NO328523B1 - Faktor VIIa-inhibitorer, fremgangsmate for fremstilling av slike og farmasoytisk preparat omfattende slike, samt anvendelse av inhibitorene for fremstilling av farmasoytisk preparat. - Google Patents

Faktor VIIa-inhibitorer, fremgangsmate for fremstilling av slike og farmasoytisk preparat omfattende slike, samt anvendelse av inhibitorene for fremstilling av farmasoytisk preparat. Download PDF

Info

Publication number: NO328523B1
Authority: NO; Norway
Prior art keywords: paph; alloc; glu; compound; cha
Prior art date: 1998-09-15

Application number

NO20011293A

Other languages

English (en)

Norwegian (no)

Other versions

NO20011293D0 (no

NO20011293L (no

Inventor

Pavel Safar

Peter Wildgoose

Alena Safarova

Original Assignee

Sanofi Aventis Deutschland

Priority date (The priority date 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 date listed.)

1998-09-15

Filing date

2001-03-14

Publication date

2010-03-08

2001-03-14 Application filed by Sanofi Aventis Deutschland filed Critical Sanofi Aventis Deutschland

2001-03-14 Publication of NO20011293D0 publication Critical patent/NO20011293D0/no

2001-05-04 Publication of NO20011293L publication Critical patent/NO20011293L/no

2010-03-08 Publication of NO328523B1 publication Critical patent/NO328523B1/no

Links

238000000034 method Methods 0.000 title claims description 52
238000002360 preparation method Methods 0.000 title claims description 26
230000008569 process Effects 0.000 title claims description 13
239000000825 pharmaceutical preparation Substances 0.000 title claims description 9
239000003112 inhibitor Substances 0.000 title description 9
229940082863 Factor VIIa inhibitor Drugs 0.000 title 1
239000008194 pharmaceutical composition Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 163
-1 Leu Chemical compound 0.000 claims description 84
239000011347 resin Substances 0.000 claims description 77
229920005989 resin Polymers 0.000 claims description 77
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 35
125000003277 amino group Chemical group 0.000 claims description 31
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 30
230000008878 coupling Effects 0.000 claims description 28
238000010168 coupling process Methods 0.000 claims description 28
238000005859 coupling reaction Methods 0.000 claims description 28
239000000203 mixture Substances 0.000 claims description 25
230000002401 inhibitory effect Effects 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 18
230000023555 blood coagulation Effects 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
125000001424 substituent group Chemical group 0.000 claims description 16
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 13
JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 10
150000002148 esters Chemical class 0.000 claims description 10
125000006239 protecting group Chemical group 0.000 claims description 10
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
239000003937 drug carrier Substances 0.000 claims description 9
238000003776 cleavage reaction Methods 0.000 claims description 8
230000007017 scission Effects 0.000 claims description 8
239000000126 substance Substances 0.000 claims description 7
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 6
150000001408 amides Chemical class 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
238000010511 deprotection reaction Methods 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
208000037803 restenosis Diseases 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 claims description 4
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 4
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000004344 phenylpropyl group Chemical group 0.000 claims description 4
XPRCPVGCTGELMN-QMMMGPOBSA-N (2s)-2-amino-3-(4-carbamimidoylphenyl)propanoic acid Chemical group OC(=O)[C@@H](N)CC1=CC=C(C(N)=N)C=C1 XPRCPVGCTGELMN-QMMMGPOBSA-N 0.000 claims description 3
ONOURAAVVKGJNM-SCZZXKLOSA-N (2s,3r)-2-azaniumyl-3-phenylmethoxybutanoate Chemical compound [O-]C(=O)[C@@H]([NH3+])[C@@H](C)OCC1=CC=CC=C1 ONOURAAVVKGJNM-SCZZXKLOSA-N 0.000 claims description 3
101100240527 Caenorhabditis elegans nhr-22 gene Proteins 0.000 claims description 3
OGNKZWAQLJPNLL-STQMWFEESA-N Phe(4-NO2)-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)C)CC1=CC=C([N+]([O-])=O)C=C1 OGNKZWAQLJPNLL-STQMWFEESA-N 0.000 claims description 3
208000001435 Thromboembolism Diseases 0.000 claims description 3
235000019445 benzyl alcohol Nutrition 0.000 claims description 3
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
238000010561 standard procedure Methods 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
230000028709 inflammatory response Effects 0.000 claims description 2
239000008177 pharmaceutical agent Substances 0.000 claims description 2
230000002792 vascular Effects 0.000 claims description 2
108090000765 processed proteins & peptides Proteins 0.000 description 66
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
150000001413 amino acids Chemical class 0.000 description 46
235000001014 amino acid Nutrition 0.000 description 45
229940024606 amino acid Drugs 0.000 description 45
230000015572 biosynthetic process Effects 0.000 description 40
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
230000000694 effects Effects 0.000 description 34
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 31
238000003786 synthesis reaction Methods 0.000 description 30
238000004949 mass spectrometry Methods 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
238000004128 high performance liquid chromatography Methods 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
238000006467 substitution reaction Methods 0.000 description 19
125000004432 carbon atom Chemical group C* 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
OTKXCALUHMPIGM-FQEVSTJZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 OTKXCALUHMPIGM-FQEVSTJZSA-N 0.000 description 15
125000005647 linker group Chemical group 0.000 description 15
HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 15
108090000190 Thrombin Proteins 0.000 description 14
125000001841 imino group Chemical group [H]N=* 0.000 description 14
230000004048 modification Effects 0.000 description 14
238000012986 modification Methods 0.000 description 14
229960004072 thrombin Drugs 0.000 description 14
230000015271 coagulation Effects 0.000 description 13
238000005345 coagulation Methods 0.000 description 13
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
108010074860 Factor Xa Proteins 0.000 description 11
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 11
125000000217 alkyl group Chemical group 0.000 description 11
HIJAUEZBPWTKIV-QFIPXVFZSA-N (2s)-3-cyclohexyl-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C1CCCCC1 HIJAUEZBPWTKIV-QFIPXVFZSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
108010000499 Thromboplastin Proteins 0.000 description 10
102000002262 Thromboplastin Human genes 0.000 description 10
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
230000005764 inhibitory process Effects 0.000 description 9
102000004196 processed proteins & peptides Human genes 0.000 description 9
239000000047 product Substances 0.000 description 9
238000011282 treatment Methods 0.000 description 9
208000032843 Hemorrhage Diseases 0.000 description 8
125000003118 aryl group Chemical group 0.000 description 8
208000034158 bleeding Diseases 0.000 description 8
230000000740 bleeding effect Effects 0.000 description 8
239000003814 drug Substances 0.000 description 8
229960002897 heparin Drugs 0.000 description 8
229920000669 heparin Polymers 0.000 description 8
239000002904 solvent Substances 0.000 description 8
125000002252 acyl group Chemical group 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
239000007787 solid Substances 0.000 description 7
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
108091005804 Peptidases Proteins 0.000 description 6
102000035195 Peptidases Human genes 0.000 description 6
208000007536 Thrombosis Diseases 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
239000003146 anticoagulant agent Substances 0.000 description 6
229940079593 drug Drugs 0.000 description 6
239000000463 material Substances 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
239000004365 Protease Substances 0.000 description 5
206010047249 Venous thrombosis Diseases 0.000 description 5
229940127219 anticoagulant drug Drugs 0.000 description 5
238000003556 assay Methods 0.000 description 5
210000004899 c-terminal region Anatomy 0.000 description 5
125000006165 cyclic alkyl group Chemical group 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
201000010099 disease Diseases 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
235000018102 proteins Nutrition 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
108090000623 proteins and genes Proteins 0.000 description 5
QTWZCODKTSUZJN-LJAQVGFWSA-N (2s)-5-[[amino-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]methylidene]amino]-2-(9h-fluoren-9-ylmethoxycarbonylamino)pentanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)N[C@H](C(O)=O)CCCN=C(N)NS(=O)(=O)C(C(C)=C1C)=C(C)C2=C1OC(C)(C)CC2 QTWZCODKTSUZJN-LJAQVGFWSA-N 0.000 description 4
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
239000005695 Ammonium acetate Substances 0.000 description 4
150000008574 D-amino acids Chemical class 0.000 description 4
206010051055 Deep vein thrombosis Diseases 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
108010054265 Factor VIIa Proteins 0.000 description 4
FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 4
235000019257 ammonium acetate Nutrition 0.000 description 4
229940043376 ammonium acetate Drugs 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
239000008280 blood Substances 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 4
239000003480 eluent Substances 0.000 description 4
229940088598 enzyme Drugs 0.000 description 4
229940012414 factor viia Drugs 0.000 description 4
230000020764 fibrinolysis Effects 0.000 description 4
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
239000010931 gold Substances 0.000 description 4
229910052737 gold Inorganic materials 0.000 description 4
230000037361 pathway Effects 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
239000000523 sample Substances 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
238000012546 transfer Methods 0.000 description 4
238000005406 washing Methods 0.000 description 4
VUCNQOPCYRJCGQ-UHFFFAOYSA-N 2-[4-(hydroxymethyl)phenoxy]acetic acid Chemical compound OCC1=CC=C(OCC(O)=O)C=C1 VUCNQOPCYRJCGQ-UHFFFAOYSA-N 0.000 description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
108010061932 Factor VIIIa Proteins 0.000 description 3
102000009123 Fibrin Human genes 0.000 description 3
108010073385 Fibrin Proteins 0.000 description 3
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 3
239000007821 HATU Substances 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
230000004913 activation Effects 0.000 description 3
150000001409 amidines Chemical class 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
229910052786 argon Inorganic materials 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
125000002843 carboxylic acid group Chemical group 0.000 description 3
238000004587 chromatography analysis Methods 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
239000000839 emulsion Substances 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
229950003499 fibrin Drugs 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
125000000592 heterocycloalkyl group Chemical group 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
239000003055 low molecular weight heparin Substances 0.000 description 3
229940127215 low-molecular weight heparin Drugs 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 3
230000003278 mimic effect Effects 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
238000010647 peptide synthesis reaction Methods 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
239000002994 raw material Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
229910052717 sulfur Inorganic materials 0.000 description 3
239000003826 tablet Substances 0.000 description 3
ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 3
LIWKOFAHRLBNMG-FQEVSTJZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCNC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 LIWKOFAHRLBNMG-FQEVSTJZSA-N 0.000 description 2
FJSOTHAUCCEZLI-KRWDZBQOSA-N (2s)-3-cyano-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CC#N)C(=O)O)C3=CC=CC=C3C2=C1 FJSOTHAUCCEZLI-KRWDZBQOSA-N 0.000 description 2
MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
108010049003 Fibrinogen Proteins 0.000 description 2
102000008946 Fibrinogen Human genes 0.000 description 2
108010088842 Fibrinolysin Proteins 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
150000008575 L-amino acids Chemical class 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
241000282520 Papio Species 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
239000000654 additive Substances 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
125000003368 amide group Chemical group 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
150000003862 amino acid derivatives Chemical class 0.000 description 2
238000002399 angioplasty Methods 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
230000010100 anticoagulation Effects 0.000 description 2
230000008901 benefit Effects 0.000 description 2
239000003130 blood coagulation factor inhibitor Substances 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
239000000872 buffer Substances 0.000 description 2
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
125000003636 chemical group Chemical group 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 2
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
229940012952 fibrinogen Drugs 0.000 description 2
150000004676 glycans Chemical class 0.000 description 2
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
125000004404 heteroalkyl group Chemical group 0.000 description 2
125000001072 heteroaryl group Chemical group 0.000 description 2
125000004446 heteroarylalkyl group Chemical group 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000006623 intrinsic pathway Effects 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000007791 liquid phase Substances 0.000 description 2
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
229940012957 plasmin Drugs 0.000 description 2
229920001282 polysaccharide Polymers 0.000 description 2
239000005017 polysaccharide Substances 0.000 description 2
108010014806 prothrombinase complex Proteins 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000004007 reversed phase HPLC Methods 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000008259 solid foam Substances 0.000 description 2
239000007790 solid phase Substances 0.000 description 2
238000010532 solid phase synthesis reaction Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
230000000451 tissue damage Effects 0.000 description 2
231100000827 tissue damage Toxicity 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
125000004417 unsaturated alkyl group Chemical group 0.000 description 2
239000000052 vinegar Substances 0.000 description 2
235000021419 vinegar Nutrition 0.000 description 2
XHTORJWGZKCDGL-GRGSLBFTSA-N (2s)-1-[(2r,3r)-2-amino-3-methylpentanoyl]-n-[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide Chemical compound CC[C@@H](C)[C@@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC1=CC=C([N+]([O-])=O)C=C1 XHTORJWGZKCDGL-GRGSLBFTSA-N 0.000 description 1
MPVGCCAXXFLGIU-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-(prop-2-enoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CNC(=O)OCC=C)C(=O)O)C3=CC=CC=C3C2=C1 MPVGCCAXXFLGIU-IBGZPJMESA-N 0.000 description 1
KSDTXRUIZMTBNV-INIZCTEOSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)butanedioic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CC(=O)O)C(O)=O)C3=CC=CC=C3C2=C1 KSDTXRUIZMTBNV-INIZCTEOSA-N 0.000 description 1
KWIPUXXIFQQMKN-VIFPVBQESA-N (2s)-2-amino-3-(4-cyanophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(C#N)C=C1 KWIPUXXIFQQMKN-VIFPVBQESA-N 0.000 description 1
OZBTURSCNGTHKT-FVGYRXGTSA-N (2s)-2-amino-n-[(3-chlorophenyl)methyl]butanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=O)C[C@H](N)C(=O)NCC1=CC=CC(Cl)=C1 OZBTURSCNGTHKT-FVGYRXGTSA-N 0.000 description 1
BWQQGHPODCJZDB-NRFANRHFSA-N (2s)-2-cyclohexyl-2-(9h-fluoren-9-ylmethoxycarbonylamino)acetic acid Chemical compound C1([C@H](NC(=O)OCC2C3=CC=CC=C3C3=CC=CC=C32)C(=O)O)CCCCC1 BWQQGHPODCJZDB-NRFANRHFSA-N 0.000 description 1
YUGBZNJSGOBFOV-INIZCTEOSA-N (2s)-4-amino-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-oxobutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CC(=O)N)C(O)=O)C3=CC=CC=C3C2=C1 YUGBZNJSGOBFOV-INIZCTEOSA-N 0.000 description 1
CTXPLTPDOISPTE-YPMHNXCESA-N (2s,3r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylmethoxybutanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)[C@@H](C)OCC1=CC=CC=C1 CTXPLTPDOISPTE-YPMHNXCESA-N 0.000 description 1
125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 description 1
NDKDFTQNXLHCGO-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)acetic acid Chemical compound C1=CC=C2C(COC(=O)NCC(=O)O)C3=CC=CC=C3C2=C1 NDKDFTQNXLHCGO-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
125000004924 2-naphthylethyl group Chemical group C1=C(C=CC2=CC=CC=C12)CC* 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
KISZTEOELCMZPY-UHFFFAOYSA-N 3,3-diphenylpropylamine Chemical compound C=1C=CC=CC=1C(CCN)C1=CC=CC=C1 KISZTEOELCMZPY-UHFFFAOYSA-N 0.000 description 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000002373 5 membered heterocyclic group Chemical class 0.000 description 1
VZHNAVSRNGLHRD-UHFFFAOYSA-N 5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoic acid Chemical compound CC(C)(C)OC(=O)CCCC(O)=O VZHNAVSRNGLHRD-UHFFFAOYSA-N 0.000 description 1
YIFPACFSZQWAQF-FJXQXJEOSA-N 5-o-tert-butyl 1-o-methyl (2s)-2-aminopentanedioate;hydron;chloride Chemical compound Cl.COC(=O)[C@@H](N)CCC(=O)OC(C)(C)C YIFPACFSZQWAQF-FJXQXJEOSA-N 0.000 description 1
125000004070 6 membered heterocyclic group Chemical class 0.000 description 1
LRAMQBKQEYONOM-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(3-aminopropyl)carbamate Chemical compound C1=CC=C2C(COC(=O)NCCCN)C3=CC=CC=C3C2=C1 LRAMQBKQEYONOM-UHFFFAOYSA-N 0.000 description 1
206010001052 Acute respiratory distress syndrome Diseases 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
206010002388 Angina unstable Diseases 0.000 description 1
102000004411 Antithrombin III Human genes 0.000 description 1
108090000935 Antithrombin III Proteins 0.000 description 1
206010003162 Arterial injury Diseases 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
102000015081 Blood Coagulation Factors Human genes 0.000 description 1
108010039209 Blood Coagulation Factors Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241001146702 Candidatus Entotheonella factor Species 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
102100023804 Coagulation factor VII Human genes 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 description 1
CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 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
229940123900 Direct thrombin inhibitor Drugs 0.000 description 1
108010062466 Enzyme Precursors Proteins 0.000 description 1
102000010911 Enzyme Precursors Human genes 0.000 description 1
102000018389 Exopeptidases Human genes 0.000 description 1
108010091443 Exopeptidases Proteins 0.000 description 1
108010023321 Factor VII Proteins 0.000 description 1
108010074105 Factor Va Proteins 0.000 description 1
108010014173 Factor X Proteins 0.000 description 1
229940123583 Factor Xa inhibitor Drugs 0.000 description 1
229920002971 Heparan sulfate Polymers 0.000 description 1
241001622557 Hesperia Species 0.000 description 1
108010007267 Hirudins Proteins 0.000 description 1
102000007625 Hirudins Human genes 0.000 description 1
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 1
206010061216 Infarction Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 description 1
208000034486 Multi-organ failure Diseases 0.000 description 1
208000010718 Multiple Organ Failure Diseases 0.000 description 1
XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 1
108010049175 N-substituted Glycines Proteins 0.000 description 1
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
108010094028 Prothrombin Proteins 0.000 description 1
102100027378 Prothrombin Human genes 0.000 description 1
208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
206010040047 Sepsis Diseases 0.000 description 1
108010022999 Serine Proteases Proteins 0.000 description 1
102000012479 Serine Proteases Human genes 0.000 description 1
208000006011 Stroke Diseases 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
102100030951 Tissue factor pathway inhibitor Human genes 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
241000251539 Vertebrata <Metazoa> Species 0.000 description 1
DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
231100000230 acceptable toxicity Toxicity 0.000 description 1
229960001138 acetylsalicylic acid Drugs 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
150000001265 acyl fluorides Chemical class 0.000 description 1
208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
HXBPYFMVGFDZFT-UHFFFAOYSA-N allyl isocyanate Chemical compound C=CCN=C=O HXBPYFMVGFDZFT-UHFFFAOYSA-N 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000003277 amino acid sequence analysis Methods 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
230000002785 anti-thrombosis Effects 0.000 description 1
229960005348 antithrombin iii Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
150000001509 aspartic acid derivatives Chemical class 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
239000011324 bead Substances 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
AGSPXMVUFBBBMO-UHFFFAOYSA-N beta-aminopropionitrile Chemical compound NCCC#N AGSPXMVUFBBBMO-UHFFFAOYSA-N 0.000 description 1
OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
108010055460 bivalirudin Proteins 0.000 description 1
229960001500 bivalirudin Drugs 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
239000003114 blood coagulation factor Substances 0.000 description 1
229940019700 blood coagulation factors Drugs 0.000 description 1
239000012267 brine Substances 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
230000004087 circulation Effects 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
230000035602 clotting Effects 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
238000010276 construction Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000007887 coronary angioplasty Methods 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
239000013058 crude material Substances 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000006638 cyclopentyl carbonyl group Chemical group 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
230000006624 extrinsic pathway Effects 0.000 description 1
229940012413 factor vii Drugs 0.000 description 1
239000003925 fat Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000036541 health Effects 0.000 description 1
230000023597 hemostasis Effects 0.000 description 1
229940006607 hirudin Drugs 0.000 description 1
WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000007574 infarction Effects 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000003978 infusion fluid Substances 0.000 description 1
108091006086 inhibitor proteins Proteins 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
108010075079 isoleucyl-prolyl-arginine-4-nitroanilide Proteins 0.000 description 1
125000006229 isopropoxyethyl group Chemical group [H]C([H])([H])C([H])(OC([H])([H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
238000003367 kinetic assay Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000012423 maintenance Methods 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
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
229920005990 polystyrene resin Polymers 0.000 description 1
239000004810 polytetrafluoroethylene Substances 0.000 description 1
229920001343 polytetrafluoroethylene Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
229940039716 prothrombin Drugs 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical group O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000006965 reversible inhibition Effects 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
239000003001 serine protease inhibitor Substances 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
235000011044 succinic acid Nutrition 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000011477 surgical intervention Methods 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000000725 suspension Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical class CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
239000003868 thrombin inhibitor Substances 0.000 description 1
230000001732 thrombotic effect Effects 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
238000011541 total hip replacement Methods 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000000825 ultraviolet detection Methods 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000001993 wax Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
230000029663 wound healing Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1019—Tetrapeptides with the first amino acid being basic
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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]
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T436/105831—Protein or peptide standard or control [e.g., hemoglobin, etc.]

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
Hematology (AREA)
Vascular Medicine (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

NO20011293A 1998-09-15 2001-03-14 Faktor VIIa-inhibitorer, fremgangsmate for fremstilling av slike og farmasoytisk preparat omfattende slike, samt anvendelse av inhibitorene for fremstilling av farmasoytisk preparat. NO328523B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP98117506A EP0987274A1 (en)	1998-09-15	1998-09-15	Factor VIIa Inhibitors
PCT/EP1999/006449 WO2000015658A1 (en)	1998-09-15	1999-09-02	FACTOR VIIa INHIBITORS

Publications (3)

Publication Number	Publication Date
NO20011293D0 NO20011293D0 (no)	2001-03-14
NO20011293L NO20011293L (no)	2001-05-04
NO328523B1 true NO328523B1 (no)	2010-03-08

Family

ID=8232644

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20011293A NO328523B1 (no)	1998-09-15	2001-03-14	Faktor VIIa-inhibitorer, fremgangsmate for fremstilling av slike og farmasoytisk preparat omfattende slike, samt anvendelse av inhibitorene for fremstilling av farmasoytisk preparat.

Country Status (25)

Country	Link
US (1)	US6287794B1 (pl)
EP (2)	EP0987274A1 (pl)
JP (1)	JP4537581B2 (pl)
KR (1)	KR100665490B1 (pl)
CN (1)	CN1203087C (pl)
AR (1)	AR027814A1 (pl)
AT (1)	ATE460424T1 (pl)
AU (1)	AU760580B2 (pl)
BR (1)	BR9913742A (pl)
CA (1)	CA2344048A1 (pl)
CZ (1)	CZ300249B6 (pl)
DE (1)	DE69942123D1 (pl)
HK (1)	HK1040253B (pl)
HU (1)	HUP0103851A3 (pl)
ID (1)	ID28494A (pl)
IL (2)	IL141415A0 (pl)
MY (1)	MY125150A (pl)
NO (1)	NO328523B1 (pl)
NZ (1)	NZ510509A (pl)
PL (1)	PL203227B1 (pl)
RU (1)	RU2223967C2 (pl)
TR (1)	TR200100766T2 (pl)
TW (1)	TW576839B (pl)
WO (1)	WO2000015658A1 (pl)
ZA (1)	ZA200101861B (pl)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0987274A1 (en) *	1998-09-15	2000-03-22	Hoechst Marion Roussel Deutschland GmbH	Factor VIIa Inhibitors
CN100488947C (zh) *	1999-01-13	2009-05-20	杰南技术公司	丝氨酸蛋白酶抑制剂
EP1059302A1 (en) *	1999-06-08	2000-12-13	Aventis Pharma Deutschland GmbH	Factor VIIa inhibitors
DK1222854T3 (da) *	1999-10-01	2011-03-14	Chugai Pharmaceutical Co Ltd	Forebyggelse og behandling af sygdomme forbundet med blodkoagulering
EP1095933A1 (en)	1999-10-30	2001-05-02	Aventis Pharma Deutschland GmbH	Novel N-guanidinoalkylamides, their preparation, their use, and pharmaceutical preparations comprising them
EP1162194A1 (en) *	2000-06-06	2001-12-12	Aventis Pharma Deutschland GmbH	Factor VIIa inhibitory (thio)urea derivatives, their preparation and their use
GB0014134D0 (en) *	2000-06-10	2000-08-02	Astrazeneca Ab	Combination therapy
WO2002034711A1 (en)	2000-10-20	2002-05-02	Biocryst Pharmaceuticals, Inc.	Biaryl compounds as serine protease inhibitors
PL362320A1 (pl)	2000-12-06	2004-10-18	Aventis Pharma Deutschland Gmbh	Pochodne guanidynowe i amidynowe jako inhibitory czynnika XA
EP1364960A4 (en)	2001-02-02	2005-05-18	Chugai Pharmaceutical Co Ltd	PEPTIDE DERIVATIVES
EP1270551A1 (en) *	2001-06-26	2003-01-02	Aventis Pharma Deutschland GmbH	Urea derivatives with antiproteolytic activity
EP1314733A1 (en)	2001-11-22	2003-05-28	Aventis Pharma Deutschland GmbH	Indole-2-carboxamides as factor Xa inhibitors
WO2004043991A2 (en) *	2002-11-13	2004-05-27	Haematologic Technologies, Inc.	Assay for tissue factor and factor viia
US7358268B2 (en)	2002-12-04	2008-04-15	Sanofi-Aventis Deutschland Gmbh	Imidazole derivatives as factor Xa inhibitors
US7429581B2 (en)	2002-12-23	2008-09-30	Sanofi-Aventis Deutschland Gmbh	Pyrazole-derivatives as factor Xa inhibitors
US7223780B2 (en)	2003-05-19	2007-05-29	Sanofi-Aventis Deutschland Gmbh	Triazole-derivatives as blood clotting enzyme factor Xa inhibitors
US7317027B2 (en)	2003-05-19	2008-01-08	Sanofi-Aventis Deutschland Gmbh	Azaindole-derivatives as factor Xa inhibitors
EP1479677A1 (en) *	2003-05-19	2004-11-24	Aventis Pharma Deutschland GmbH	New indole derivatives as factor xa inhibitors
US7741341B2 (en)	2003-05-19	2010-06-22	Sanofi-Aventis Deutschland Gmbh	Benzimidazole-derivatives as factor Xa inhibitors
EP1479675A1 (en)	2003-05-19	2004-11-24	Aventis Pharma Deutschland GmbH	Indazole-derivatives as factor Xa inhibitors
EP1479680A1 (en)	2003-05-19	2004-11-24	Aventis Pharma Deutschland GmbH	Azaindole derivatives as Factor Xa inhibitors
US7250447B2 (en)	2003-05-20	2007-07-31	Genentech, Inc.	Acylsulfamide inhibitors of factor VIIa
WO2004113316A1 (en)	2003-05-20	2004-12-29	Genentech, Inc.	Benzofuran inhibitors of factor viia
EP1568698A1 (en)	2004-02-27	2005-08-31	Aventis Pharma Deutschland GmbH	Pyrrole-derivatives as factor Xa inhibitors
PL1748781T3 (pl) *	2004-05-27	2013-05-31	Baxter Int	Sposoby do leczenia zaburzeń związanych z krwawieniem z zastosowaniem siarczanowanych polisacharydów
WO2008107362A2 (en) *	2007-03-07	2008-09-12	Novo Nordisk Health Care Ag	Stabiliser and inhibitors of factor vii
WO2009007015A1 (en)	2007-07-10	2009-01-15	Sanofi-Aventis	Malonamide derivatives with antithrombotic activity
US8486892B2 (en)	2008-01-23	2013-07-16	Novo Nordisk Health Care Ag	Blood coagulation factor inhibitors
EP2670429B1 (en)	2011-02-04	2018-04-04	Octapharma AG	Method for inactivation/removal of coagulation factors by precipitation
WO2020053773A1 (en) *	2018-09-11	2020-03-19	Anbition S.R.L.	Peptides and medical uses thereof
EP3849582B1 (en) *	2018-09-11	2025-12-31	Anbition S.r.l.	Peptides and their medical uses
BR112021026410A2 (pt)	2019-07-01	2022-02-08	Tonix Pharma Ltd	Anticorpos anti-cd154 e usos dos mesmos
JP2024503625A (ja)	2021-01-06	2024-01-26	トニックスファーマリミテッド	改変された抗ｃｄ１５４抗体により免疫寛容を誘導する方法
GB202209228D0 (en) *	2022-06-23	2022-08-10	Univ Strathclyde	Modified amino acids and uses thereof
WO2025248134A1 (en)	2024-05-31	2025-12-04	Tonix Pharma Limited	Treatment methods comprising administration of modified cd154 antibodies

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5023236A (en) *	1988-04-07	1991-06-11	Corvas, Inc.	Factor VII/VIIA active site inhibitors
EP0391999A4 (en) *	1988-09-23	1991-03-13	Corvas, Inc.	Peptidyl inhibitors of the initiation of coagulation
CA2008116C (en) *	1989-02-23	2001-11-20	Thomas Weller	Glycine derivatives
US5190919A (en) *	1989-11-13	1993-03-02	Board Of Regents, The University Of Texas System	Antihemostatic factor vii peptides
HU206372B (en) *	1990-09-03	1992-10-28	Richter Gedeon Vegyeszet	Process for producing new oligopeptides which selectively inhibit proliferation of haemopoietic cells and pharmaceutical compositions comprising same
US5506134A (en)	1990-10-22	1996-04-09	Corvas International, Inc.	Hypridoma and monoclonal antibody which inhibits blood coagulation tissue factor/factor VIIa complex
US5788965A (en)	1991-02-28	1998-08-04	Novo Nordisk A/S	Modified factor VII
US5833982A (en)	1991-02-28	1998-11-10	Zymogenetics, Inc.	Modified factor VII
SE9301916D0 (sv) *	1993-06-03	1993-06-03	Ab Astra	New peptides derivatives
DK0703923T3 (da) *	1993-06-18	1999-06-21	Nycomed Imaging As	Faktor VII afledte peptider
HUT76346A (en) *	1994-04-26	1997-08-28	Selectide Corp	Factor xa inhibitors
US5849510A (en) *	1994-04-26	1998-12-15	Selectide Corporation	Factor Xa inhibitors
RU2097033C1 (ru) *	1994-09-30	1997-11-27	Московская государственная академия тонкой химической технологии им.М.В.Ломоносова	Имидазолсодержащие ингибиторы катепсин g-индуцированной агрегации тромбоцитов
US5837684A (en) *	1995-06-07	1998-11-17	Nycomed Imaging As	Peptides
DE69717268T2 (de) *	1996-02-22	2003-09-04	Bristol-Myers Squibb Pharma Co., Wilmington	M-amidinophenyl-analoga als faktor-xa-inhibitoren
EP0987274A1 (en) *	1998-09-15	2000-03-22	Hoechst Marion Roussel Deutschland GmbH	Factor VIIa Inhibitors

1998
- 1998-09-15 EP EP98117506A patent/EP0987274A1/en not_active Withdrawn
1999
- 1999-09-02 AU AU59723/99A patent/AU760580B2/en not_active Ceased
- 1999-09-02 ID IDW20010598A patent/ID28494A/id unknown
- 1999-09-02 NZ NZ510509A patent/NZ510509A/xx not_active IP Right Cessation
- 1999-09-02 DE DE69942123T patent/DE69942123D1/de not_active Expired - Lifetime
- 1999-09-02 KR KR1020017003350A patent/KR100665490B1/ko not_active Expired - Fee Related
- 1999-09-02 HK HK02101586.6A patent/HK1040253B/zh not_active IP Right Cessation
- 1999-09-02 JP JP2000570196A patent/JP4537581B2/ja not_active Expired - Fee Related
- 1999-09-02 TR TR2001/00766T patent/TR200100766T2/xx unknown
- 1999-09-02 PL PL346781A patent/PL203227B1/pl not_active IP Right Cessation
- 1999-09-02 HU HU0103851A patent/HUP0103851A3/hu unknown
- 1999-09-02 IL IL14141599A patent/IL141415A0/xx active IP Right Grant
- 1999-09-02 BR BR9913742-9A patent/BR9913742A/pt not_active Application Discontinuation
- 1999-09-02 CZ CZ20010914A patent/CZ300249B6/cs not_active IP Right Cessation
- 1999-09-02 EP EP99969095A patent/EP1114061B1/en not_active Expired - Lifetime
- 1999-09-02 CN CNB998109169A patent/CN1203087C/zh not_active Expired - Fee Related
- 1999-09-02 CA CA002344048A patent/CA2344048A1/en not_active Abandoned
- 1999-09-02 AT AT99969095T patent/ATE460424T1/de not_active IP Right Cessation
- 1999-09-02 WO PCT/EP1999/006449 patent/WO2000015658A1/en not_active Ceased
- 1999-09-02 RU RU2001110086/04A patent/RU2223967C2/ru not_active IP Right Cessation
- 1999-09-13 AR ARP990104586A patent/AR027814A1/es active IP Right Grant
- 1999-09-14 US US09/395,572 patent/US6287794B1/en not_active Expired - Lifetime
- 1999-09-14 MY MYPI99003984A patent/MY125150A/en unknown
- 1999-09-20 TW TW088115707A patent/TW576839B/zh active
2001
- 2001-02-13 IL IL141415A patent/IL141415A/en not_active IP Right Cessation
- 2001-03-06 ZA ZA200101861A patent/ZA200101861B/en unknown
- 2001-03-14 NO NO20011293A patent/NO328523B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
CZ300249B6 (cs)	2009-04-01
AU5972399A (en)	2000-04-03
KR100665490B1 (ko)	2007-01-10
CZ2001914A3 (en)	2001-06-13
WO2000015658A1 (en)	2000-03-23
HUP0103851A3 (en)	2002-05-28
TW576839B (en)	2004-02-21
MY125150A (en)	2006-07-31
ID28494A (id)	2001-05-31
CA2344048A1 (en)	2000-03-23
PL346781A1 (en)	2002-02-25
ATE460424T1 (de)	2010-03-15
DE69942123D1 (de)	2010-04-22
ZA200101861B (en)	2001-10-22
HK1040253B (zh)	2005-09-02
RU2223967C2 (ru)	2004-02-20
CN1318069A (zh)	2001-10-17
HUP0103851A2 (hu)	2002-04-29
NO20011293D0 (no)	2001-03-14
AR027814A1 (es)	2003-04-16
HK1040253A1 (en)	2002-05-31
EP0987274A1 (en)	2000-03-22
NO20011293L (no)	2001-05-04
EP1114061A1 (en)	2001-07-11
AU760580B2 (en)	2003-05-15
BR9913742A (pt)	2001-06-05
PL203227B1 (pl)	2009-09-30
CN1203087C (zh)	2005-05-25
US6287794B1 (en)	2001-09-11
IL141415A0 (en)	2002-03-10
JP2002524571A (ja)	2002-08-06
TR200100766T2 (tr)	2001-10-22
JP4537581B2 (ja)	2010-09-01
KR20010075130A (ko)	2001-08-09
IL141415A (en)	2006-09-05
EP1114061B1 (en)	2010-03-10
NZ510509A (en)	2002-09-27

Legal Events

Date	Code	Title	Description
2011-05-09	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
US6287794B1 (en)	2001-09-11	Factor Vlla inhibitors
EP0699074B1 (en)	2002-11-13	Thrombin inhibitors
US5371072A (en)	1994-12-06	Asp-Pro-Arg α-keto-amide enzyme inhibitors
US5672582A (en)	1997-09-30	Thrombin inhibitors
AU601801B2 (en)	1990-09-20	Anticoagulant peptides
JPH08508716A (ja)	1996-09-17	血栓症のインヒビター
JPH10503477A (ja)	1998-03-31	第Ｘａ因子インヒビター
WO1991001331A1 (en)	1991-02-07	Small cyclic platelet aggregation inhibitors
KR19980703173A (ko)	1998-10-15	히루딘의 아미노산 서열에 기초한 트롬빈 억제제
HRP20010912A2 (en)	2003-04-30	FACTOR VIIa INHIBITORS
RU2175327C2 (ru)	2001-10-27	Производные имидазо[1,5-а]пиридина как ингибиторы серинпротеаз и фармацевтическая композиция
US20060276402A1 (en)	2006-12-07	Synthetic peptide inhibitors of thrombin and thrombin activation of protease activated receptors 1 and 4
US5856309A (en)	1999-01-05	Amidinopyrroline derivatives, processes for their production and pharmaceutical agents containing these compounds
MXPA01002400A (en)	2001-11-21	FACTOR VIIa INHIBITORS
EP1425009A2 (en)	2004-06-09	Peptide arginals and methods for treating disseminated intravascular coagulation
AU2002331654A1 (en)	2003-05-29	Peptide arginals and methods for treating disseminated intravascular coagulation
NO300504B1 (no)	1997-06-09	Forbindelse og terapeutisk preparat omfattende denne
HK1009454B (en)	2001-04-27	Imidazo(1.5a) pyridine derived serine protease inhibitors