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
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
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- 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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WO1995035275A1 (en) * | 1994-06-22 | 1995-12-28 | British Biotech Pharmaceuticals Limited | Metalloproteinase inhibitors |
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US5994351A (en) * | 1998-07-27 | 1999-11-30 | Pfizer Inc. | Arylsulfonylamino hydroxamic acid derivatives |
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SK21499A3 (en) | 2000-05-16 |
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EA199900139A1 (ru) | 1999-08-26 |
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