NO314140B1 - Aminoguanidiner og alkoksyguanidiner som proteaseinhibitorer, deres fremstilling og anvendelse, farmasöytiske preparater og deres anvendelse,samt innretning - Google Patents
Aminoguanidiner og alkoksyguanidiner som proteaseinhibitorer, deres fremstilling og anvendelse, farmasöytiske preparater og deres anvendelse,samt innretning Download PDFInfo
- Publication number
- NO314140B1 NO314140B1 NO19992512A NO992512A NO314140B1 NO 314140 B1 NO314140 B1 NO 314140B1 NO 19992512 A NO19992512 A NO 19992512A NO 992512 A NO992512 A NO 992512A NO 314140 B1 NO314140 B1 NO 314140B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- methyl
- phenoxy
- propoxyguanidine
- phenylsulfonyloxy
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 31
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 20
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical class NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 title claims description 11
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 334
- 125000000217 alkyl group Chemical group 0.000 claims description 247
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 173
- -1 cyano, amino, hydroxyamino, phenyl Chemical group 0.000 claims description 170
- 229910052739 hydrogen Inorganic materials 0.000 claims description 122
- 239000001257 hydrogen Substances 0.000 claims description 119
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 111
- 239000011541 reaction mixture Substances 0.000 claims description 102
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 93
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 87
- 229910052757 nitrogen Inorganic materials 0.000 claims description 83
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 80
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 75
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 69
- 125000004076 pyridyl group Chemical group 0.000 claims description 66
- 125000003545 alkoxy group Chemical group 0.000 claims description 65
- JPGMSPJHRKUMDF-UHFFFAOYSA-N 2-propoxyguanidine Chemical compound CCCONC(N)=N JPGMSPJHRKUMDF-UHFFFAOYSA-N 0.000 claims description 61
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 60
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 60
- 239000002904 solvent Substances 0.000 claims description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 54
- 150000002431 hydrogen Chemical group 0.000 claims description 40
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 39
- 210000004369 blood Anatomy 0.000 claims description 34
- 239000008280 blood Substances 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 125000003386 piperidinyl group Chemical group 0.000 claims description 29
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 27
- 230000002401 inhibitory effect Effects 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 24
- 108090000190 Thrombin Proteins 0.000 claims description 23
- 230000015572 biosynthetic process Effects 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 22
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 229960004072 thrombin Drugs 0.000 claims description 21
- 239000003153 chemical reaction reagent Substances 0.000 claims description 20
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 19
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
- 125000001624 naphthyl group Chemical group 0.000 claims description 19
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000001544 thienyl group Chemical group 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 239000000460 chlorine Substances 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 241000124008 Mammalia Species 0.000 claims description 15
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 15
- 125000002757 morpholinyl group Chemical group 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000005518 carboxamido group Chemical group 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 14
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 13
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 12
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 12
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
- 208000007536 Thrombosis Diseases 0.000 claims description 10
- 125000001589 carboacyl group Chemical group 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- 239000003146 anticoagulant agent Substances 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 239000004305 biphenyl Substances 0.000 claims description 8
- 235000010290 biphenyl Nutrition 0.000 claims description 8
- 206010014561 Emphysema Diseases 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 230000017854 proteolysis Effects 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 229940127219 anticoagulant drug Drugs 0.000 claims description 6
- 230000017531 blood circulation Effects 0.000 claims description 6
- 208000037803 restenosis Diseases 0.000 claims description 6
- 238000003860 storage Methods 0.000 claims description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- 229940122388 Thrombin inhibitor Drugs 0.000 claims description 5
- 159000000021 acetate salts Chemical class 0.000 claims description 5
- 238000000502 dialysis Methods 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 5
- 239000003868 thrombin inhibitor Substances 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 4
- 108010049003 Fibrinogen Proteins 0.000 claims description 4
- 102000008946 Fibrinogen Human genes 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 206010033645 Pancreatitis Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 4
- HLMOWVJEQDTZRJ-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-methoxybenzenesulfonate Chemical compound COC1=CC=CC=C1S(=O)(=O)OC1=CC(C)=CC(OCCCONC(N)=N)=C1 HLMOWVJEQDTZRJ-UHFFFAOYSA-N 0.000 claims description 4
- 229940012952 fibrinogen Drugs 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- ZZNJGTBIIZXTIZ-UHFFFAOYSA-N 2-[carboxymethyl-[2-[3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenoxy]sulfonylphenyl]sulfonylamino]acetic acid Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N(CC(O)=O)CC(O)=O)=C1 ZZNJGTBIIZXTIZ-UHFFFAOYSA-N 0.000 claims description 3
- JBDALVUQSBGPGG-UHFFFAOYSA-N 3-[benzyl-[2-[3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenoxy]sulfonylphenyl]sulfonylamino]propanoic acid Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N(CCC(O)=O)CC=2C=CC=CC=2)=C1 JBDALVUQSBGPGG-UHFFFAOYSA-N 0.000 claims description 3
- GLMZSQWCNYGFEL-UHFFFAOYSA-N 4-[[2-[3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenoxy]sulfonylphenyl]sulfonyl-methylamino]benzoic acid Chemical compound C=1C=CC=C(S(=O)(=O)OC=2C=C(OCCCONC(N)=N)C=C(C)C=2)C=1S(=O)(=O)N(C)C1=CC=C(C(O)=O)C=C1 GLMZSQWCNYGFEL-UHFFFAOYSA-N 0.000 claims description 3
- 102100027612 Kallikrein-11 Human genes 0.000 claims description 3
- 101710152431 Trypsin-like protease Proteins 0.000 claims description 3
- GRMUCAFYWSZSCW-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-chlorobenzenesulfonate Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)Cl)=C1 GRMUCAFYWSZSCW-UHFFFAOYSA-N 0.000 claims description 3
- GMUCGSBSSVNWKT-UHFFFAOYSA-N [3-[[1-[(diaminomethylideneamino)oxymethyl]cyclopropyl]methoxy]-5-methylphenyl] 2-methylsulfonylbenzenesulfonate;hydrochloride Chemical compound Cl.C=1C(OS(=O)(=O)C=2C(=CC=CC=2)S(C)(=O)=O)=CC(C)=CC=1OCC1(CONC(N)=N)CC1 GMUCGSBSSVNWKT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- UCQFSGCWHRTMGG-UHFFFAOYSA-N pyrazole-1-carboximidamide Chemical class NC(=N)N1C=CC=N1 UCQFSGCWHRTMGG-UHFFFAOYSA-N 0.000 claims description 3
- UQJXXWHAJKRDKY-UHFFFAOYSA-N tert-butyl n-[[(2-methylpropan-2-yl)oxycarbonylamino]-methylsulfanylmethylidene]carbamate Chemical class CC(C)(C)OC(=O)NC(SC)=NC(=O)OC(C)(C)C UQJXXWHAJKRDKY-UHFFFAOYSA-N 0.000 claims description 3
- VVFJOYIOTKHSBM-UHFFFAOYSA-N 1-[2-[3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenoxy]sulfonylphenyl]sulfonylpiperidine-3-carboxylic acid Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N2CC(CCC2)C(O)=O)=C1 VVFJOYIOTKHSBM-UHFFFAOYSA-N 0.000 claims description 2
- DXQVYBWIXXGMDC-UHFFFAOYSA-N 1-[2-[3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenoxy]sulfonylphenyl]sulfonylpiperidine-4-carboxylic acid Chemical compound CC1=CC(OCCCON=C(N)N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N2CCC(CC2)C(O)=O)=C1 DXQVYBWIXXGMDC-UHFFFAOYSA-N 0.000 claims description 2
- FYNHGIUPLJWKJW-UHFFFAOYSA-N 2-[4-[2-[3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenoxy]sulfonylphenyl]sulfonylpiperazin-1-yl]acetic acid Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N2CCN(CC(O)=O)CC2)=C1 FYNHGIUPLJWKJW-UHFFFAOYSA-N 0.000 claims description 2
- MPVYXJHPOVYOQM-UHFFFAOYSA-N C=12OCOC2=CC=C(S(=O)(=O)OC=2C=C(OCCCONC(N)=N)C=C(C)C=2)C=1S(=O)(=O)N(CC)C1=CC=CC=C1 Chemical compound C=12OCOC2=CC=C(S(=O)(=O)OC=2C=C(OCCCONC(N)=N)C=C(C)C=2)C=1S(=O)(=O)N(CC)C1=CC=CC=C1 MPVYXJHPOVYOQM-UHFFFAOYSA-N 0.000 claims description 2
- CPUQBJNVLXQKKG-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-(4-piperidin-1-ylpiperidin-1-yl)sulfonylbenzenesulfonate Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N2CCC(CC2)N2CCCCC2)=C1 CPUQBJNVLXQKKG-UHFFFAOYSA-N 0.000 claims description 2
- FXLSWMTYFZQCNQ-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-(pyridin-4-ylmethylsulfamoyl)benzenesulfonate Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)NCC=2C=CN=CC=2)=C1 FXLSWMTYFZQCNQ-UHFFFAOYSA-N 0.000 claims description 2
- OAGRLPIBHULJBK-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-[2-cyanoethyl(furan-2-ylmethyl)sulfamoyl]benzenesulfonate Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N(CCC#N)CC=2OC=CC=2)=C1 OAGRLPIBHULJBK-UHFFFAOYSA-N 0.000 claims description 2
- JIZQPRHXKXENTN-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-[bis(2-cyanoethyl)sulfamoyl]benzenesulfonate Chemical compound CC1=CC(OCCCON=C(N)N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N(CCC#N)CCC#N)=C1 JIZQPRHXKXENTN-UHFFFAOYSA-N 0.000 claims description 2
- QJVPUZIELIAZSL-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-[methyl(2-pyridin-2-ylethyl)sulfamoyl]benzenesulfonate Chemical compound C=1C=CC=C(S(=O)(=O)OC=2C=C(OCCCONC(N)=N)C=C(C)C=2)C=1S(=O)(=O)N(C)CCC1=CC=CC=N1 QJVPUZIELIAZSL-UHFFFAOYSA-N 0.000 claims description 2
- BQAAZLYAVYJODE-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-[methyl(2-pyridin-4-ylethyl)sulfamoyl]benzenesulfonate Chemical compound C=1C=CC=C(S(=O)(=O)OC=2C=C(OCCCONC(N)=N)C=C(C)C=2)C=1S(=O)(=O)N(C)CCC1=CC=NC=C1 BQAAZLYAVYJODE-UHFFFAOYSA-N 0.000 claims description 2
- LOHDHCVDCOUGRH-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-[propyl(2-pyridin-2-ylethyl)sulfamoyl]benzenesulfonate Chemical compound C=1C=CC=C(S(=O)(=O)OC=2C=C(OCCCONC(N)=N)C=C(C)C=2)C=1S(=O)(=O)N(CCC)CCC1=CC=CC=N1 LOHDHCVDCOUGRH-UHFFFAOYSA-N 0.000 claims description 2
- QTDOSZWBVAHDOS-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 5-chloro-2-methoxybenzenesulfonate Chemical compound COC1=CC=C(Cl)C=C1S(=O)(=O)OC1=CC(C)=CC(OCCCONC(N)=N)=C1 QTDOSZWBVAHDOS-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 150000007857 hydrazones Chemical class 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 150000002823 nitrates Chemical class 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 claims 1
- DKSAKCGSOZZWKV-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-(2-morpholin-4-ylethylsulfamoyl)benzenesulfonate Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)NCCN2CCOCC2)=C1 DKSAKCGSOZZWKV-UHFFFAOYSA-N 0.000 claims 1
- JAVBCZCQKHIZRF-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-(4-ethylpiperazin-1-yl)sulfonylbenzenesulfonate Chemical compound C1CN(CC)CCN1S(=O)(=O)C1=CC=CC=C1S(=O)(=O)OC1=CC(C)=CC(OCCCONC(N)=N)=C1 JAVBCZCQKHIZRF-UHFFFAOYSA-N 0.000 claims 1
- MXAOJKILSVWVFM-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-(4-methylpiperazin-1-yl)sulfonylbenzenesulfonate Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=CC=C1S(=O)(=O)OC1=CC(C)=CC(OCCCONC(N)=N)=C1 MXAOJKILSVWVFM-UHFFFAOYSA-N 0.000 claims 1
- BXFZOBWEIDEZMP-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-(4-methylsulfonylpiperazin-1-yl)sulfonylbenzenesulfonate Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N2CCN(CC2)S(C)(=O)=O)=C1 BXFZOBWEIDEZMP-UHFFFAOYSA-N 0.000 claims 1
- FCKSEWCKWMTREY-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-(4-phenylpiperazin-1-yl)sulfonylbenzenesulfonate Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N2CCN(CC2)C=2C=CC=CC=2)=C1 FCKSEWCKWMTREY-UHFFFAOYSA-N 0.000 claims 1
- OVIOEDNCQOYHMI-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-(4-pyridin-2-ylpiperazin-1-yl)sulfonylbenzenesulfonate Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N2CCN(CC2)C=2N=CC=CC=2)=C1 OVIOEDNCQOYHMI-UHFFFAOYSA-N 0.000 claims 1
- VMQUPBFVQFHQAU-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-(4-pyrimidin-2-ylpiperazin-1-yl)sulfonylbenzenesulfonate Chemical compound CC1=CC(OCCCONC(N)=N)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)N2CCN(CC2)C=2N=CC=CN=2)=C1 VMQUPBFVQFHQAU-UHFFFAOYSA-N 0.000 claims 1
- WIVZBLIHXMFMRP-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-[4-(2-methoxyphenyl)piperazin-1-yl]sulfonylbenzenesulfonate Chemical compound COC1=CC=CC=C1N1CCN(S(=O)(=O)C=2C(=CC=CC=2)S(=O)(=O)OC=2C=C(OCCCONC(N)=N)C=C(C)C=2)CC1 WIVZBLIHXMFMRP-UHFFFAOYSA-N 0.000 claims 1
- DXZNRKMYFCBXDM-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-[benzyl-[2-(dimethylamino)ethyl]sulfamoyl]benzenesulfonate Chemical compound C=1C=CC=C(S(=O)(=O)OC=2C=C(OCCCON=C(N)N)C=C(C)C=2)C=1S(=O)(=O)N(CCN(C)C)CC1=CC=CC=C1 DXZNRKMYFCBXDM-UHFFFAOYSA-N 0.000 claims 1
- OZBQCTRYTMTTSK-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-[ethyl(pyridin-4-ylmethyl)sulfamoyl]benzenesulfonate Chemical compound C=1C=CC=C(S(=O)(=O)OC=2C=C(OCCCONC(N)=N)C=C(C)C=2)C=1S(=O)(=O)N(CC)CC1=CC=NC=C1 OZBQCTRYTMTTSK-UHFFFAOYSA-N 0.000 claims 1
- OQTRTYZUWQCRMS-UHFFFAOYSA-N [3-[3-(diaminomethylideneamino)oxypropoxy]-5-methylphenyl] 2-[methyl(pyridin-3-ylmethyl)sulfamoyl]benzenesulfonate Chemical compound C=1C=CC=C(S(=O)(=O)OC=2C=C(OCCCONC(N)=N)C=C(C)C=2)C=1S(=O)(=O)N(C)CC1=CC=CN=C1 OQTRTYZUWQCRMS-UHFFFAOYSA-N 0.000 claims 1
- ZQKDSAXXTBUEDK-UHFFFAOYSA-N [3-[[1-[carbamimidoyl(methoxy)amino]cyclopropyl]methoxy]-5-methylphenyl] 2-methylsulfonylbenzenesulfonate Chemical compound C=1C(C)=CC(OS(=O)(=O)C=2C(=CC=CC=2)S(C)(=O)=O)=CC=1OCC1(N(C(N)=N)OC)CC1 ZQKDSAXXTBUEDK-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/75—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing singly-bound oxygen atoms bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/76—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/77—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing carboxyl groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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AT (1) | ATE214693T1 (zh) |
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CN104857005B (zh) | 2010-12-31 | 2019-04-26 | 阿斯利康公司 | 精氨酸酶抑制剂及其使用方法 |
US9788539B2 (en) | 2011-05-17 | 2017-10-17 | Velico Medical, Inc. | Platelet protection solution having beta-galactosidase and sialidase inhibitors |
CA2835434A1 (en) | 2011-05-17 | 2012-11-22 | Velico Medical, Inc. | Improved platelet storage using a sialidase inhibitor |
CN102850451B (zh) * | 2011-06-29 | 2014-05-07 | 辽宁诺康生物制药有限责任公司 | 具有抑制纤溶酶活性的重组textilinin-1及其制备方法和应用 |
AU2013245729B2 (en) * | 2012-04-12 | 2016-09-29 | The Trustees Of The University Of Pennsylvania | Filovirus consensus antigens, nucleic acid constructs and vaccines made therefrom, and methods of using same |
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- 1997-11-26 HU HU0000733A patent/HUP0000733A3/hu unknown
- 1997-11-26 PL PL97333434A patent/PL333434A1/xx not_active Application Discontinuation
- 1997-11-26 WO PCT/US1997/021649 patent/WO1998023565A2/en not_active Application Discontinuation
- 1997-11-26 BR BR9713328-0A patent/BR9713328A/pt not_active Application Discontinuation
- 1997-11-26 EP EP97948537A patent/EP0944590B1/en not_active Expired - Lifetime
- 1997-11-26 NZ NZ336093A patent/NZ336093A/xx unknown
- 1997-11-26 KR KR1019997004642A patent/KR100587546B1/ko not_active IP Right Cessation
- 1997-11-26 DK DK97948537T patent/DK0944590T3/da active
- 1997-11-26 ES ES97948537T patent/ES2174309T3/es not_active Expired - Lifetime
- 1997-11-26 PT PT97948537T patent/PT944590E/pt unknown
- 1997-11-26 AU AU54584/98A patent/AU725058B2/en not_active Ceased
- 1997-11-26 AT AT97948537T patent/ATE214693T1/de not_active IP Right Cessation
- 1997-11-26 AR ARP970105565A patent/AR008327A1/es active IP Right Grant
- 1997-11-26 US US08/979,234 patent/US6235778B1/en not_active Expired - Lifetime
- 1997-11-26 IL IL13010297A patent/IL130102A/xx not_active IP Right Cessation
- 1997-11-26 EA EA199900544A patent/EA002740B1/ru not_active IP Right Cessation
- 1997-11-26 CA CA002273023A patent/CA2273023C/en not_active Expired - Fee Related
- 1997-11-26 CN CN97199940A patent/CN1237961A/zh active Pending
- 1997-11-26 JP JP52482998A patent/JP2001506606A/ja not_active Ceased
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1999
- 1999-05-25 NO NO19992512A patent/NO314140B1/no unknown
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2000
- 2000-11-28 US US09/722,363 patent/US6638931B1/en not_active Expired - Lifetime
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2001
- 2001-03-16 US US09/809,293 patent/US6518310B2/en not_active Expired - Lifetime
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2003
- 2003-02-06 US US10/359,078 patent/US6706765B2/en not_active Expired - Lifetime
- 2003-04-22 US US10/419,972 patent/US6730783B2/en not_active Expired - Lifetime
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