JPS61143325A - 新規化合物、その製法及びそれを含む医薬組成物 - Google Patents
新規化合物、その製法及びそれを含む医薬組成物Info
- Publication number
- JPS61143325A JPS61143325A JP60269207A JP26920785A JPS61143325A JP S61143325 A JPS61143325 A JP S61143325A JP 60269207 A JP60269207 A JP 60269207A JP 26920785 A JP26920785 A JP 26920785A JP S61143325 A JPS61143325 A JP S61143325A
- Authority
- JP
- Japan
- Prior art keywords
- bis
- polyethylene glycol
- human
- acid
- 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.)
- Pending
Links
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- 229940088598 enzyme Drugs 0.000 claims description 58
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- 229940012957 plasmin Drugs 0.000 claims description 33
- -1 N-6-[N'-carbonylamino]hexylanthranilic acid Chemical compound 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 229920001223 polyethylene glycol Polymers 0.000 claims description 20
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 19
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 19
- 239000002202 Polyethylene glycol Substances 0.000 claims description 17
- 230000000903 blocking effect Effects 0.000 claims description 17
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- 229960000187 tissue plasminogen activator Drugs 0.000 claims description 17
- 239000003527 fibrinolytic agent Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 229940057847 polyethylene glycol 600 Drugs 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229940093430 polyethylene glycol 1500 Drugs 0.000 claims description 8
- 125000005647 linker group Chemical group 0.000 claims description 7
- 229910052757 nitrogen Chemical group 0.000 claims description 7
- 239000005711 Benzoic acid Substances 0.000 claims description 6
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
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- RWZYAGGXGHYGMB-UHFFFAOYSA-N o-aminobenzenecarboxylic acid Natural products NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 3
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 3
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- 125000000524 functional group Chemical group 0.000 claims description 2
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 108010088842 Fibrinolysin Proteins 0.000 description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
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- 230000007062 hydrolysis Effects 0.000 description 11
- 238000006460 hydrolysis reaction Methods 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
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- 230000000694 effects Effects 0.000 description 8
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- 208000007536 Thrombosis Diseases 0.000 description 7
- 230000020176 deacylation Effects 0.000 description 7
- 238000005947 deacylation reaction Methods 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 6
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000001788 irregular Effects 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 5
- 230000001588 bifunctional effect Effects 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
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- 238000002347 injection Methods 0.000 description 5
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- 239000002609 medium Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
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- 108010039627 Aprotinin Proteins 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000003024 amidolytic effect Effects 0.000 description 4
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical class N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 4
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- 238000006243 chemical reaction Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000004192 high performance gel permeation chromatography Methods 0.000 description 4
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 4
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- 238000003756 stirring Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
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- UJMDYLWCYJJYMO-UHFFFAOYSA-N benzene-1,2,3-tricarboxylic acid Chemical group OC(=O)C1=CC=CC(C(O)=O)=C1C(O)=O UJMDYLWCYJJYMO-UHFFFAOYSA-N 0.000 description 1
- DAOPOOMCXJPWPK-UHFFFAOYSA-N benzyl 4-aminobenzoate Chemical compound C1=CC(N)=CC=C1C(=O)OCC1=CC=CC=C1 DAOPOOMCXJPWPK-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000002528 coronary thrombosis Diseases 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000006240 deamidation Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 125000004119 disulfanediyl group Chemical group *SS* 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- YMQOKTHPONOAKK-UHFFFAOYSA-N hexyl 2-aminobenzoate Chemical compound CCCCCCOC(=O)C1=CC=CC=C1N YMQOKTHPONOAKK-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 102000046949 human MSC Human genes 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 125000005597 hydrazone group Chemical group 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
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- 238000009332 manuring Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 125000006366 methylene oxy carbonyl group Chemical group [H]C([H])([*:1])OC([*:2])=O 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229940085675 polyethylene glycol 800 Drugs 0.000 description 1
- 108010094020 polyglycine Proteins 0.000 description 1
- 229920000232 polyglycine polymer Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 108010082974 polysarcosine Proteins 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 238000010377 protein imaging Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
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- 239000010409 thin film Substances 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
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- 235000021419 vinegar Nutrition 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6435—Plasmin (3.4.21.7), i.e. fibrinolysin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6456—Plasminogen activators
- C12N9/6459—Plasminogen activators t-plasminogen activator (3.4.21.68), i.e. tPA
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21007—Plasmin (3.4.21.7), i.e. fibrinolysin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21069—Protein C activated (3.4.21.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8430253 | 1984-11-30 | ||
| GB848430253A GB8430253D0 (en) | 1984-11-30 | 1984-11-30 | Compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS61143325A true JPS61143325A (ja) | 1986-07-01 |
Family
ID=10570498
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60269207A Pending JPS61143325A (ja) | 1984-11-30 | 1985-11-29 | 新規化合物、その製法及びそれを含む医薬組成物 |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0184363A3 (OSRAM) |
| JP (1) | JPS61143325A (OSRAM) |
| AU (1) | AU5044685A (OSRAM) |
| DK (1) | DK552485A (OSRAM) |
| ES (3) | ES8704542A1 (OSRAM) |
| GB (1) | GB8430253D0 (OSRAM) |
| GR (1) | GR852876B (OSRAM) |
| PT (1) | PT81572B (OSRAM) |
| ZA (1) | ZA859159B (OSRAM) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019088270A1 (ja) * | 2017-11-02 | 2019-05-09 | 宇部興産株式会社 | 蛋白分解酵素の双頭型阻害剤 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL8503097A (nl) * | 1985-11-11 | 1987-06-01 | Leuven Res & Dev Vzw | Geneesmiddel met thrombolytische werking. |
| IE64284B1 (en) * | 1987-08-03 | 1995-07-26 | Ddi Pharmaceuticals | Conjugates of superoxide dismutase |
| CA1308377C (en) * | 1987-08-21 | 1992-10-06 | Henry Berger, Jr. | Complex of polyethyleneglycol and tissue plasminogen activator |
| US5272076A (en) * | 1991-06-13 | 1993-12-21 | Eli Lilly And Company | Compounds and methods for treatment of thromboembolic disorders using an adduct of t-PA |
| CA2440091C (en) * | 2001-03-23 | 2011-05-03 | Enzon, Inc. | Prodrugs of anticancer agents employing substituted aromatic acids |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0028489B1 (en) * | 1979-11-05 | 1983-10-05 | Beecham Group Plc | Enzyme derivatives, and their preparation |
| DE3361610D1 (en) * | 1982-04-07 | 1986-02-06 | Beecham Group Plc | Enzyme derivatives, process for preparing them and pharmaceutical compositions containing them |
| EP0109653A3 (en) * | 1982-11-17 | 1986-01-29 | Otsuka Pharmaceutical Co., Ltd. | Process for preparing urokinase complex |
| GB8334499D0 (en) * | 1983-12-24 | 1984-02-01 | Beecham Group Plc | Derivatives |
-
1984
- 1984-11-30 GB GB848430253A patent/GB8430253D0/en active Pending
-
1985
- 1985-11-25 EP EP85308534A patent/EP0184363A3/en not_active Withdrawn
- 1985-11-28 AU AU50446/85A patent/AU5044685A/en not_active Abandoned
- 1985-11-28 PT PT81572A patent/PT81572B/pt unknown
- 1985-11-28 DK DK552485A patent/DK552485A/da not_active Application Discontinuation
- 1985-11-29 GR GR852876A patent/GR852876B/el unknown
- 1985-11-29 JP JP60269207A patent/JPS61143325A/ja active Pending
- 1985-11-29 ZA ZA859159A patent/ZA859159B/xx unknown
- 1985-11-29 ES ES549459A patent/ES8704542A1/es not_active Expired
-
1986
- 1986-12-24 ES ES557266A patent/ES8708249A1/es not_active Expired
- 1986-12-24 ES ES557267A patent/ES8801616A1/es not_active Expired
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019088270A1 (ja) * | 2017-11-02 | 2019-05-09 | 宇部興産株式会社 | 蛋白分解酵素の双頭型阻害剤 |
| JPWO2019088270A1 (ja) * | 2017-11-02 | 2020-12-03 | 宇部興産株式会社 | 蛋白分解酵素の双頭型阻害剤 |
| US11465965B2 (en) | 2017-11-02 | 2022-10-11 | Ube Industries, Ltd. | Double-headed protease inhibitor |
Also Published As
| Publication number | Publication date |
|---|---|
| ES549459A0 (es) | 1987-04-01 |
| ES8704542A1 (es) | 1987-04-01 |
| GR852876B (OSRAM) | 1986-03-31 |
| DK552485A (da) | 1986-05-31 |
| ZA859159B (en) | 1986-11-26 |
| PT81572A (en) | 1985-12-01 |
| ES557266A0 (es) | 1987-10-01 |
| AU5044685A (en) | 1986-06-05 |
| ES8801616A1 (es) | 1988-02-16 |
| DK552485D0 (da) | 1985-11-28 |
| EP0184363A3 (en) | 1987-12-23 |
| PT81572B (en) | 1987-07-22 |
| ES8708249A1 (es) | 1987-10-01 |
| EP0184363A2 (en) | 1986-06-11 |
| ES557267A0 (es) | 1988-02-16 |
| GB8430253D0 (en) | 1985-01-09 |
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