JP2002515901A - 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 - Google Patents
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Info
- Publication number
- JP2002515901A JP2002515901A JP53878098A JP53878098A JP2002515901A JP 2002515901 A JP2002515901 A JP 2002515901A JP 53878098 A JP53878098 A JP 53878098A JP 53878098 A JP53878098 A JP 53878098A JP 2002515901 A JP2002515901 A JP 2002515901A
- Authority
- JP
- Japan
- Prior art keywords
- group
- hydrocarbyl
- compound
- aryl
- heteroaryl
- 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 133
- 239000002253 acid Substances 0.000 title abstract description 70
- 238000000034 method Methods 0.000 claims abstract description 47
- 102000005741 Metalloproteases Human genes 0.000 claims abstract description 24
- 108010006035 Metalloproteases Proteins 0.000 claims abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
- 201000010099 disease Diseases 0.000 claims abstract description 20
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims abstract description 18
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims abstract description 18
- 230000001575 pathological effect Effects 0.000 claims abstract description 16
- 239000011159 matrix material Substances 0.000 claims abstract description 12
- -1 heterocyclo Chemical group 0.000 claims description 269
- 125000001424 substituent group Chemical group 0.000 claims description 82
- 125000003118 aryl group Chemical group 0.000 claims description 57
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
- 125000001072 heteroaryl group Chemical group 0.000 claims description 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 230000000694 effects Effects 0.000 claims description 22
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 17
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical group NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 16
- 125000003277 amino group Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 claims description 13
- 150000004678 hydrides Chemical class 0.000 claims description 12
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical group NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 11
- 150000001408 amides Chemical class 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 125000005336 allyloxy group Chemical group 0.000 claims description 7
- 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 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 claims description 6
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
- 150000003857 carboxamides Chemical class 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 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 description 4
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 4
- 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 4
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 3
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 2
- 241001024304 Mino Species 0.000 claims description 2
- 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims description 2
- 125000001769 aryl amino group Chemical group 0.000 claims description 2
- 125000004658 aryl carbonyl 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
- 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
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims 4
- UEIZUEWXLJOVLD-UHFFFAOYSA-N 3-(1-methylpyrrolidin-3-yl)pyridine Chemical compound C1N(C)CCC1C1=CC=CN=C1 UEIZUEWXLJOVLD-UHFFFAOYSA-N 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 239000010979 ruby Substances 0.000 claims 2
- 229910001750 ruby Inorganic materials 0.000 claims 2
- QUVJQSPCNYDKEI-UHFFFAOYSA-N (3-acetamido-4-hydroxyphenyl)arsonic acid;methyl 1-methyl-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound COC(=O)C1=CCCN(C)C1.CC(=O)NC1=CC([As](O)(O)=O)=CC=C1O QUVJQSPCNYDKEI-UHFFFAOYSA-N 0.000 claims 1
- 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
- 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
- OAECMYYWWGHUQM-UHFFFAOYSA-N 3-anilinopyridine-4-carboxamide Chemical compound NC(=O)C1=CC=NC=C1NC1=CC=CC=C1 OAECMYYWWGHUQM-UHFFFAOYSA-N 0.000 claims 1
- WLAYMFZFUBRZIV-UHFFFAOYSA-N C1=CC=C(C=C1)NC2=C(C=C(C(=C2OC3=CC=CS3)N=NC4=CC=CC=C4)C(=O)N)OC5=CC=CC=C5 Chemical compound C1=CC=C(C=C1)NC2=C(C=C(C(=C2OC3=CC=CS3)N=NC4=CC=CC=C4)C(=O)N)OC5=CC=CC=C5 WLAYMFZFUBRZIV-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
- 241000790917 Dioxys <bee> Species 0.000 claims 1
- 241001553014 Myrsine salicina Species 0.000 claims 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims 1
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims 1
- 125000001288 lysyl group Chemical group 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
- 239000003595 mist Substances 0.000 claims 1
- 230000009471 action Effects 0.000 abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
- 239000000243 solution Substances 0.000 description 154
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 87
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
- 238000006243 chemical reaction Methods 0.000 description 85
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 239000000203 mixture Substances 0.000 description 39
- 229920006395 saturated elastomer Polymers 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 36
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 239000002904 solvent Substances 0.000 description 31
- 239000007787 solid Substances 0.000 description 30
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 29
- 150000003839 salts Chemical class 0.000 description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 229910001868 water Inorganic materials 0.000 description 27
- 239000002585 base Substances 0.000 description 24
- 150000001412 amines Chemical class 0.000 description 23
- 230000015572 biosynthetic process Effects 0.000 description 23
- 239000003153 chemical reaction reagent Substances 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 22
- 239000003921 oil Substances 0.000 description 22
- 235000019198 oils Nutrition 0.000 description 22
- 239000011734 sodium Substances 0.000 description 21
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 21
- 150000002148 esters Chemical class 0.000 description 20
- 150000007942 carboxylates Chemical class 0.000 description 19
- 235000019441 ethanol Nutrition 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- 102000004190 Enzymes Human genes 0.000 description 18
- 108090000790 Enzymes Proteins 0.000 description 18
- 229940024606 amino acid Drugs 0.000 description 18
- 229940088598 enzyme Drugs 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- 150000007513 acids Chemical class 0.000 description 17
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 17
- 230000002401 inhibitory effect Effects 0.000 description 17
- 150000001413 amino acids Chemical class 0.000 description 16
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 16
- 239000001257 hydrogen Substances 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 239000003112 inhibitor Substances 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 229910052751 metal Inorganic materials 0.000 description 13
- 239000002184 metal Substances 0.000 description 13
- 150000003573 thiols Chemical class 0.000 description 13
- 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 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 125000004429 atom Chemical group 0.000 description 12
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- 239000012141 concentrate Substances 0.000 description 12
- 235000008504 concentrate Nutrition 0.000 description 12
- 150000003457 sulfones Chemical class 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 11
- 125000002252 acyl group Chemical group 0.000 description 11
- 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 11
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000007254 oxidation reaction Methods 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 9
- 230000033115 angiogenesis Effects 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
- 150000002497 iodine compounds Chemical class 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 229940124761 MMP inhibitor Drugs 0.000 description 8
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 8
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
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- 238000006722 reduction reaction Methods 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 8
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical class C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000000010 aprotic solvent Substances 0.000 description 7
- 125000003710 aryl alkyl group Chemical group 0.000 description 7
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 7
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- 239000011591 potassium Substances 0.000 description 7
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- 239000000741 silica gel Substances 0.000 description 7
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- 238000006467 substitution reaction Methods 0.000 description 7
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- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 7
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- 238000005406 washing Methods 0.000 description 7
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 6
- VUFOTXYLUWEYFC-UHFFFAOYSA-N 4-phenoxybenzenethiol Chemical compound C1=CC(S)=CC=C1OC1=CC=CC=C1 VUFOTXYLUWEYFC-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102000029816 Collagenase Human genes 0.000 description 6
- 108060005980 Collagenase Proteins 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 229960002424 collagenase Drugs 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000004007 reversed phase HPLC Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000003570 air Substances 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
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- KUDVCIJWMSSMMD-UHFFFAOYSA-M sodium;4-phenoxybenzenethiolate Chemical compound [Na+].C1=CC([S-])=CC=C1OC1=CC=CC=C1 KUDVCIJWMSSMMD-UHFFFAOYSA-M 0.000 description 1
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- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- 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
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- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
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- 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
- C07C323/65—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 containing sulfur atoms of sulfone or sulfoxide groups bound to the 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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-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—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
- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- 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
- C07D295/04—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
- C07D295/15—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 to an acyclic saturated chain
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Oncology (AREA)
- Nutrition Science (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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/US1998/004273 WO1998039315A1 (en) | 1997-03-04 | 1998-03-04 | Aromatic sulfonyl alpha-cycloamino hydroxamic acid compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002515901A true JP2002515901A (ja) | 2002-05-28 |
Family
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| Application Number | Title | Priority Date | Filing Date |
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| 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 |
|---|---|---|---|
| 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 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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)
| Country | Link |
|---|---|
| US (3) | US6380258B2 (enExample) |
| 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) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5478499B2 (ja) * | 2008-10-27 | 2014-04-23 | 田辺三菱製薬株式会社 | 新規アミド誘導体およびその医薬としての用途 |
| JP2017515848A (ja) * | 2014-05-14 | 2017-06-15 | ザ リージェント オブ ザ ユニバーシティー オブ コロラド、ア ボディー コーポレート | タンパク質脱アセチル化酵素阻害剤およびタンパク質脱アセチル化酵素−タンパク質キナーゼ二重阻害剤としての複素環式ヒドロキサム酸ならびにその使用方法 |
| JP2023002688A (ja) * | 2016-03-17 | 2023-01-10 | ゼニオプロ ゲーエムベーハー | NotchシグナリングのエンハンサーならびにNotchのアップレギュレーションにより治療可能ながんおよび悪性腫瘍の治療におけるその使用 |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6747027B1 (en) | 1996-07-22 | 2004-06-08 | Pharmacia Corporation | Thiol sulfonamide metalloprotease inhibitors |
| US7115632B1 (en) | 1999-05-12 | 2006-10-03 | G. D. Searle & Co. | 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 |
| CN1254337A (zh) | 1997-03-04 | 2000-05-24 | 孟山都公司 | N-羟基4-磺酰基丁酰胺化合物 |
| US6794511B2 (en) | 1997-03-04 | 2004-09-21 | G. D. Searle | Sulfonyl aryl or heteroaryl hydroxamic acid compounds |
| TR200001391T2 (tr) * | 1997-11-21 | 2000-11-21 | Pharmacia & Upjohn Company | Matris metaloproteinaz önleyicileri olarak beta-sülfonil hidroksamik asitlerin alfa-hidroksi, -amino ve halo türevleri. |
| WO2000037433A1 (en) * | 1998-12-18 | 2000-06-29 | Abbott Laboratories | Inhibitors of matrix metalloproteinases |
| US6800646B1 (en) | 1999-02-08 | 2004-10-05 | Pharmacia Corporation | Sulfamato hydroxamic acid metalloprotease inhibitor |
| JP2003525203A (ja) | 1999-03-22 | 2003-08-26 | ダーウィン・ディスカバリー・リミテッド | ヒドロキサムおよびカルボン酸誘導体 |
| CA2373500A1 (en) * | 1999-05-12 | 2000-11-23 | G.D. Searle & Co. | Hydroxamic acid derivatives as matrix metalloprotease inhibitors |
| US6808902B1 (en) | 1999-11-12 | 2004-10-26 | Amgen Inc. | Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules |
| KR20070053362A (ko) | 1999-11-23 | 2007-05-23 | 메틸진, 인크. | 히스톤 디아세틸라제의 억제제 |
| NZ525439A (en) | 2000-09-29 | 2004-11-26 | Topotarget Uk Ltd | Carbamic acid compounds comprising a sulfonamide linkage as HDAC inhibitors |
| EP1335898B1 (en) | 2000-09-29 | 2005-11-23 | TopoTarget UK Limited | Carbamic acid compounds comprising an amide linkage as hdac inhibitors |
| NZ530765A (en) | 2001-06-26 | 2006-11-30 | Amgen Fremont Inc | Antibodies that bind OPGL and compositions and methods for the treatment of bone diseases |
| US6683078B2 (en) | 2001-07-19 | 2004-01-27 | Pharmacia Corporation | Use of sulfonyl aryl or heteroaryl hydroxamic acids and derivatives thereof as aggrecanase inhibitors |
| FR2827859B1 (fr) | 2001-07-30 | 2005-09-23 | Lipha | Derives 4-(arylthio) - ou 4-(heteroarylthio) -butyrique dans la preparation de medicaments destines au traitement du diabete |
| EP1492534B1 (en) | 2002-04-03 | 2008-06-25 | TopoTarget UK Limited | Carbamic acid compounds comprising a piperazine linkage as hdac inhibitors |
| BR0309671A (pt) | 2002-04-25 | 2005-05-03 | Pharmacia Corp | ácidos de piperidinil- e piperazinil-sulfonilmetil hidroxâmicos e seu uso como inibidores de protease |
| GB0226855D0 (en) * | 2002-11-18 | 2002-12-24 | Queen Mary & Westfield College | Histone deacetylase inhibitors |
| ATE457716T1 (de) | 2002-12-30 | 2010-03-15 | Angiotech Int Ag | Wirkstofffreisetzung von schnell gelierender polymerzusammensetzung |
| ES2537514T3 (es) | 2003-04-04 | 2015-06-09 | Incyte Corporation | Composiciones, métodos y kits relacionados con la escisión de HER-2 |
| US7262318B2 (en) * | 2004-03-10 | 2007-08-28 | Pfizer, Inc. | Substituted heteroaryl- and phenylsulfamoyl compounds |
| US8129406B2 (en) * | 2004-03-22 | 2012-03-06 | Southern Research Institute | Nonpeptide inhibitors of matrix metalloproteinases |
| WO2005117882A2 (en) * | 2004-04-20 | 2005-12-15 | Incyte Corporation | Hydroxamic acid derivatives as metalloprotease inhibitors |
| WO2006004598A2 (en) * | 2004-06-01 | 2006-01-12 | The Scripps Research Institute | Proteomic analysis |
| US20050277897A1 (en) * | 2004-06-14 | 2005-12-15 | Ghannoum Ziad R | Handpiece tip |
| TW200700392A (en) * | 2005-03-16 | 2007-01-01 | Astrazeneca Ab | Novel compounds |
| CN101273013B (zh) * | 2005-09-27 | 2013-06-12 | 盐野义制药株式会社 | 具有pgd2受体拮抗活性的磺酰胺衍生物 |
| AU2010303270A1 (en) | 2009-10-09 | 2012-05-03 | Zafgen Corporation | Sulphone compounds for use in the treatment of obesity |
| WO2012012642A1 (en) | 2010-07-22 | 2012-01-26 | Zafgen Corporation | Tricyclic compounds and methds of making and using same |
| WO2012103333A1 (en) | 2011-01-26 | 2012-08-02 | Zafgen Corporation | Tetrazole compounds and methods of making and using same |
| BR112013028665A2 (pt) | 2011-05-06 | 2016-09-06 | Zafgen Inc | compostos de sulfonamida tricíclicos e métodos para fazer e usar os mesmos |
| US9290472B2 (en) | 2011-05-06 | 2016-03-22 | Zafgen, Inc. | Partially saturated tricyclic compounds and methods of making and using same |
| CN103764652B (zh) | 2011-05-06 | 2016-03-23 | 扎夫根股份有限公司 | 三环吡唑磺酰胺化合物及其制备和使用方法 |
| CN102898332B (zh) * | 2011-07-25 | 2015-05-06 | 中国医学科学院医药生物技术研究所 | 一种异羟肟酸类衍生物、其药物组合物、制备方法及用途 |
| US10531655B2 (en) | 2011-12-02 | 2020-01-14 | The Regents Of The University Of California | Reperfusion protection solution and uses thereof |
| CA2861381A1 (en) | 2012-01-18 | 2013-07-25 | Zafgen, Inc. | Tricyclic sulfone compounds and methods of making and using same |
| CA2861390A1 (en) | 2012-01-18 | 2013-07-25 | Zafgen, Inc. | Tricyclic sulfonamide compounds and methods of making and using same |
| KR20150080614A (ko) | 2012-11-05 | 2015-07-09 | 자프겐 인크. | 비만의 치료 및/또는 제어에서 사용하기 위한 트리시클릭 화합물 |
| MX2015005732A (es) | 2012-11-05 | 2015-12-16 | Zafgen Inc | Compuestos tricíclicos y métodos para hacer y utilizar los mismos. |
| NZ707773A (en) | 2012-11-05 | 2019-05-31 | Zafgen Inc | Methods of treating liver diseases |
| WO2014072214A1 (en) * | 2012-11-09 | 2014-05-15 | Unilever N.V. | A composition and method for treating substrates |
| WO2020006384A1 (en) * | 2018-06-29 | 2020-01-02 | Loyola University Of Chicago | Carborane hydroxamic acid matrix metalloproteinase inhibitors and agents for boron neutron capture therapy |
| CN111217722B (zh) * | 2020-03-06 | 2024-01-02 | 华东理工大学 | 偶氮芳基脲类衍生物及其制备方法和应用 |
| CN116102391B (zh) * | 2023-01-06 | 2025-01-28 | 湖大粤港澳大湾区创新研究院(广州增城) | 二硫转移试剂及其合成与应用 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4148801A (en) | 1978-07-03 | 1979-04-10 | American Home Products Corporation | 3-[(Chlorophenylsulfonyl)methyl]-1,2,4-oxadiazole-5-carboxylic acid derivatives |
| US4595700A (en) | 1984-12-21 | 1986-06-17 | G. D. Searle & Co. | Thiol based collagenase inhibitors |
| US5103014A (en) | 1987-09-30 | 1992-04-07 | American Home Products Corporation | Certain 3,3'-[[[(2-phenyl-4-thiazolyl)methoxy]phenyl]methylene]dithiobis-propanoic acid derivatives |
| GB2212153B (en) | 1987-11-16 | 1992-01-15 | Squibb & Sons Inc | Phenyl hydroxamic acids |
| GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| US5527945A (en) * | 1989-02-10 | 1996-06-18 | Basf Aktiengesellschaft | Diphenylheteroalkyl derivatives, the preparation thereof and drugs and cosmetics prepared therefrom |
| DK0493925T3 (da) * | 1990-12-17 | 1998-07-27 | Sankyo Co | Pyrazolderivater med herbicid aktivitet, deres fremstilling og anvendelse |
| EP0634998B1 (en) | 1992-04-07 | 1997-03-19 | British Biotech Pharmaceuticals Limited | Hydroxamic acid based collagenase and cytokine inhibitors |
| US5376664A (en) | 1992-07-27 | 1994-12-27 | The Du Pont Merck Pharmaceutical Company | Unsymmetrical mono-3-nitro bis-naphthalimides as anticancer agents |
| US5506242A (en) | 1993-01-06 | 1996-04-09 | Ciba-Geigy Corporation | Arylsufonamido-substituted hydroxamic acids |
| US5455258A (en) * | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5552419A (en) | 1993-01-06 | 1996-09-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5646167A (en) | 1993-01-06 | 1997-07-08 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamix 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 |
| GB9323165D0 (en) | 1993-11-10 | 1994-01-05 | Chiros Ltd | Compounds |
| AU2394795A (en) | 1994-04-28 | 1995-11-29 | Du Pont Merck Pharmaceutical Company, The | Hydroxamic acid and amino acid derivatives and their use as anti-arthritic agents |
| GB9416897D0 (en) | 1994-08-20 | 1994-10-12 | British Biotech Pharm | Metalloproteinase inhibitors |
| CZ288436B6 (en) | 1994-10-05 | 2001-06-13 | Darwin Discovery Ltd | Peptidyl derivatives, their therapeutic use as inhibitors of metalloproteinases and pharmaceutical preparation in which they are comprised |
| US5789434A (en) * | 1994-11-15 | 1998-08-04 | Bayer Corporation | Derivatives of substituted 4-biarylbutyric acid as matrix metalloprotease inhibitors |
| IL138027A (en) | 1995-12-08 | 2004-08-31 | Agouron Pharma | Intermediates for the preparation and preparation of metalloproteinase inhibitors |
| DE69624081T2 (de) * | 1995-12-20 | 2003-06-12 | Agouron Pharmaceuticals, Inc. | Matrix-metalloprotease Inhibitoren |
| PT871439E (pt) * | 1996-01-02 | 2004-08-31 | Aventis Pharma Inc | Compostos do acido hidroxamico substituidos (arilo heteroarilo arilmetilo ou heteroarilmetilo) |
| WO1997049679A1 (en) | 1996-06-27 | 1997-12-31 | Ono Pharmaceutical Co., Ltd. | Aryl (sulfide, sulfoxide and sulfone) derivatives and drugs containing the same as the active ingredient |
| CA2263154A1 (en) * | 1996-08-07 | 1998-02-12 | Darwin Discovery Limited | Hydroxamic and carboxylic acid derivatives having mmp and tnf inhibitory activity |
| NZ334729A (en) * | 1996-09-27 | 2001-01-26 | Upjohn Co | 'Beta'-sulfonyl hydroxamic acids as matrix metalloproteinase inhibitors involved in tissue degradation |
| ATE205306T1 (de) * | 1997-01-13 | 2001-09-15 | Fuji Photo Film Co Ltd | Wärmeentwickelbares, photoempfindliches farbmaterial |
| AU5493598A (en) * | 1997-02-07 | 1998-08-26 | Pfizer Inc. | N-hydroxy-beta-sulfonyl-propionamide derivatives and their use as inhibitors of matrix metalloproteinases |
| EE04295B1 (et) * | 1997-02-27 | 2004-06-15 | American Cyanamid Company | N-hüdroksü-2-(alküül-, arüül- või heteroarüülsulfanüül-, -sulfinüül- või-sulfonüül-)-3-asendatud-alküülamiidid, -arüülamiidid või -heteroarüülamiididkui maatriksmetalloproteinaasi inhibiitorid |
| CN1254337A (zh) | 1997-03-04 | 2000-05-24 | 孟山都公司 | N-羟基4-磺酰基丁酰胺化合物 |
| US20010014688A1 (en) * | 1997-11-14 | 2001-08-16 | Thomas E. Barta | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
-
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 |
|---|---|---|---|---|
| JP5478499B2 (ja) * | 2008-10-27 | 2014-04-23 | 田辺三菱製薬株式会社 | 新規アミド誘導体およびその医薬としての用途 |
| JP2017515848A (ja) * | 2014-05-14 | 2017-06-15 | ザ リージェント オブ ザ ユニバーシティー オブ コロラド、ア ボディー コーポレート | タンパク質脱アセチル化酵素阻害剤およびタンパク質脱アセチル化酵素−タンパク質キナーゼ二重阻害剤としての複素環式ヒドロキサム酸ならびにその使用方法 |
| JP2023002688A (ja) * | 2016-03-17 | 2023-01-10 | ゼニオプロ ゲーエムベーハー | NotchシグナリングのエンハンサーならびにNotchのアップレギュレーションにより治療可能ながんおよび悪性腫瘍の治療におけるその使用 |
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