCNCC1 HDSKIPUGIPWRCI-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexylacetic acid Chemical compound OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 7
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 7
- 102000004142 Trypsin Human genes 0.000 description 7
- 108090000631 Trypsin Proteins 0.000 description 7
- 239000012588 trypsin Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 108091007196 stromelysin Proteins 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- NCQJBPXXRXOIJD-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-naphthalen-2-ylpropanoic acid Chemical compound C1=CC=CC2=CC(C(CC(O)=O)NC(=O)OC(C)(C)C)=CC=C21 NCQJBPXXRXOIJD-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 108010026132 Gelatinases Proteins 0.000 description 4
- 102000013382 Gelatinases Human genes 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 239000004677 Nylon Substances 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- OGKKORGKSRNYDJ-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium;fluoro(dioxido)borane Chemical compound [O-]B([O-])F.[O-]B([O-])F.[O-]B([O-])F.[O-]B([O-])F.[O-]B([O-])F.[O-]B([O-])F.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1.C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 OGKKORGKSRNYDJ-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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- C07—ORGANIC CHEMISTRY
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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US2467596P | 1996-08-23 | 1996-08-23 |
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HR (1) | HRP970453A2 (es) |
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IL (1) | IL128189A0 (es) |
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PE (1) | PE99698A1 (es) |
PL (1) | PL331895A1 (es) |
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1997
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EP0922030A1 (en) | 1999-06-16 |
AP9701078A0 (en) | 1997-10-31 |
EA199900139A1 (ru) | 1999-08-26 |
PA8435301A1 (es) | 1999-12-27 |
GT199700094A (es) | 1999-02-10 |
IS4958A (is) | 1999-01-26 |
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AU711585B2 (en) | 1999-10-14 |
OA10978A (en) | 2001-11-05 |
AU3456397A (en) | 1998-03-06 |
PL331895A1 (en) | 1999-08-16 |
AR009292A1 (es) | 2000-04-12 |
TW397823B (en) | 2000-07-11 |
TR199900387T2 (xx) | 1999-04-21 |
CA2264284A1 (en) | 1998-02-26 |
SK21499A3 (en) | 2000-05-16 |
JP2000501423A (ja) | 2000-02-08 |
IL128189A0 (en) | 1999-11-30 |
NO990821L (no) | 1999-02-23 |
ID18063A (id) | 1998-02-26 |
CO4600003A1 (es) | 1998-05-08 |
WO1998007697A1 (en) | 1998-02-26 |
MA24307A1 (fr) | 1998-04-01 |
PE99698A1 (es) | 1998-12-26 |
CN1228083A (zh) | 1999-09-08 |
TNSN97139A1 (fr) | 2005-03-15 |
ZA977561B (en) | 1999-02-22 |
BR9711223A (pt) | 1999-08-17 |
HN1997000110A (es) | 1998-02-26 |
NO990821D0 (no) | 1999-02-22 |
KR20000068248A (ko) | 2000-11-25 |
BG103191A (en) | 1999-11-30 |
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