NO319101B1 - Nye benzotiofenforbindelser, fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende dem, samt anvendelse av forbindelsene - Google Patents
Nye benzotiofenforbindelser, fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende dem, samt anvendelse av forbindelsene Download PDFInfo
- Publication number
- NO319101B1 NO319101B1 NO19991957A NO991957A NO319101B1 NO 319101 B1 NO319101 B1 NO 319101B1 NO 19991957 A NO19991957 A NO 19991957A NO 991957 A NO991957 A NO 991957A NO 319101 B1 NO319101 B1 NO 319101B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compounds
- pyridinyl
- group
- benzo
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 150000001875 compounds Chemical class 0.000 title claims description 124
- 238000000034 method Methods 0.000 title claims description 43
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title abstract description 6
- -1 1-6C arylalkylene Chemical group 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 8
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 3
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 25
- 125000005605 benzo group Chemical group 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 11
- 208000007536 Thrombosis Diseases 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 230000007062 hydrolysis Effects 0.000 claims description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 6
- 230000007170 pathology Effects 0.000 claims description 5
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 5
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 150000003138 primary alcohols Chemical class 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- XYEAUXYPORAKOD-ZTKZIYFRSA-N (e)-3-[3-(4-hydroxyphenoxy)-5,6-bis(phenylmethoxy)-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid Chemical compound C=1C=NC=CC=1/C(C(=O)O)=C\C(=C(C1=CC=2OCC=3C=CC=CC=3)OC=3C=CC(O)=CC=3)SC1=CC=2OCC1=CC=CC=C1 XYEAUXYPORAKOD-ZTKZIYFRSA-N 0.000 claims description 2
- GGYUGABEHLLYJX-YRRMYEEHSA-N (e)-3-[5,6-bis(phenylmethoxy)-3-(4-phenylmethoxyphenoxy)-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid Chemical compound C=1C=NC=CC=1/C(C(=O)O)=C\C(=C(C1=CC=2OCC=3C=CC=CC=3)OC=3C=CC(OCC=4C=CC=CC=4)=CC=3)SC1=CC=2OCC1=CC=CC=C1 GGYUGABEHLLYJX-YRRMYEEHSA-N 0.000 claims description 2
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- SCOXUJLHNHFVDK-VUTHCHCSSA-N (e)-3-[3-(6-methylpyridin-3-yl)oxy-5,6-bis(phenylmethoxy)-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid Chemical compound C1=NC(C)=CC=C1OC(C1=CC(OCC=2C=CC=CC=2)=C(OCC=2C=CC=CC=2)C=C1S1)=C1\C=C(\C(O)=O)C1=CC=NC=C1 SCOXUJLHNHFVDK-VUTHCHCSSA-N 0.000 claims 1
- LTAHKZSKQPFEDZ-MWAVMZGNSA-N (e)-3-[6-methoxy-5-phenylmethoxy-3-(4-phenylmethoxyphenoxy)-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1OC=1C=2C=C(OCC=3C=CC=CC=3)C(OC)=CC=2SC=1\C=C(\C(O)=O)C1=CC=NC=C1 LTAHKZSKQPFEDZ-MWAVMZGNSA-N 0.000 claims 1
- 125000003172 aldehyde group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract 5
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 abstract 4
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 abstract 3
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 3
- 125000002252 acyl group Chemical group 0.000 abstract 2
- 125000003282 alkyl amino group Chemical group 0.000 abstract 2
- 229940054051 antipsychotic indole derivative Drugs 0.000 abstract 2
- 125000000732 arylene group Chemical group 0.000 abstract 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 2
- 125000002993 cycloalkylene group Chemical group 0.000 abstract 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 abstract 2
- 150000002475 indoles Chemical class 0.000 abstract 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000002431 aminoalkoxy group Chemical group 0.000 abstract 1
- 125000004663 dialkyl amino group Chemical group 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 abstract 1
- 239000000047 product Substances 0.000 description 29
- 238000004452 microanalysis Methods 0.000 description 26
- 239000003153 chemical reaction reagent Substances 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000758 substrate Substances 0.000 description 18
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 14
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000011734 sodium Substances 0.000 description 9
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- HXUKHSXNXWMNGH-UHFFFAOYSA-N 3-[3,4-bis(phenylmethoxy)phenyl]prop-2-enoic acid Chemical compound C=1C=CC=CC=1COC1=CC(C=CC(=O)O)=CC=C1OCC1=CC=CC=C1 HXUKHSXNXWMNGH-UHFFFAOYSA-N 0.000 description 6
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 238000001819 mass spectrum Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 235000011132 calcium sulphate Nutrition 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- FQCWLBGBAQCDJF-CSKARUKUSA-N (e)-3-(4-methoxy-3-phenylmethoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=C(\C=C\C(O)=O)C=C1OCC1=CC=CC=C1 FQCWLBGBAQCDJF-CSKARUKUSA-N 0.000 description 2
- SYUWBJQKJZVUFU-PXLXIMEGSA-N (e)-3-(6-methoxy-5-phenylmethoxy-3-pyridin-3-yloxy-1-benzothiophen-2-yl)-2-pyridin-4-ylprop-2-enoic acid Chemical compound C=1C=CN=CC=1OC=1C=2C=C(OCC=3C=CC=CC=3)C(OC)=CC=2SC=1\C=C(\C(O)=O)C1=CC=NC=C1 SYUWBJQKJZVUFU-PXLXIMEGSA-N 0.000 description 2
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 2
- DHLUJPLHLZJUBW-UHFFFAOYSA-N 6-methylpyridin-3-ol Chemical compound CC1=CC=C(O)C=N1 DHLUJPLHLZJUBW-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 108010001014 Plasminogen Activators Proteins 0.000 description 2
- 102000001938 Plasminogen Activators Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000001299 aldehydes Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- XFIIPDMBSAYALB-UHFFFAOYSA-N ethyl 2-[N-[[5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]methyl]anilino]acetate Chemical compound C=1C=CC=CC=1N(CC(=O)OCC)CC=1SC2=CC(OC)=C(OC)C=C2C=1OC1=CC=C(OC)C=C1 XFIIPDMBSAYALB-UHFFFAOYSA-N 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 229940127126 plasminogen activator Drugs 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- VJVZPTPOYCJFNI-UHFFFAOYSA-M (2-ethoxy-2-oxoethyl)-triphenylphosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC(=O)OCC)C1=CC=CC=C1 VJVZPTPOYCJFNI-UHFFFAOYSA-M 0.000 description 1
- PIVJVCRQCUYKNZ-HNNXBMFYSA-N (2s)-2-(benzylazaniumyl)-3-phenylpropanoate Chemical compound C([C@@H](C(=O)O)NCC=1C=CC=CC=1)C1=CC=CC=C1 PIVJVCRQCUYKNZ-HNNXBMFYSA-N 0.000 description 1
- YNOINBLMOVCCSL-UHFFFAOYSA-N (3-chloro-5,6-dimethoxy-1-benzothiophen-2-yl)methanol Chemical compound C1=C(OC)C(OC)=CC2=C1C(Cl)=C(CO)S2 YNOINBLMOVCCSL-UHFFFAOYSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- WSOBQOYHYGVEIR-CSKARUKUSA-N (e)-3-(3-methoxy-4-phenylmethoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1OCC1=CC=CC=C1 WSOBQOYHYGVEIR-CSKARUKUSA-N 0.000 description 1
- LRFSDLTWFHZEIV-LFIBNONCSA-N (e)-3-(5,6-dimethoxy-3-pyridin-3-yloxy-1-benzothiophen-2-yl)-2-pyridin-4-ylprop-2-enoic acid Chemical compound C=1C=CN=CC=1OC=1C=2C=C(OC)C(OC)=CC=2SC=1\C=C(\C(O)=O)C1=CC=NC=C1 LRFSDLTWFHZEIV-LFIBNONCSA-N 0.000 description 1
- HXUKHSXNXWMNGH-WYMLVPIESA-N (e)-3-[3,4-bis(phenylmethoxy)phenyl]prop-2-enoic acid Chemical compound C=1C=CC=CC=1COC1=CC(/C=C/C(=O)O)=CC=C1OCC1=CC=CC=C1 HXUKHSXNXWMNGH-WYMLVPIESA-N 0.000 description 1
- PSDFVFYAFUGJGF-RVDMUPIBSA-N (e)-3-[3-(2,4-difluorophenoxy)-5,6-dimethoxy-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid Chemical compound C=1C=C(F)C=C(F)C=1OC=1C=2C=C(OC)C(OC)=CC=2SC=1\C=C(\C(O)=O)C1=CC=NC=C1 PSDFVFYAFUGJGF-RVDMUPIBSA-N 0.000 description 1
- XWOTYKHTBLEFRS-MWAVMZGNSA-N (e)-3-[3-(4-methoxyphenoxy)-5,6-bis(phenylmethoxy)-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid Chemical compound C1=CC(OC)=CC=C1OC(C1=CC(OCC=2C=CC=CC=2)=C(OCC=2C=CC=CC=2)C=C1S1)=C1\C=C(\C(O)=O)C1=CC=NC=C1 XWOTYKHTBLEFRS-MWAVMZGNSA-N 0.000 description 1
- RBIJJSBVILGENA-DFKUXCBWSA-N (e)-3-[5,6-bis(phenylmethoxy)-3-quinolin-6-yloxy-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid Chemical compound C=1C=NC=CC=1/C(C(=O)O)=C\C(=C(C1=CC=2OCC=3C=CC=CC=3)OC=3C=C4C=CC=NC4=CC=3)SC1=CC=2OCC1=CC=CC=C1 RBIJJSBVILGENA-DFKUXCBWSA-N 0.000 description 1
- PSKZNNWDNOTXNI-QGOAFFKASA-N (e)-3-[5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid Chemical compound C1=CC(OC)=CC=C1OC(C1=CC(OC)=C(OC)C=C1S1)=C1\C=C(\C(O)=O)C1=CC=NC=C1 PSKZNNWDNOTXNI-QGOAFFKASA-N 0.000 description 1
- WHPXAWHTYGJEMT-CMDGGOBGSA-N (e)-3-[5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]prop-2-enoic acid Chemical compound C1=CC(OC)=CC=C1OC1=C(\C=C\C(O)=O)SC2=CC(OC)=C(OC)C=C12 WHPXAWHTYGJEMT-CMDGGOBGSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 1
- YSLDWASAMRAFFC-UHFFFAOYSA-N 2-[[5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]methylsulfamoyl]benzoic acid Chemical compound C1=CC(OC)=CC=C1OC(C1=CC(OC)=C(OC)C=C1S1)=C1CNS(=O)(=O)C1=CC=CC=C1C(O)=O YSLDWASAMRAFFC-UHFFFAOYSA-N 0.000 description 1
- HJBWJAPEBGSQPR-GQCTYLIASA-N 3,4-dimethoxycinnamic acid Chemical compound COC1=CC=C(\C=C\C(O)=O)C=C1OC HJBWJAPEBGSQPR-GQCTYLIASA-N 0.000 description 1
- HZPFNICVVDHZFB-UHFFFAOYSA-N 3-chloro-5,6-dimethoxy-1-benzothiophene-2-carbaldehyde Chemical compound C1=C(OC)C(OC)=CC2=C1C(Cl)=C(C=O)S2 HZPFNICVVDHZFB-UHFFFAOYSA-N 0.000 description 1
- FPOJTIOYSDDNKZ-UHFFFAOYSA-N 3-chloro-5,6-dimethoxy-1-benzothiophene-2-carbonyl chloride Chemical compound C1=C(OC)C(OC)=CC2=C1C(Cl)=C(C(Cl)=O)S2 FPOJTIOYSDDNKZ-UHFFFAOYSA-N 0.000 description 1
- SSWHNBXFRTZAOJ-UHFFFAOYSA-N 3-chloro-5,6-dimethoxy-1-benzothiophene-2-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC2=C1C(Cl)=C(C(O)=O)S2 SSWHNBXFRTZAOJ-UHFFFAOYSA-N 0.000 description 1
- CYKCUAPYWQDIKR-UHFFFAOYSA-N 4-(1h-imidazol-1-yl)phenol Chemical compound C1=CC(O)=CC=C1N1C=NC=C1 CYKCUAPYWQDIKR-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- JPVVRFKXDFIJLM-UHFFFAOYSA-N 4-pyridin-4-yloxyphenol Chemical compound C1=CC(O)=CC=C1OC1=CC=NC=C1 JPVVRFKXDFIJLM-UHFFFAOYSA-N 0.000 description 1
- DANMQSWQAGVFKV-UHFFFAOYSA-N 4-pyridin-4-ylphenol Chemical compound C1=CC(O)=CC=C1C1=CC=NC=C1 DANMQSWQAGVFKV-UHFFFAOYSA-N 0.000 description 1
- RCPTZZOSRHVFMJ-UHFFFAOYSA-N 5,6-bis(phenylmethoxy)-3-(4-pyridin-4-yloxyphenoxy)-1-benzothiophene-2-carbaldehyde Chemical compound C=1C=CC=CC=1COC=1C=C2C(OC=3C=CC(OC=4C=CN=CC=4)=CC=3)=C(C=O)SC2=CC=1OCC1=CC=CC=C1 RCPTZZOSRHVFMJ-UHFFFAOYSA-N 0.000 description 1
- WWPKRXOOVICNJY-UHFFFAOYSA-N 6-methoxynaphthalen-2-ol Chemical compound C1=C(O)C=CC2=CC(OC)=CC=C21 WWPKRXOOVICNJY-UHFFFAOYSA-N 0.000 description 1
- LKBKDKVMHWPZDB-UHFFFAOYSA-N 6-methoxypyridin-3-ol Chemical compound COC1=CC=C(O)C=N1 LKBKDKVMHWPZDB-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- FNJJJXWOKGCOAF-XQNSMLJCSA-N C1=CC2=CC(OC)=CC=C2C=C1OC(C1=CC(OC)=C(OC)C=C1S1)=C1\C=C(\C(O)=O)C1=CC=CC=C1 Chemical compound C1=CC2=CC(OC)=CC=C2C=C1OC(C1=CC(OC)=C(OC)C=C1S1)=C1\C=C(\C(O)=O)C1=CC=CC=C1 FNJJJXWOKGCOAF-XQNSMLJCSA-N 0.000 description 1
- PVOTYJVEUSGBDR-GZZLJNBRSA-N C=1C=NC=CC=1/C(C(=O)OCC)=C\C(=C(C1=CC=2OCC=3C=CC=CC=3)OC=3C=CC(OC(C)=O)=CC=3)SC1=CC=2OCC1=CC=CC=C1 Chemical compound C=1C=NC=CC=1/C(C(=O)OCC)=C\C(=C(C1=CC=2OCC=3C=CC=CC=3)OC=3C=CC(OC(C)=O)=CC=3)SC1=CC=2OCC1=CC=CC=C1 PVOTYJVEUSGBDR-GZZLJNBRSA-N 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- HJBWJAPEBGSQPR-UHFFFAOYSA-N DMCA Natural products COC1=CC=C(C=CC(O)=O)C=C1OC HJBWJAPEBGSQPR-UHFFFAOYSA-N 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- TWLLPUMZVVGILS-UHFFFAOYSA-N Ethyl 2-aminobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1N TWLLPUMZVVGILS-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000605403 Homo sapiens Plasminogen Proteins 0.000 description 1
- 101000609255 Homo sapiens Plasminogen activator inhibitor 1 Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102000017975 Protein C Human genes 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 102000029301 Protein S Human genes 0.000 description 1
- 108010066124 Protein S Proteins 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- SGQXEYIKJFPLDY-UHFFFAOYSA-N [5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]methanol Chemical compound C1=CC(OC)=CC=C1OC1=C(CO)SC2=CC(OC)=C(OC)C=C12 SGQXEYIKJFPLDY-UHFFFAOYSA-N 0.000 description 1
- SLMFSRDGXXBWDG-IPAQGAQISA-M [Na+].C1=CC(OC)=CC=C1OC(C1=CC(OCC=2C=CC=CC=2)=C(OCC=2C=CC=CC=2)C=C1S1)=C1\C=C(\C([O-])=O)C1=CC=NC=C1 Chemical compound [Na+].C1=CC(OC)=CC=C1OC(C1=CC(OCC=2C=CC=CC=2)=C(OCC=2C=CC=CC=2)C=C1S1)=C1\C=C(\C([O-])=O)C1=CC=NC=C1 SLMFSRDGXXBWDG-IPAQGAQISA-M 0.000 description 1
- RTRDLDVKFZLHDT-HRNDJLQDSA-M [Na+].C1=CC(OC)=CC=C1OC1=C(\C=C\C([O-])=O)SC2=CC(OC)=C(OC)C=C12 Chemical compound [Na+].C1=CC(OC)=CC=C1OC1=C(\C=C\C([O-])=O)SC2=CC(OC)=C(OC)C=C12 RTRDLDVKFZLHDT-HRNDJLQDSA-M 0.000 description 1
- QOZHSALPHMJVMM-XTWSRORZSA-M [Na+].C=1C=C(NC(C)=O)C=CC=1OC=1C=2C=C(OC)C(OC)=CC=2SC=1\C=C(\C([O-])=O)C1=CC=NC=C1 Chemical compound [Na+].C=1C=C(NC(C)=O)C=CC=1OC=1C=2C=C(OC)C(OC)=CC=2SC=1\C=C(\C([O-])=O)C1=CC=NC=C1 QOZHSALPHMJVMM-XTWSRORZSA-M 0.000 description 1
- GSXFALQIESHCES-HRKWZSCTSA-M [Na+].C=1C=C(OCC=2C=CC=CC=2)C=CC=1OC=1C=2C=C(OC)C(OC)=CC=2SC=1\C=C(\C([O-])=O)C1=CC=NC=C1 Chemical compound [Na+].C=1C=C(OCC=2C=CC=CC=2)C=CC=1OC=1C=2C=C(OC)C(OC)=CC=2SC=1\C=C(\C([O-])=O)C1=CC=NC=C1 GSXFALQIESHCES-HRKWZSCTSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000001175 calcium sulphate Substances 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- SIFFWUUOZSEHQC-ZHACJKMWSA-N ethyl (e)-3-[5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]prop-2-enoate Chemical compound CCOC(=O)\C=C\C=1SC2=CC(OC)=C(OC)C=C2C=1OC1=CC=C(OC)C=C1 SIFFWUUOZSEHQC-ZHACJKMWSA-N 0.000 description 1
- MLSGRWDEDYJNER-UHFFFAOYSA-N ethyl 2-anilinoacetate Chemical compound CCOC(=O)CNC1=CC=CC=C1 MLSGRWDEDYJNER-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 108010091897 factor V Leiden Proteins 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 102000043283 human SERPINE1 Human genes 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- HYGBPTWSPZXXTR-UHFFFAOYSA-N methyl 2-[[5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]methylsulfamoyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1S(=O)(=O)NCC1=C(OC=2C=CC(OC)=CC=2)C2=CC(OC)=C(OC)C=C2S1 HYGBPTWSPZXXTR-UHFFFAOYSA-N 0.000 description 1
- 208000001022 morbid obesity Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- OVYWMEWYEJLIER-UHFFFAOYSA-N quinolin-6-ol Chemical compound N1=CC=CC2=CC(O)=CC=C21 OVYWMEWYEJLIER-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- XKRKDWIHLGNALI-BOXHHOBZSA-M sodium (2S)-2-[[5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]methylamino]-3-phenylpropanoate Chemical compound [Na+].C1=CC(OC)=CC=C1OC(C1=CC(OC)=C(OC)C=C1S1)=C1CN[C@H](C([O-])=O)CC1=CC=CC=C1 XKRKDWIHLGNALI-BOXHHOBZSA-M 0.000 description 1
- KDVGQSOHIKNIIH-KRWCAOSLSA-M sodium (E)-3-[3-(2,4-difluorophenoxy)-5,6-dimethoxy-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoate Chemical compound [Na+].C=1C=C(F)C=C(F)C=1OC=1C=2C=C(OC)C(OC)=CC=2SC=1\C=C(\C([O-])=O)C1=CC=NC=C1 KDVGQSOHIKNIIH-KRWCAOSLSA-M 0.000 description 1
- KOSZUUCIGSHEKY-WXXHTBLMSA-M sodium (E)-3-[5,6-dimethoxy-3-(6-methoxynaphthalen-2-yl)oxy-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoate Chemical compound [Na+].C1=CC2=CC(OC)=CC=C2C=C1OC(C1=CC(OC)=C(OC)C=C1S1)=C1\C=C(\C([O-])=O)C1=CC=NC=C1 KOSZUUCIGSHEKY-WXXHTBLMSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- OQXUQQREELEAKG-UGAWPWHASA-M sodium;(e)-3-[5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]-2-phenylprop-2-enoate Chemical compound [Na+].C1=CC(OC)=CC=C1OC(C1=CC(OC)=C(OC)C=C1S1)=C1\C=C(\C([O-])=O)C1=CC=CC=C1 OQXUQQREELEAKG-UGAWPWHASA-M 0.000 description 1
- JGSIWPUSVBKLBU-PUBYZPQMSA-M sodium;(e)-3-[5,6-dimethoxy-3-(4-methoxyphenoxy)-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoate Chemical compound [Na+].C1=CC(OC)=CC=C1OC(C1=CC(OC)=C(OC)C=C1S1)=C1\C=C(\C([O-])=O)C1=CC=NC=C1 JGSIWPUSVBKLBU-PUBYZPQMSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/64—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9805239A FR2777886B1 (fr) | 1998-04-27 | 1998-04-27 | Nouveaux derives benzothiopheniques, benzofuraniques et indoliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO991957D0 NO991957D0 (no) | 1999-04-23 |
| NO991957L NO991957L (no) | 1999-10-28 |
| NO319101B1 true NO319101B1 (no) | 2005-06-20 |
Family
ID=9525701
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19991957A NO319101B1 (no) | 1998-04-27 | 1999-04-23 | Nye benzotiofenforbindelser, fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende dem, samt anvendelse av forbindelsene |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6048875A (xx) |
| EP (1) | EP0955299B1 (xx) |
| JP (1) | JP3957424B2 (xx) |
| CN (1) | CN1211362C (xx) |
| AT (1) | ATE214387T1 (xx) |
| AU (1) | AU744456B2 (xx) |
| BR (1) | BR9901298A (xx) |
| CA (1) | CA2270086C (xx) |
| DE (1) | DE69901006T2 (xx) |
| DK (1) | DK0955299T3 (xx) |
| ES (1) | ES2174579T3 (xx) |
| FR (1) | FR2777886B1 (xx) |
| HK (1) | HK1022694A1 (xx) |
| HU (1) | HUP9901403A1 (xx) |
| NO (1) | NO319101B1 (xx) |
| NZ (1) | NZ335388A (xx) |
| PT (1) | PT955299E (xx) |
| ZA (1) | ZA992941B (xx) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6162930A (en) * | 1998-03-06 | 2000-12-19 | Baylor University | Anti-mitotic agents which inhibit tubulin polymerization |
| FR2799756B1 (fr) * | 1999-10-15 | 2001-12-14 | Adir | Nouveaux derives benzothiopheniques, benzofuraniques et indoliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| EP1263763B1 (en) * | 2000-03-10 | 2007-07-25 | Baylor University | Tubulin binding ligands |
| US6699886B2 (en) * | 2001-05-31 | 2004-03-02 | Cellegy Pharmaceuticals, Inc. | Store operated calcium influx inhibitors and methods of use |
| ATE367812T1 (de) | 2001-06-20 | 2007-08-15 | Wyeth Corp | Substituierte indolsäurederivate als inhibitoren von plasminogen-aktivator-inhibitor-1 (pai-1) |
| TWI224101B (en) | 2001-06-20 | 2004-11-21 | Wyeth Corp | Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1) |
| UA80453C2 (en) | 2002-12-10 | 2007-09-25 | Derivatives of substituted dyhydropyranoindol-3,4-dion as inhibitors of plasminogen activator inhibitor-1 (pai-1) | |
| WO2004052855A2 (en) | 2002-12-10 | 2004-06-24 | Wyeth | Substituted 3-carbonyl-1h-indol-1-yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1) |
| CN1726191A (zh) | 2002-12-10 | 2006-01-25 | 惠氏公司 | 用作纤溶酶原激活物抑制剂－1(pai－1)的抑制剂的取代的吲哚氧代－乙酰氨基乙酸衍生物 |
| JP2006510673A (ja) * | 2002-12-10 | 2006-03-30 | ワイス | プラスミノゲンアクティベータインヒビター１（ｐａｉ−１）のインヒビターとしての、アリール、アリールオキシ、および、アルキルオキシ置換１ｈ−インドール−３−イルグリオキシル酸誘導体 |
| ES2268480T3 (es) | 2002-12-10 | 2007-03-16 | Wyeth | Derivados del acido 3-alquilo- y 3-arilalquilo-1h-indol-1-il-acetico sustituidos como inhibidores del inhibidor del activador del plasminogeno-1 (pai-1). |
| US7332521B2 (en) | 2003-09-25 | 2008-02-19 | Wyeth | Substituted indoles |
| US7163954B2 (en) | 2003-09-25 | 2007-01-16 | Wyeth | Substituted naphthyl benzothiophene acids |
| US7446201B2 (en) | 2003-09-25 | 2008-11-04 | Wyeth | Substituted heteroaryl benzofuran acids |
| US7265148B2 (en) * | 2003-09-25 | 2007-09-04 | Wyeth | Substituted pyrrole-indoles |
| US7342039B2 (en) | 2003-09-25 | 2008-03-11 | Wyeth | Substituted indole oximes |
| US7411083B2 (en) | 2003-09-25 | 2008-08-12 | Wyeth | Substituted acetic acid derivatives |
| US7420083B2 (en) | 2003-09-25 | 2008-09-02 | Wyeth | Substituted aryloximes |
| US7141592B2 (en) | 2003-09-25 | 2006-11-28 | Wyeth | Substituted oxadiazolidinediones |
| US7351726B2 (en) | 2003-09-25 | 2008-04-01 | Wyeth | Substituted oxadiazolidinediones |
| US7268159B2 (en) | 2003-09-25 | 2007-09-11 | Wyeth | Substituted indoles |
| US7442805B2 (en) | 2003-09-25 | 2008-10-28 | Wyeth | Substituted sulfonamide-indoles |
| US7582773B2 (en) | 2003-09-25 | 2009-09-01 | Wyeth | Substituted phenyl indoles |
| US7534894B2 (en) | 2003-09-25 | 2009-05-19 | Wyeth | Biphenyloxy-acids |
| KR20070055563A (ko) | 2004-08-23 | 2007-05-30 | 와이어쓰 | 혈전증 및 심혈관 질병의 치료에 유용한 플라스미노겐활성화제 억제제 타입-1(ｐａｉ-1)의 조절제로서의옥사졸로-나프틸 산 |
| RU2007106869A (ru) * | 2004-08-23 | 2008-09-27 | Вайет (Us) | Тиазол-нафтиловые кислоты как ингибиторы ингибитора активации плазминогена-1 |
| WO2006023864A1 (en) * | 2004-08-23 | 2006-03-02 | Wyeth | Pyrrolo-naphthyl acids as pai-1 inhibitors |
| BRPI0614340A2 (pt) * | 2005-08-17 | 2011-04-12 | Wyeth Corp | indóis substituìdos e métodos de seu uso |
| KR101475088B1 (ko) * | 2006-08-21 | 2014-12-23 | 제넨테크, 인크. | 아자-벤조티오페닐 화합물 및 사용 방법 |
| ATE531720T1 (de) * | 2006-08-21 | 2011-11-15 | Genentech Inc | Aza-benzofuranylverbindungen und anwendungsverfahren dafür |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4663344A (en) * | 1985-03-11 | 1987-05-05 | Merck & Co., Inc. | Anti-inflammatory and analgesic 3-hydroxybenzo[b]thiophene derivatives, compositions, and method of use therefor |
| IT1227362B (it) * | 1988-11-18 | 1991-04-08 | Istituto Biochimico Italiano | Derivati indolici, processo per la loro preparazione e loro uso comefarmaci antitrombotici |
| US5356926A (en) * | 1992-02-24 | 1994-10-18 | Warner-Lambert Company | 3-alkyloxy-, aryloxy-, or arylalkyloxy-benzo [β]thiophene-2-carboxamides as inhibitors of cell adhesion |
-
1998
- 1998-04-27 FR FR9805239A patent/FR2777886B1/fr not_active Expired - Fee Related
-
1999
- 1999-04-23 NO NO19991957A patent/NO319101B1/no unknown
- 1999-04-26 EP EP99401010A patent/EP0955299B1/fr not_active Expired - Lifetime
- 1999-04-26 NZ NZ335388A patent/NZ335388A/xx unknown
- 1999-04-26 CA CA002270086A patent/CA2270086C/fr not_active Expired - Fee Related
- 1999-04-26 ES ES99401010T patent/ES2174579T3/es not_active Expired - Lifetime
- 1999-04-26 PT PT99401010T patent/PT955299E/pt unknown
- 1999-04-26 US US09/299,271 patent/US6048875A/en not_active Expired - Fee Related
- 1999-04-26 DE DE69901006T patent/DE69901006T2/de not_active Expired - Fee Related
- 1999-04-26 JP JP11736799A patent/JP3957424B2/ja not_active Expired - Fee Related
- 1999-04-26 DK DK99401010T patent/DK0955299T3/da active
- 1999-04-26 ZA ZA9902941A patent/ZA992941B/xx unknown
- 1999-04-26 AT AT99401010T patent/ATE214387T1/de not_active IP Right Cessation
- 1999-04-27 HU HU9901403A patent/HUP9901403A1/hu unknown
- 1999-04-27 AU AU24021/99A patent/AU744456B2/en not_active Ceased
- 1999-04-27 CN CNB991051815A patent/CN1211362C/zh not_active Expired - Fee Related
- 1999-04-27 BR BR9901298-7A patent/BR9901298A/pt not_active Application Discontinuation
-
2000
- 2000-03-21 HK HK00101709A patent/HK1022694A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CN1235156A (zh) | 1999-11-17 |
| CA2270086C (fr) | 2005-04-05 |
| DE69901006T2 (de) | 2002-11-07 |
| AU2402199A (en) | 1999-11-04 |
| NO991957D0 (no) | 1999-04-23 |
| ES2174579T3 (es) | 2002-11-01 |
| AU744456B2 (en) | 2002-02-21 |
| JP3957424B2 (ja) | 2007-08-15 |
| HU9901403D0 (en) | 1999-06-28 |
| FR2777886B1 (fr) | 2002-05-31 |
| NZ335388A (en) | 2000-03-27 |
| ZA992941B (en) | 1999-10-26 |
| US6048875A (en) | 2000-04-11 |
| BR9901298A (pt) | 2000-05-02 |
| CA2270086A1 (fr) | 1999-10-27 |
| ATE214387T1 (de) | 2002-03-15 |
| NO991957L (no) | 1999-10-28 |
| CN1211362C (zh) | 2005-07-20 |
| FR2777886A1 (fr) | 1999-10-29 |
| PT955299E (pt) | 2002-07-31 |
| EP0955299B1 (fr) | 2002-03-13 |
| HUP9901403A1 (hu) | 2000-06-28 |
| DK0955299T3 (da) | 2002-06-24 |
| EP0955299A1 (fr) | 1999-11-10 |
| DE69901006D1 (de) | 2002-04-18 |
| JPH11349586A (ja) | 1999-12-21 |
| HK1022694A1 (en) | 2000-08-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO319101B1 (no) | Nye benzotiofenforbindelser, fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende dem, samt anvendelse av forbindelsene | |
| US6302837B1 (en) | Benzothiophene, benzofuran and indole compounds | |
| CA2455863C (en) | Tetrahydroquinoline derivatives as gamma secretase inhibitors | |
| KR100240536B1 (ko) | 세포간질 메탈로프로티에이즈 억제제 | |
| US5929097A (en) | Preparation and use of ortho-sulfonamido aryl hydroxamic acids as matrix metalloproteinase and tace inhibitors | |
| JP5073149B2 (ja) | アシル化インダニルアミンおよび医薬としてのその使用 | |
| JP2951527B2 (ja) | アリールスルホンアミド置換化ヒドロキサム酸 | |
| US6855722B2 (en) | Substituted indoles and their use as integrin antagonists | |
| US20050043304A1 (en) | Novel amine derivative having human beta-tryptase inhibitory activity and drugs containing the same | |
| US6825352B2 (en) | Preparation and use of ortho-sulfonamido arylhydroxamic acids as matrix metalloproteinase inhibitors | |
| JPH09110866A (ja) | 複素環式アリール−、アルキル−およびシクロアルキルアセトアミド類 | |
| NO178496B (no) | Kinolin-2-yl-metoksybenzylhydroksyurea | |
| Sato et al. | Synthesis and evaluation of novel fluorinated sulotroban-related sulfonamide derivatives as thromboxane A2 receptor antagonists | |
| US6417203B1 (en) | Antithrombotic agents | |
| MXPA99011901A (en) | New amidino derivatives and their use as thrombin inhibitors |