JP2001518081A - スルホニル2価アリールまたはヘテロアリールヒドロキサム酸化合物 - Google Patents
スルホニル2価アリールまたはヘテロアリールヒドロキサム酸化合物Info
- Publication number
- JP2001518081A JP2001518081A JP53879998A JP53879998A JP2001518081A JP 2001518081 A JP2001518081 A JP 2001518081A JP 53879998 A JP53879998 A JP 53879998A JP 53879998 A JP53879998 A JP 53879998A JP 2001518081 A JP2001518081 A JP 2001518081A
- Authority
- JP
- Japan
- Prior art keywords
- group
- hydrocarbyl
- ring
- aryl
- membered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 151
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 86
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 title claims abstract description 26
- -1 heteroaryl hydroxamic Chemical compound 0.000 title claims description 155
- 239000002253 acid Substances 0.000 title abstract description 69
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 51
- 230000000694 effects Effects 0.000 claims abstract description 29
- 102000005741 Metalloproteases Human genes 0.000 claims abstract description 24
- 108010006035 Metalloproteases Proteins 0.000 claims abstract description 24
- 230000001575 pathological effect Effects 0.000 claims abstract description 17
- 239000011159 matrix material Substances 0.000 claims abstract description 14
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims abstract description 9
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims abstract description 9
- 125000001424 substituent group Chemical group 0.000 claims description 73
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 60
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 43
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 18
- 239000003112 inhibitor Substances 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- 239000011593 sulfur Substances 0.000 claims description 18
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical group NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 125000003277 amino group Chemical group 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 150000004678 hydrides Chemical class 0.000 claims description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical group NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 9
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical group NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 5
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 241001024304 Mino Species 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 3
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000001769 aryl amino group Chemical group 0.000 claims description 2
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005419 heteroarylsulfonylamino group Chemical group 0.000 claims description 2
- 125000004476 heterocycloamino group Chemical group 0.000 claims description 2
- 125000004470 heterocyclooxy group Chemical group 0.000 claims description 2
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 2
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims 3
- 150000003857 carboxamides Chemical class 0.000 claims 2
- 229960001231 choline Drugs 0.000 claims 2
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- JURFKSPPIXXOMA-UHFFFAOYSA-N 2-(phenylcarbamoylamino)benzamide Chemical compound NC(=O)C1=CC=CC=C1NC(=O)NC1=CC=CC=C1 JURFKSPPIXXOMA-UHFFFAOYSA-N 0.000 claims 1
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 claims 1
- HXKWWDAWOMOFHB-UHFFFAOYSA-N 2-anilinopyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1NC1=CC=CC=C1 HXKWWDAWOMOFHB-UHFFFAOYSA-N 0.000 claims 1
- RNPHEKCWNBZQMV-UHFFFAOYSA-N 2-phenyldiazenylbenzamide Chemical compound NC(=O)C1=CC=CC=C1N=NC1=CC=CC=C1 RNPHEKCWNBZQMV-UHFFFAOYSA-N 0.000 claims 1
- BSGBIJQQYCHZQR-UHFFFAOYSA-N C1=CC=C(C=C1)N=NC2=C(C=CC(=C2OC3=CC=CS3)OC4=CC=CC=C4)C(=O)N Chemical compound C1=CC=C(C=C1)N=NC2=C(C=CC(=C2OC3=CC=CS3)OC4=CC=CC=C4)C(=O)N BSGBIJQQYCHZQR-UHFFFAOYSA-N 0.000 claims 1
- MVYCLNCRUKPZKM-UHFFFAOYSA-N C1=CC=C(C=C1)NC2=C(C=CC(=C2OC3=CC=CS3)C(=O)N)OC4=CC=CC=C4 Chemical compound C1=CC=C(C=C1)NC2=C(C=CC(=C2OC3=CC=CS3)C(=O)N)OC4=CC=CC=C4 MVYCLNCRUKPZKM-UHFFFAOYSA-N 0.000 claims 1
- 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims 1
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims 1
- WRGYTFATDFTUGF-QUKDMSEQSA-N n-[(2s,3s)-3-amino-1-phenylheptan-2-yl]-2-[methyl-[[(1s,2s)-2-methylcyclopropyl]methyl]amino]-6-[methylsulfonyl(propyl)amino]pyridine-4-carboxamide Chemical compound C([C@@H]([C@@H](N)CCCC)NC(=O)C=1C=C(N=C(C=1)N(C)C[C@@H]1[C@H](C1)C)N(CCC)S(C)(=O)=O)C1=CC=CC=C1 WRGYTFATDFTUGF-QUKDMSEQSA-N 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 17
- 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 abstract description 16
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 81
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 68
- 238000006243 chemical reaction Methods 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000003153 chemical reaction reagent Substances 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- 150000002148 esters Chemical class 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 23
- 150000003839 salts Chemical class 0.000 description 23
- 239000002585 base Substances 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 150000001412 amines Chemical class 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- 102000004190 Enzymes Human genes 0.000 description 18
- 108090000790 Enzymes Proteins 0.000 description 18
- 201000010099 disease Diseases 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 229940088598 enzyme Drugs 0.000 description 18
- 230000005764 inhibitory process Effects 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- 150000003457 sulfones Chemical class 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 239000011734 sodium Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 238000003756 stirring Methods 0.000 description 16
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 239000001257 hydrogen Substances 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 150000007513 acids Chemical class 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 14
- 229940024606 amino acid Drugs 0.000 description 14
- 125000004429 atom Chemical group 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 239000012141 concentrate Substances 0.000 description 14
- 235000008504 concentrate Nutrition 0.000 description 14
- 230000003647 oxidation Effects 0.000 description 14
- 238000007254 oxidation reaction Methods 0.000 description 14
- 150000003573 thiols Chemical class 0.000 description 14
- 108050005238 Collagenase 3 Proteins 0.000 description 13
- 102100027995 Collagenase 3 Human genes 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 239000000543 intermediate Substances 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 12
- 150000001413 amino acids Chemical class 0.000 description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 11
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 11
- 230000033115 angiogenesis Effects 0.000 description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 11
- 229910052751 metal Inorganic materials 0.000 description 11
- 239000002184 metal Substances 0.000 description 11
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 9
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 8
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- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 7
- 238000005804 alkylation reaction Methods 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 7
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
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- 102000029816 Collagenase Human genes 0.000 description 6
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
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- 239000011780 sodium chloride Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
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- 150000001298 alcohols Chemical class 0.000 description 5
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- 210000004087 cornea Anatomy 0.000 description 5
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- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 5
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Classifications
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/64—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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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
- 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
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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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- C07D213/82—Amides; Imides in position 3
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- 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
- C07D295/04—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 substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
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- Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3518297P | 1997-03-04 | 1997-03-04 | |
| US60/035,182 | 1997-03-04 | ||
| PCT/US1998/004300 WO1998038859A1 (en) | 1997-03-04 | 1998-03-04 | Sulfonyl divalent aryl or heteroaryl hydroxamic acid compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001518081A true JP2001518081A (ja) | 2001-10-09 |
| JP2001518081A5 JP2001518081A5 (enExample) | 2005-11-10 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP53879998A Abandoned JP2001518081A (ja) | 1997-03-04 | 1998-03-04 | スルホニル2価アリールまたはヘテロアリールヒドロキサム酸化合物 |
| JP53798598A Abandoned JP2002515900A (ja) | 1997-03-04 | 1998-03-04 | 芳香族スルホニルアルファ−ヒドロキシヒドロキサム酸化合物 |
| JP53878098A Abandoned JP2002515901A (ja) | 1997-03-04 | 1998-03-04 | 芳香族スルホニルα−シクロアミノヒドロキサム酸化合物 |
| JP53879698A Abandoned JP2002513407A (ja) | 1997-03-04 | 1998-03-04 | N−ヒドロキシ4−スルホニルブタンアミド化合物 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP53798598A Abandoned JP2002515900A (ja) | 1997-03-04 | 1998-03-04 | 芳香族スルホニルアルファ−ヒドロキシヒドロキサム酸化合物 |
| JP53878098A Abandoned JP2002515901A (ja) | 1997-03-04 | 1998-03-04 | 芳香族スルホニルα−シクロアミノヒドロキサム酸化合物 |
| JP53879698A Abandoned JP2002513407A (ja) | 1997-03-04 | 1998-03-04 | N−ヒドロキシ4−スルホニルブタンアミド化合物 |
Country Status (19)
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| EP (4) | EP0973392B1 (enExample) |
| JP (4) | JP2001518081A (enExample) |
| KR (3) | KR20000075946A (enExample) |
| CN (3) | CN1254337A (enExample) |
| AT (1) | ATE254599T1 (enExample) |
| AU (2) | AU750130B2 (enExample) |
| BR (2) | BR9808214A (enExample) |
| CA (4) | CA2282318A1 (enExample) |
| DE (1) | DE69819878T2 (enExample) |
| DK (1) | DK0973392T3 (enExample) |
| EA (1) | EA199900792A1 (enExample) |
| ES (2) | ES2206903T3 (enExample) |
| IL (3) | IL131494A (enExample) |
| NO (1) | NO315647B1 (enExample) |
| NZ (1) | NZ337326A (enExample) |
| PL (1) | PL335732A1 (enExample) |
| PT (1) | PT973392E (enExample) |
| WO (1) | WO1998038859A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005527556A (ja) * | 2002-04-03 | 2005-09-15 | トポターゲット ユーケー リミテッド | Hdac阻害剤としてのピペラジン結合を有するカルバミン酸化合物 |
| JP2008533137A (ja) * | 2005-03-16 | 2008-08-21 | アストラゼネカ・アクチエボラーグ | 好中球エラスターゼインヒビターとしての2−ピリジン誘導体 |
| JP2011079866A (ja) * | 2004-03-22 | 2011-04-21 | Southern Research Inst | マトリックスメタロプロテイナーゼの非ペプチドインヒビター |
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| US10531655B2 (en) | 2011-12-02 | 2020-01-14 | The Regents Of The University Of California | Reperfusion protection solution and uses thereof |
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-
1998
- 1998-03-04 CN CN98804628A patent/CN1254337A/zh active Pending
- 1998-03-04 KR KR1019997008028A patent/KR20000075946A/ko not_active Ceased
- 1998-03-04 DK DK98911481T patent/DK0973392T3/da active
- 1998-03-04 AT AT98911481T patent/ATE254599T1/de not_active IP Right Cessation
- 1998-03-04 EP EP98911481A patent/EP0973392B1/en not_active Expired - Lifetime
- 1998-03-04 EP EP98910177A patent/EP0984959B1/en not_active Expired - Lifetime
- 1998-03-04 AU AU65424/98A patent/AU750130B2/en not_active Ceased
- 1998-03-04 BR BR9808214-0A patent/BR9808214A/pt not_active IP Right Cessation
- 1998-03-04 JP JP53879998A patent/JP2001518081A/ja not_active Abandoned
- 1998-03-04 IL IL13149498A patent/IL131494A/xx not_active IP Right Cessation
- 1998-03-04 BR BR9808166-7A patent/BR9808166A/pt not_active Application Discontinuation
- 1998-03-04 CA CA002282318A patent/CA2282318A1/en not_active Abandoned
- 1998-03-04 EP EP98908949A patent/EP0983257A4/en not_active Withdrawn
- 1998-03-04 IL IL13149598A patent/IL131495A0/xx unknown
- 1998-03-04 ES ES98911481T patent/ES2206903T3/es not_active Expired - Lifetime
- 1998-03-04 DE DE69819878T patent/DE69819878T2/de not_active Expired - Fee Related
- 1998-03-04 WO PCT/US1998/004300 patent/WO1998038859A1/en not_active Ceased
- 1998-03-04 EA EA199900792A patent/EA199900792A1/ru unknown
- 1998-03-04 CN CN98804575A patent/CN1105114C/zh not_active Expired - Fee Related
- 1998-03-04 JP JP53798598A patent/JP2002515900A/ja not_active Abandoned
- 1998-03-04 PL PL98335732A patent/PL335732A1/xx unknown
- 1998-03-04 CN CN98804577A patent/CN1253474A/zh active Pending
- 1998-03-04 IL IL13149398A patent/IL131493A/en not_active IP Right Cessation
- 1998-03-04 NZ NZ337326A patent/NZ337326A/en unknown
- 1998-03-04 JP JP53878098A patent/JP2002515901A/ja not_active Abandoned
- 1998-03-04 ES ES98910177T patent/ES2209122T3/es not_active Expired - Lifetime
- 1998-03-04 KR KR1019997008036A patent/KR20000075954A/ko not_active Ceased
- 1998-03-04 KR KR1019997008037A patent/KR20000075955A/ko not_active Ceased
- 1998-03-04 CA CA002283145A patent/CA2283145A1/en not_active Abandoned
- 1998-03-04 PT PT98911481T patent/PT973392E/pt unknown
- 1998-03-04 EP EP98908964A patent/EP0983258A4/en not_active Withdrawn
- 1998-03-04 JP JP53879698A patent/JP2002513407A/ja not_active Abandoned
- 1998-03-04 CA CA002283272A patent/CA2283272A1/en not_active Abandoned
- 1998-03-04 CA CA002283275A patent/CA2283275A1/en not_active Abandoned
- 1998-03-04 AU AU66865/98A patent/AU750303B2/en not_active Ceased
- 1998-03-04 US US09/230,209 patent/US6380258B2/en not_active Expired - Fee Related
-
1999
- 1999-09-02 NO NO19994252A patent/NO315647B1/no unknown
-
2001
- 2001-11-29 US US09/997,552 patent/US6656954B2/en not_active Expired - Fee Related
-
2003
- 2003-10-27 US US10/695,278 patent/US20040097487A1/en not_active Abandoned
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005527556A (ja) * | 2002-04-03 | 2005-09-15 | トポターゲット ユーケー リミテッド | Hdac阻害剤としてのピペラジン結合を有するカルバミン酸化合物 |
| JP2011079866A (ja) * | 2004-03-22 | 2011-04-21 | Southern Research Inst | マトリックスメタロプロテイナーゼの非ペプチドインヒビター |
| JP2008533137A (ja) * | 2005-03-16 | 2008-08-21 | アストラゼネカ・アクチエボラーグ | 好中球エラスターゼインヒビターとしての2−ピリジン誘導体 |
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