CA2216151A1 - Reversible protease inhibitors - Google Patents
Reversible protease inhibitors Download PDFInfo
- Publication number
- CA2216151A1 CA2216151A1 CA002216151A CA2216151A CA2216151A1 CA 2216151 A1 CA2216151 A1 CA 2216151A1 CA 002216151 A CA002216151 A CA 002216151A CA 2216151 A CA2216151 A CA 2216151A CA 2216151 A1 CA2216151 A1 CA 2216151A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- optionally substituted
- hydroxy
- hydrogen
- group
- 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
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title claims abstract description 11
- 230000002441 reversible effect Effects 0.000 title abstract description 12
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 196
- 239000003112 inhibitor Substances 0.000 claims abstract description 83
- 108010005843 Cysteine Proteases Proteins 0.000 claims abstract description 59
- 102000005927 Cysteine Proteases Human genes 0.000 claims abstract description 58
- -1 hydroxy, amino Chemical group 0.000 claims description 466
- 150000003254 radicals Chemical class 0.000 claims description 203
- 229910052739 hydrogen Inorganic materials 0.000 claims description 145
- 239000001257 hydrogen Substances 0.000 claims description 143
- 125000000217 alkyl group Chemical group 0.000 claims description 131
- 125000003118 aryl group Chemical group 0.000 claims description 126
- 239000000203 mixture Substances 0.000 claims description 114
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 87
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 79
- 150000002431 hydrogen Chemical group 0.000 claims description 69
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 67
- 150000003839 salts Chemical class 0.000 claims description 66
- 238000000034 method Methods 0.000 claims description 63
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 62
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 60
- 101000749287 Clitocybe nebularis Clitocypin Proteins 0.000 claims description 55
- 101000767029 Clitocybe nebularis Clitocypin-1 Proteins 0.000 claims description 55
- 229940094664 Cysteine protease inhibitor Drugs 0.000 claims description 55
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 55
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 54
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 51
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 49
- 125000003545 alkoxy group Chemical group 0.000 claims description 48
- 125000005843 halogen group Chemical group 0.000 claims description 48
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 46
- 229910052799 carbon Inorganic materials 0.000 claims description 45
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 45
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 42
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 41
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 38
- 239000004365 Protease Substances 0.000 claims description 32
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 30
- 125000001153 fluoro group Chemical group F* 0.000 claims description 28
- 125000001188 haloalkyl group Chemical group 0.000 claims description 28
- 102000035195 Peptidases Human genes 0.000 claims description 27
- 108091005804 Peptidases Proteins 0.000 claims description 27
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
- 125000001246 bromo group Chemical group Br* 0.000 claims description 24
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 24
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 24
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 230000005764 inhibitory process Effects 0.000 claims description 23
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 23
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 21
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 20
- 241001465754 Metazoa Species 0.000 claims description 19
- 125000003435 aroyl group Chemical group 0.000 claims description 18
- 230000027455 binding Effects 0.000 claims description 18
- 125000001624 naphthyl group Chemical group 0.000 claims description 17
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 15
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 15
- 239000011734 sodium Substances 0.000 claims description 15
- 229910052708 sodium Inorganic materials 0.000 claims description 15
- 125000005116 aryl carbamoyl group Chemical group 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 14
- 230000008685 targeting Effects 0.000 claims description 14
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 13
- 125000001041 indolyl group Chemical group 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000001544 thienyl group Chemical group 0.000 claims description 13
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 13
- 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 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 11
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 11
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 10
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 10
- 238000010494 dissociation reaction Methods 0.000 claims description 10
- 230000005593 dissociations Effects 0.000 claims description 10
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 7
- 101100240520 Caenorhabditis elegans nhr-14 gene Proteins 0.000 claims description 6
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 6
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 claims description 6
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims description 4
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 4
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 2
- 125000005647 linker group Chemical group 0.000 claims description 2
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 68
- 125000001589 carboacyl group Chemical group 0.000 claims 34
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 21
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims 9
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 116
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 98
- 239000000243 solution Substances 0.000 description 97
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- 238000003786 synthesis reaction Methods 0.000 description 69
- 230000015572 biosynthetic process Effects 0.000 description 67
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- 230000002829 reductive effect Effects 0.000 description 47
- 235000019439 ethyl acetate Nutrition 0.000 description 39
- 235000018417 cysteine Nutrition 0.000 description 38
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 38
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 37
- 239000002904 solvent Substances 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 239000002852 cysteine proteinase inhibitor Substances 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 229920006395 saturated elastomer Polymers 0.000 description 30
- 102000004190 Enzymes Human genes 0.000 description 29
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- 229940088598 enzyme Drugs 0.000 description 29
- 239000000047 product Substances 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- 239000000463 material Substances 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 24
- 150000001413 amino acids Chemical class 0.000 description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
- 235000001014 amino acid Nutrition 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 22
- 238000004809 thin layer chromatography Methods 0.000 description 22
- 150000001299 aldehydes Chemical class 0.000 description 21
- 239000002253 acid Substances 0.000 description 19
- 230000000875 corresponding effect Effects 0.000 description 19
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 17
- 239000000758 substrate Substances 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
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- 108090000765 processed proteins & peptides Proteins 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- 201000010099 disease Diseases 0.000 description 15
- 235000019419 proteases Nutrition 0.000 description 14
- 229910000104 sodium hydride Inorganic materials 0.000 description 14
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- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 13
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- 125000002252 acyl group Chemical group 0.000 description 12
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
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- 239000012312 sodium hydride Substances 0.000 description 8
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- 239000000816 peptidomimetic Substances 0.000 description 7
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- 239000004475 Arginine Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
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- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 6
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 6
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
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- 210000001519 tissue Anatomy 0.000 description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- 108090000624 Cathepsin L Proteins 0.000 description 5
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 102000005593 Endopeptidases Human genes 0.000 description 5
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- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- RYTMIGZBRFDNMS-UHFFFAOYSA-N sulfonylmethylphosphonic acid Chemical compound OP(O)(=O)C=S(=O)=O RYTMIGZBRFDNMS-UHFFFAOYSA-N 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- ITRMQOAUBNIWKS-SFHVURJKSA-N tert-butyl (4s)-4-amino-2-(4-nitrophenyl)-6-phenylhex-2-enoate Chemical compound C([C@H](N)C=C(C(=O)OC(C)(C)C)C=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 ITRMQOAUBNIWKS-SFHVURJKSA-N 0.000 description 1
- QPRWUHWUPPIRPY-ZMOHHVQKSA-N tert-butyl (e,3s)-3-amino-5-(benzenesulfonyl)pent-4-enoate;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.CC(C)(C)OC(=O)C[C@H](N)\C=C\S(=O)(=O)C1=CC=CC=C1 QPRWUHWUPPIRPY-ZMOHHVQKSA-N 0.000 description 1
- VUAFUTLGMQEWHT-RDRICISKSA-N tert-butyl (e,3s)-5-(benzenesulfonyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pent-4-enoate Chemical compound CC(C)(C)OC(=O)C[C@H](NC(=O)OC(C)(C)C)\C=C\S(=O)(=O)C1=CC=CC=C1 VUAFUTLGMQEWHT-RDRICISKSA-N 0.000 description 1
- PHQHBEJQNFAPBD-AWEZNQCLSA-N tert-butyl n-[(2s)-1-(chloromethylsulfonyl)-4-phenylbutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CS(=O)(=O)CCl)CCC1=CC=CC=C1 PHQHBEJQNFAPBD-AWEZNQCLSA-N 0.000 description 1
- SJODCYRYHPVMMQ-ZDUSSCGKSA-N tert-butyl n-[(2s)-1-hydroxy-4-phenylbutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CO)CCC1=CC=CC=C1 SJODCYRYHPVMMQ-ZDUSSCGKSA-N 0.000 description 1
- KCHWFNCWNONEJN-DAFXYXGESA-N tert-butyl n-[(2s)-4-phenyl-1-(1-trimethylsilylethylsulfonyl)butan-2-yl]carbamate Chemical compound C[Si](C)(C)C(C)S(=O)(=O)C[C@@H](NC(=O)OC(C)(C)C)CCC1=CC=CC=C1 KCHWFNCWNONEJN-DAFXYXGESA-N 0.000 description 1
- VKTQNTPOOJJEKC-SFHVURJKSA-N tert-butyl n-[(2s)-4-phenyl-1-(2-trimethylsilylethylsulfanyl)butan-2-yl]carbamate Chemical compound C[Si](C)(C)CCSC[C@@H](NC(=O)OC(C)(C)C)CCC1=CC=CC=C1 VKTQNTPOOJJEKC-SFHVURJKSA-N 0.000 description 1
- JZDHNVLREUDRPY-IBGZPJMESA-N tert-butyl n-[(3s)-1-(benzenesulfonyl)-5-phenylpentan-3-yl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)CCS(=O)(=O)C=1C=CC=CC=1)CC1=CC=CC=C1 JZDHNVLREUDRPY-IBGZPJMESA-N 0.000 description 1
- RHUSSAVCEINREK-UHFFFAOYSA-N tert-butyl n-[1-(benzenesulfonyl)-2-methylpropyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C(C)C)S(=O)(=O)C1=CC=CC=C1 RHUSSAVCEINREK-UHFFFAOYSA-N 0.000 description 1
- PBKUGOVQSDSWGT-CAIYBOLESA-N tert-butyl n-naphthalen-2-yl-n-[(2s)-1-[[(e,3s)-1-naphthalen-2-ylsulfonyl-5-phenylpent-1-en-3-yl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C([C@H](NC(=O)[C@@H](N(C(=O)OC(C)(C)C)C=1C=C2C=CC=CC2=CC=1)C)\C=C\S(=O)(=O)C=1C=C2C=CC=CC2=CC=1)CC1=CC=CC=C1 PBKUGOVQSDSWGT-CAIYBOLESA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000036964 tight binding Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- CIHAMXCDQQEGAE-UHFFFAOYSA-N trimethyl-[2-(2-trimethylsilylethylsulfanyl)ethyl]silane Chemical compound C[Si](C)(C)CCSCC[Si](C)(C)C CIHAMXCDQQEGAE-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/28—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/6533—Six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Enzymes And Modification Thereof (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40999695A | 1995-03-24 | 1995-03-24 | |
| US08/409,996 | 1995-03-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2216151A1 true CA2216151A1 (en) | 1996-10-03 |
Family
ID=23622800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002216151A Abandoned CA2216151A1 (en) | 1995-03-24 | 1996-03-21 | Reversible protease inhibitors |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0817778A1 (ko) |
| JP (1) | JPH11503417A (ko) |
| KR (1) | KR19980703261A (ko) |
| CN (1) | CN1071751C (ko) |
| AU (1) | AU713492B2 (ko) |
| CA (1) | CA2216151A1 (ko) |
| CZ (1) | CZ298197A3 (ko) |
| IL (1) | IL117638A0 (ko) |
| MY (1) | MY113489A (ko) |
| NO (1) | NO311573B1 (ko) |
| NZ (1) | NZ305626A (ko) |
| PL (1) | PL322409A1 (ko) |
| TW (1) | TW470750B (ko) |
| WO (1) | WO1996030353A1 (ko) |
| ZA (1) | ZA962336B (ko) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2251714A1 (en) | 1996-04-22 | 1997-10-30 | Massachusetts Institute Of Technology | Suppression of immune response via inhibition of cathepsin s |
| EP0934293A1 (en) * | 1996-07-30 | 1999-08-11 | Arris Pharmaceutical Corporation | Novel compounds and compositions for treating diseases associated with tryptase activity |
| DE19817461A1 (de) * | 1998-04-20 | 1999-10-21 | Basf Ag | Neue substituierte Benzamide, deren Herstellung und Anwendung |
| JP2002538151A (ja) | 1999-03-02 | 2002-11-12 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | カテプシンの可逆的インヒビターとして有用な化合物 |
| DE60003702T2 (de) * | 1999-09-13 | 2004-04-22 | Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield | Heterocyclische verbindungen als reversible inhibitoren von cysteinproteasen |
| US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
| CA2387805C (en) | 1999-11-18 | 2012-08-28 | Corvas International, Inc. | Nucleic acids encoding endotheliases, endotheliases and uses thereof |
| US7700341B2 (en) | 2000-02-03 | 2010-04-20 | Dendreon Corporation | Nucleic acid molecules encoding transmembrane serine proteases, the encoded proteins and methods based thereon |
| ATE324372T1 (de) | 2000-08-14 | 2006-05-15 | Ortho Mcneil Pharm Inc | Substituierte pyrazole |
| RU2317988C2 (ru) | 2000-08-14 | 2008-02-27 | Орто-Макнейл Фармасьютикал, Инк. | Замещенные пиразолы, фармацевтическая композиция на их основе, применение фармацевтической композиции и способ ингибирования активности катепсина s |
| PT1309591E (pt) | 2000-08-14 | 2007-04-30 | Ortho Mcneil Pharm Inc | Pirazoles substituídos |
| US7332494B2 (en) | 2000-08-14 | 2008-02-19 | Janssen Pharmaceutica, N.V. | Method for treating allergies using substituted pyrazoles |
| US6579896B2 (en) | 2000-09-06 | 2003-06-17 | Ortho-Mcneil Pharmaceutical, Inc. | Method for treating allergies using substituted pyrazoles |
| WO2002048097A1 (en) * | 2000-12-12 | 2002-06-20 | Corvas International, Inc. | Compounds, compositions and methods for treatment of parasitic infections |
| JP2004523506A (ja) | 2000-12-22 | 2004-08-05 | アクシス・ファーマシューティカルズ・インコーポレイテッド | カテプシン阻害剤としての新規な化合物と組成物 |
| US7030116B2 (en) | 2000-12-22 | 2006-04-18 | Aventis Pharmaceuticals Inc. | Compounds and compositions as cathepsin inhibitors |
| EP1436255A1 (en) * | 2001-09-14 | 2004-07-14 | Aventis Pharmaceuticals, Inc. | Novel compounds and compositions as cathepsin inhibitors |
| WO2003024923A1 (en) * | 2001-09-14 | 2003-03-27 | Axys Pharmaceuticals, Inc. | Sulfonamide compounds as protease inhibitors |
| KR20050044497A (ko) | 2001-11-14 | 2005-05-12 | 아벤티스 파마슈티칼스 인크. | 올리고펩티드 및 카텝신 ｓ 억제제로서 이를 포함하는조성물 |
| GB0311406D0 (en) * | 2003-05-17 | 2003-06-25 | Queen Mary & Westfield College | Substituted phosphonate fluorescent sensors,and use thereof |
| SG191591A1 (en) | 2008-05-21 | 2013-07-31 | New World Lab Inc | Selective caspase inhibitors and uses thereof |
| WO2010133000A1 (en) | 2009-05-21 | 2010-11-25 | New World Laboratories Inc. | Selective caspase inhibitors and uses thereof |
| US8895497B2 (en) | 2009-12-04 | 2014-11-25 | Dcb-Usa, Llc | Cathepsin S inhibitors |
| EP2697246B1 (en) | 2011-04-15 | 2018-03-07 | Genesis Technologies Limited | Selective cysteine protease inhibitors and uses thereof |
| KR101309578B1 (ko) * | 2011-05-06 | 2013-09-17 | 연세대학교 산학협력단 | 시스테인 프로테아제 선택성을 갖는 다이타이로신 화합물 및 이를 이용한 시스테인 프로테아제의 검출방법 |
| KR101385855B1 (ko) * | 2012-10-16 | 2014-04-22 | 이동익 | 카뎁신 검출용 다이아로마틱 아미노산 기질 |
| US20200361967A1 (en) * | 2018-01-19 | 2020-11-19 | Osaka Soda Co., Ltd. | Organosilicon compound and rubber composition comprising the same |
| EP3553521A1 (en) * | 2018-04-12 | 2019-10-16 | Koninklijke Philips N.V. | Gingivitis diagnostic methods, uses and kits |
-
1996
- 1996-03-21 AU AU53674/96A patent/AU713492B2/en not_active Ceased
- 1996-03-21 PL PL96322409A patent/PL322409A1/xx unknown
- 1996-03-21 CA CA002216151A patent/CA2216151A1/en not_active Abandoned
- 1996-03-21 JP JP8529509A patent/JPH11503417A/ja active Pending
- 1996-03-21 CZ CZ972981A patent/CZ298197A3/cs unknown
- 1996-03-21 NZ NZ305626A patent/NZ305626A/xx unknown
- 1996-03-21 EP EP96910499A patent/EP0817778A1/en not_active Withdrawn
- 1996-03-21 CN CN96193951A patent/CN1071751C/zh not_active Expired - Fee Related
- 1996-03-21 WO PCT/US1996/003844 patent/WO1996030353A1/en not_active Application Discontinuation
- 1996-03-21 KR KR1019970706665A patent/KR19980703261A/ko not_active Application Discontinuation
- 1996-03-22 MY MYPI96001076A patent/MY113489A/en unknown
- 1996-03-22 ZA ZA962336A patent/ZA962336B/xx unknown
- 1996-03-24 IL IL11763896A patent/IL117638A0/xx unknown
- 1996-04-12 TW TW085104392A patent/TW470750B/zh active
-
1997
- 1997-09-23 NO NO19974403A patent/NO311573B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| MY113489A (en) | 2002-03-30 |
| TW470750B (en) | 2002-01-01 |
| WO1996030353A1 (en) | 1996-10-03 |
| NZ305626A (en) | 2000-01-28 |
| CN1184472A (zh) | 1998-06-10 |
| EP0817778A1 (en) | 1998-01-14 |
| NO311573B1 (no) | 2001-12-10 |
| AU713492B2 (en) | 1999-12-02 |
| JPH11503417A (ja) | 1999-03-26 |
| CN1071751C (zh) | 2001-09-26 |
| AU5367496A (en) | 1996-10-16 |
| NO974403D0 (no) | 1997-09-23 |
| CZ298197A3 (cs) | 1998-03-18 |
| ZA962336B (en) | 1996-07-31 |
| NO974403L (no) | 1997-11-17 |
| PL322409A1 (en) | 1998-01-19 |
| IL117638A0 (en) | 1996-07-23 |
| KR19980703261A (ko) | 1998-10-15 |
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| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |