HRP20010660A2 - Sulfamato hydroxamic acid metalloprotease inhibitor - Google Patents
Sulfamato hydroxamic acid metalloprotease inhibitor Download PDFInfo
- Publication number
- HRP20010660A2 HRP20010660A2 HR20010660A HRP20010660A HRP20010660A2 HR P20010660 A2 HRP20010660 A2 HR P20010660A2 HR 20010660 A HR20010660 A HR 20010660A HR P20010660 A HRP20010660 A HR P20010660A HR P20010660 A2 HRP20010660 A2 HR P20010660A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- group
- independently selected
- substituents
- amino
- Prior art date
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- 239000003475 metalloproteinase inhibitor Substances 0.000 title claims description 7
- 101000998548 Yersinia ruckeri Alkaline proteinase inhibitor Proteins 0.000 title claims description 6
- 239000002253 acid Substances 0.000 title description 26
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 title description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 319
- -1 alkoxy-heteroaryl Chemical group 0.000 claims description 268
- 125000001424 substituent group Chemical group 0.000 claims description 207
- 150000001875 compounds Chemical class 0.000 claims description 182
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 135
- 125000003118 aryl group Chemical group 0.000 claims description 126
- 125000001072 heteroaryl group Chemical group 0.000 claims description 102
- 125000000217 alkyl group Chemical group 0.000 claims description 92
- 229910052757 nitrogen Inorganic materials 0.000 claims description 82
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 77
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 74
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 74
- 150000003839 salts Chemical class 0.000 claims description 63
- 125000003342 alkenyl group Chemical group 0.000 claims description 60
- 125000001145 hydrido group Chemical group *[H] 0.000 claims description 59
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 56
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 48
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
- 125000000304 alkynyl group Chemical group 0.000 claims description 38
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 33
- 125000003435 aroyl group Chemical group 0.000 claims description 32
- 125000001188 haloalkyl group Chemical group 0.000 claims description 29
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 29
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 28
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 27
- 102000005741 Metalloproteases Human genes 0.000 claims description 25
- 108010006035 Metalloproteases Proteins 0.000 claims description 25
- 125000004104 aryloxy group Chemical group 0.000 claims description 25
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 25
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 24
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 24
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 24
- 102100026802 72 kDa type IV collagenase Human genes 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 108050005238 Collagenase 3 Proteins 0.000 claims description 21
- 102100027995 Collagenase 3 Human genes 0.000 claims description 21
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 21
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 21
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 20
- 230000002401 inhibitory effect Effects 0.000 claims description 20
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- 101710151806 72 kDa type IV collagenase Proteins 0.000 claims description 19
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 claims description 19
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 18
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 18
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 17
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 16
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 230000001575 pathological effect Effects 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 14
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 12
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 12
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 11
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 10
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 10
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 10
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 9
- 229910020008 S(O) Inorganic materials 0.000 claims description 9
- 150000001768 cations Chemical class 0.000 claims description 9
- 150000002825 nitriles Chemical class 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000000446 sulfanediyl group Chemical class *S* 0.000 claims description 9
- 150000003457 sulfones Chemical class 0.000 claims description 9
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 8
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 8
- 125000004171 alkoxy aryl group Chemical group 0.000 claims description 8
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 8
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 8
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical compound N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 239000011159 matrix material Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 8
- 150000003462 sulfoxides Chemical class 0.000 claims description 8
- 125000004950 trifluoroalkyl group Chemical group 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 claims description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000003627 8 membered carbocyclic group Chemical group 0.000 claims description 4
- 229920001774 Perfluoroether Polymers 0.000 claims description 4
- OXBOABAOQWBSIV-UHFFFAOYSA-N [N]S(N)(=O)=O Chemical compound [N]S(N)(=O)=O OXBOABAOQWBSIV-UHFFFAOYSA-N 0.000 claims description 4
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 4
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 4
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 4
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 4
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 4
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 claims description 4
- 238000010647 peptide synthesis reaction Methods 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 239000011347 resin Substances 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 449
- 239000000243 solution Substances 0.000 description 253
- 235000019439 ethyl acetate Nutrition 0.000 description 150
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 141
- 239000007787 solid Substances 0.000 description 139
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 137
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 130
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 130
- 238000002360 preparation method Methods 0.000 description 125
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 120
- 239000011541 reaction mixture Substances 0.000 description 107
- 239000007832 Na2SO4 Substances 0.000 description 100
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 100
- 229910052938 sodium sulfate Inorganic materials 0.000 description 100
- 235000011152 sodium sulphate Nutrition 0.000 description 100
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 97
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 87
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 78
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 235000002639 sodium chloride Nutrition 0.000 description 59
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 52
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 51
- 239000000203 mixture Substances 0.000 description 47
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 41
- 239000000047 product Substances 0.000 description 39
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 37
- 239000003921 oil Substances 0.000 description 35
- 235000019198 oils Nutrition 0.000 description 35
- 239000011780 sodium chloride Substances 0.000 description 34
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 32
- 229940124530 sulfonamide Drugs 0.000 description 32
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 31
- 239000002904 solvent Substances 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- 125000002252 acyl group Chemical group 0.000 description 29
- 150000003456 sulfonamides Chemical class 0.000 description 29
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- 230000008901 benefit Effects 0.000 description 27
- 230000005764 inhibitory process Effects 0.000 description 27
- 239000007858 starting material Substances 0.000 description 26
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 25
- 150000003254 radicals Chemical class 0.000 description 25
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- 239000002002 slurry Substances 0.000 description 25
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 24
- 238000004587 chromatography analysis Methods 0.000 description 24
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 23
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 23
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- 235000011181 potassium carbonates Nutrition 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 20
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- 238000004811 liquid chromatography Methods 0.000 description 19
- 102000004190 Enzymes Human genes 0.000 description 18
- 108090000790 Enzymes Proteins 0.000 description 18
- 229940088598 enzyme Drugs 0.000 description 18
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 17
- 239000003814 drug Substances 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 15
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 14
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 14
- 201000010099 disease Diseases 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 14
- NLXXVSKHVGDQAT-UHFFFAOYSA-N o-(oxan-2-yl)hydroxylamine Chemical compound NOC1CCCCO1 NLXXVSKHVGDQAT-UHFFFAOYSA-N 0.000 description 14
- 229910052700 potassium Inorganic materials 0.000 description 14
- 239000011591 potassium Substances 0.000 description 14
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 13
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 13
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 13
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 12
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 12
- GPKMZACUUQFPGH-UHFFFAOYSA-N C=NS(=O)=O Chemical compound C=NS(=O)=O GPKMZACUUQFPGH-UHFFFAOYSA-N 0.000 description 12
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 12
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 12
- 229910000024 caesium carbonate Inorganic materials 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 235000021395 porridge Nutrition 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 11
- UNNNAIWPDLRVRN-UHFFFAOYSA-N 1-fluoro-4-(trifluoromethyl)benzene Chemical compound FC1=CC=C(C(F)(F)F)C=C1 UNNNAIWPDLRVRN-UHFFFAOYSA-N 0.000 description 10
- 229940124761 MMP inhibitor Drugs 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 230000009471 action Effects 0.000 description 10
- 210000002808 connective tissue Anatomy 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 238000004949 mass spectrometry Methods 0.000 description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 102000003390 tumor necrosis factor Human genes 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- 230000008034 disappearance Effects 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 238000010626 work up procedure Methods 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- 102000029816 Collagenase Human genes 0.000 description 6
- 108060005980 Collagenase Proteins 0.000 description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 229940113088 dimethylacetamide Drugs 0.000 description 6
- 150000003840 hydrochlorides Chemical class 0.000 description 6
- 150000002500 ions Chemical group 0.000 description 6
- OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 6
- 229950008959 marimastat Drugs 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- FLKRMXAWABTWSH-UHFFFAOYSA-N piperidine-1-sulfonamide Chemical compound NS(=O)(=O)N1CCCCC1 FLKRMXAWABTWSH-UHFFFAOYSA-N 0.000 description 6
- 150000003053 piperidines Chemical class 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 5
- 102100030416 Stromelysin-1 Human genes 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 229960002424 collagenase Drugs 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000004533 oil dispersion Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 5
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
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- 125000001425 triazolyl group Chemical group 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D211/06—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
- 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D211/06—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
- 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- C07D211/66—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having a hetero atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/96—Sulfur atom
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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
- C07D295/22—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 with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings 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
- C07D309/10—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- 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
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- 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
- C07D405/14—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 three or more hetero rings
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Biomedical Technology (AREA)
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- Hospice & Palliative Care (AREA)
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- Immunology (AREA)
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- Ophthalmology & Optometry (AREA)
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- Hematology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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PCT/US2000/003061 WO2000046221A1 (en) | 1999-02-08 | 2000-02-07 | Sulfamato hydroxamic acid metalloprotease inhibitor |
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EP (1) | EP1157021A1 (hu) |
JP (1) | JP2002536373A (hu) |
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CN (1) | CN1216056C (hu) |
AP (1) | AP2001002240A0 (hu) |
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AU (1) | AU775701B2 (hu) |
BG (1) | BG105788A (hu) |
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CA (1) | CA2362230A1 (hu) |
CZ (1) | CZ20012849A3 (hu) |
EA (1) | EA005500B1 (hu) |
EE (1) | EE200100410A (hu) |
GE (1) | GEP20043238B (hu) |
HK (1) | HK1049660B (hu) |
HR (1) | HRP20010660A2 (hu) |
HU (1) | HUP0200119A3 (hu) |
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PL (1) | PL350193A1 (hu) |
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WO (1) | WO2000046221A1 (hu) |
YU (1) | YU57101A (hu) |
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Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6747027B1 (en) | 1996-07-22 | 2004-06-08 | Pharmacia Corporation | Thiol sulfonamide metalloprotease inhibitors |
US6794511B2 (en) | 1997-03-04 | 2004-09-21 | G. D. Searle | Sulfonyl aryl or heteroaryl hydroxamic acid compounds |
US6696449B2 (en) | 1997-03-04 | 2004-02-24 | Pharmacia Corporation | Sulfonyl aryl hydroxamates and their use as matrix metalloprotease inhibitors |
US7115632B1 (en) | 1999-05-12 | 2006-10-03 | G. D. Searle & Co. | Sulfonyl aryl or heteroaryl hydroxamic acid compounds |
CN1279669A (zh) | 1997-11-14 | 2001-01-10 | G·D·瑟尔公司 | 芳族砜异羟肟酸金属蛋白酶抑制剂 |
US6750228B1 (en) | 1997-11-14 | 2004-06-15 | Pharmacia Corporation | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
US20010039287A1 (en) * | 1997-11-14 | 2001-11-08 | Thomas E Barta | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
US6800646B1 (en) | 1999-02-08 | 2004-10-05 | Pharmacia Corporation | Sulfamato hydroxamic acid metalloprotease inhibitor |
US6511993B1 (en) | 1999-06-03 | 2003-01-28 | Kevin Neil Dack | Metalloprotease inhibitors |
US6683093B2 (en) | 2000-05-12 | 2004-01-27 | Pharmacia Corporation | Aromatic sulfone hydroxamic acids and their use as protease inhibitors |
HUP0304069A2 (hu) | 2001-05-11 | 2004-04-28 | Pharmacia Corp. | Aromás szulfon-hidroxamátok és proteázgátlókként való alkalmazásuk |
US6683078B2 (en) | 2001-07-19 | 2004-01-27 | Pharmacia Corporation | Use of sulfonyl aryl or heteroaryl hydroxamic acids and derivatives thereof as aggrecanase inhibitors |
GB0119396D0 (en) | 2001-08-09 | 2001-10-03 | Celltech R&D Ltd | Hydroxamic acid derivatives |
GB0119474D0 (en) * | 2001-08-09 | 2001-10-03 | Astrazeneca Ab | Compounds |
US7629343B2 (en) | 2002-04-03 | 2009-12-08 | Topotarget Uk Limited | Carbamic acid compounds comprising a piperazine linkage as HDAC inhibitors |
MXPA04010555A (es) * | 2002-04-25 | 2005-02-17 | Pharmacia Corp | Acidos piperidinil- y piperazinil-sulfonilmetil hidroxamicos y su uso como inhibidores de proteasa. |
US20050209278A1 (en) * | 2002-04-25 | 2005-09-22 | Mcdonald Joseph J | Piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids and their use as protease inhibitors |
JP2006502980A (ja) * | 2002-06-25 | 2006-01-26 | ファルマシア・コーポレーション | アリールスルホニルヒドロキサム酸およびアミド誘導体、ならびにプロテアーゼ阻害薬としてのそれらの使用 |
GB0216382D0 (en) * | 2002-07-13 | 2002-08-21 | Astrazeneca Ab | Compounds |
CA2506796A1 (en) * | 2002-11-25 | 2004-06-10 | Pharmacia Corporation | Heteroarylsulfonylmethyl hydroxamic acids and amides and their use as protease inhibitors |
EP1594459B1 (en) | 2002-12-30 | 2010-02-17 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
JP4612621B2 (ja) | 2003-01-17 | 2011-01-12 | トポターゲット ユーケー リミテッド | Hdac阻害剤としてのエステル又はケトン結合を含むカルバミン酸化合物 |
US20050043533A1 (en) * | 2003-03-25 | 2005-02-24 | Babiak Kevin A. | Process for making alpha-substituted hydroxamic acids |
GB0319069D0 (en) * | 2003-08-14 | 2003-09-17 | Glaxo Group Ltd | Therapeutically useful compounds |
EP1743638A1 (en) | 2005-07-15 | 2007-01-17 | Laboratorios Del Dr. Esteve, S.A. | Pharmaceutical formulations of substituted pyrazoline compounds |
AU2006327245A1 (en) * | 2005-12-21 | 2007-06-28 | Decode Genetics Ehf | Biaryl substituted nitrogen containing heterocycle inhibitors of LTA4H for treating inflammation |
AU2007334519A1 (en) * | 2006-12-14 | 2008-06-26 | Merck Sharp & Dohme Corp. | Acyl bipiperidinyl compounds, compositions containing such compounds and methods of treatment |
US8906334B2 (en) | 2007-05-14 | 2014-12-09 | Invista North America S.A R.L. | High efficiency reactor and process |
WO2013039851A1 (en) | 2011-09-12 | 2013-03-21 | Mallinckrodt Llc | Optical agents for imaging and visualization of matrix metalloproteinase enzymes |
WO2018037254A1 (en) * | 2016-08-24 | 2018-03-01 | Tfchem | Difluorinated compounds as depigmenting or lightening agents |
US11590226B2 (en) | 2018-06-29 | 2023-02-28 | Loyola University Of Chicago | Carborane hydroxamic acid matrix metalloproteinase inhibitors and agents for boron neutron capture therapy |
WO2020070239A1 (en) | 2018-10-04 | 2020-04-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Egfr inhibitors for treating keratodermas |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1067965A (en) | 1912-10-31 | 1913-07-22 | C T Ham Mfg Company | Vehicle-lamp. |
GB1067965A (en) * | 1965-01-22 | 1967-05-10 | Beecham Group Ltd | Penicillins, esters, amides and salts thereof |
US4595700A (en) | 1984-12-21 | 1986-06-17 | G. D. Searle & Co. | Thiol based collagenase inhibitors |
US4882434A (en) | 1986-10-29 | 1989-11-21 | Takeda Chemical Industries, Ltd. | Gamma-lactonecarboxylic acid derivatives and their use as antibacterial agents or intermediates |
DE3811777A1 (de) * | 1988-04-08 | 1989-10-19 | Hoechst Ag | Heterocyclisch substituierte alkyl- und alkenylsulfonylharnstoffe, verfahren zu ihrer herstellung und ihre verwendung als herbizide oder pflanzenwachstumsregulatoren |
GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
JP3122161B2 (ja) | 1991-05-16 | 2001-01-09 | 武田薬品工業株式会社 | γ−ラクトン免疫抑制剤 |
ATE150452T1 (de) | 1992-04-07 | 1997-04-15 | British Biotech Pharm | Hydroxamsäure enthaltende collagenase-inhibitoren und cytokinaktivitätsinhibitoren |
US5376664A (en) | 1992-07-27 | 1994-12-27 | The Du Pont Merck Pharmaceutical Company | Unsymmetrical mono-3-nitro bis-naphthalimides as anticancer agents |
US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
GB9307956D0 (en) | 1993-04-17 | 1993-06-02 | Walls Alan J | Hydroxamic acid derivatives |
GB9320660D0 (en) | 1993-10-07 | 1993-11-24 | British Bio Technology | Inhibition of cytokine production |
DE69423773T2 (de) | 1993-11-04 | 2000-07-20 | Liposome Co Inc | Behandlungsverfahren unter verwendung unilamellar-liposomaler arachiddonsäuremetabolit-formulierungen |
GB9323165D0 (en) | 1993-11-10 | 1994-01-05 | Chiros Ltd | Compounds |
GB9416897D0 (en) | 1994-08-20 | 1994-10-12 | British Biotech Pharm | Metalloproteinase inhibitors |
MX9702487A (es) | 1994-10-05 | 1998-04-30 | Darwin Discovery Ltd | Compuestos peptidilo y su uso terapeutico como inhibidores de las metaloproteasas. |
CZ292942B6 (cs) | 1995-12-08 | 2004-01-14 | Agouron Pharmaceuticals, Inc. | Derivát (N-hydroxykarbamoyl)-1-(4-fenoxy)benzensulfonylu |
DE69624081T2 (de) | 1995-12-20 | 2003-06-12 | Hoffmann La Roche | Matrix-metalloprotease Inhibitoren |
ATE262899T1 (de) | 1996-01-02 | 2004-04-15 | Aventis Pharma Inc | Substituierte (aryl, heteroaryl, arylmethyl oder heteroarylmethyl) hydroxamisaeureverbindungen |
ES2225980T3 (es) * | 1996-06-20 | 2005-03-16 | Schering Corporation | Naftridinas que afectan al receptor de il-4 y al g-csf. |
ZA98376B (en) * | 1997-01-23 | 1998-07-23 | Hoffmann La Roche | Sulfamide-metalloprotease inhibitors |
CA2282656A1 (en) * | 1997-02-27 | 1998-09-03 | American Cyanamid Company | N-hydroxy-2-(alkyl, aryl, or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors |
DE69811111T2 (de) * | 1997-11-12 | 2003-07-24 | Darwin Discovery Ltd | Hydroxamsäure- und carbonsäurederivate mit mmp und tnf hemmender wirkung |
US20010039287A1 (en) | 1997-11-14 | 2001-11-08 | Thomas E Barta | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
CN1279669A (zh) * | 1997-11-14 | 2001-01-10 | G·D·瑟尔公司 | 芳族砜异羟肟酸金属蛋白酶抑制剂 |
GB9725782D0 (en) * | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
IL127496A0 (en) | 1997-12-19 | 1999-10-28 | Pfizer Prod Inc | The use of MMP inhibitors for the treatment of ocular angiogenesis |
GB9801690D0 (en) * | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
TR200002423T2 (tr) | 1998-02-19 | 2001-01-22 | American Cyanamid Company | Matriks metaloproteinaz inhibatörler. |
KR20010109275A (ko) | 1998-12-23 | 2001-12-08 | 로저 에이. 윌리암스 | 종양치료의 병용치료로서 사이클로옥시게나제-2 억제제와기질 금속단백분해효소 억제제를 사용하는 방법 |
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- 2000-02-07 JP JP2000597291A patent/JP2002536373A/ja active Pending
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Also Published As
Publication number | Publication date |
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SK11352001A3 (sk) | 2002-09-10 |
KR20010102000A (ko) | 2001-11-15 |
AP2001002240A0 (en) | 2001-09-30 |
US6448250B1 (en) | 2002-09-10 |
PL350193A1 (en) | 2002-11-18 |
EP1157021A1 (en) | 2001-11-28 |
CZ20012849A3 (cs) | 2002-05-15 |
AU775701B2 (en) | 2004-08-12 |
IS6039A (is) | 2001-08-07 |
US6372758B1 (en) | 2002-04-16 |
CN1362954A (zh) | 2002-08-07 |
CA2362230A1 (en) | 2000-08-10 |
ZA200106492B (en) | 2003-05-07 |
WO2000046221A1 (en) | 2000-08-10 |
GEP20043238B (en) | 2004-05-25 |
BG105788A (bg) | 2002-02-28 |
HUP0200119A3 (en) | 2003-04-28 |
JP2002536373A (ja) | 2002-10-29 |
NO20013850L (no) | 2001-09-19 |
HK1049660A1 (en) | 2003-05-23 |
AR036585A1 (es) | 2004-09-22 |
NO20013850D0 (no) | 2001-08-07 |
EE200100410A (et) | 2002-12-16 |
US6492367B1 (en) | 2002-12-10 |
CN1216056C (zh) | 2005-08-24 |
BR0008440A (pt) | 2002-03-26 |
EA200100867A1 (ru) | 2002-04-25 |
HK1049660B (zh) | 2006-05-12 |
YU57101A (sh) | 2005-06-10 |
EA005500B1 (ru) | 2005-02-24 |
AU2757400A (en) | 2000-08-25 |
IL144783A0 (en) | 2002-06-30 |
MXPA01007987A (es) | 2002-04-24 |
HUP0200119A2 (en) | 2002-06-29 |
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