LT4972B - Benzenamine derivatives as anti-coagulants - Google Patents

Benzenamine derivatives as anti-coagulants Download PDF

Info

Publication number: LT4972B
Authority: LT; Lithuania
Prior art keywords: oxy; piperidin; benzenamine; prop; amidinophenyl
Prior art date: 1999-07-30

Application number

LT2002009A

Other languages

English (en)

Lithuanian (lt)

Other versions

LT2002009A (en

Inventor

William J. Guilford

Steven T. Sakata

Kenneth J. Shaw

Shung Wu

Wei Xu

Zuchun Zhao

Original Assignee

Berlex Laboratories,Inc.

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.)

1999-07-30

Filing date

2002-01-24

Publication date

2002-11-25

2002-01-24 Application filed by Berlex Laboratories,Inc. filed Critical Berlex Laboratories,Inc.

2002-07-25 Publication of LT2002009A publication Critical patent/LT2002009A/xx

2002-11-25 Publication of LT4972B publication Critical patent/LT4972B/lt

Links

239000003146 anticoagulant agent Substances 0.000 title claims abstract description 12
229940127219 anticoagulant drug Drugs 0.000 title claims abstract description 12
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical class NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 title claims description 58
150000001875 compounds Chemical class 0.000 claims abstract description 374
-1 aminocarbonylmethyl Chemical group 0.000 claims description 211
125000000217 alkyl group Chemical group 0.000 claims description 72
229910052739 hydrogen Inorganic materials 0.000 claims description 55
239000001257 hydrogen Substances 0.000 claims description 55
239000000243 solution Substances 0.000 claims description 52
238000006243 chemical reaction Methods 0.000 claims description 51
150000002431 hydrogen Chemical class 0.000 claims description 48
238000000034 method Methods 0.000 claims description 43
239000000203 mixture Substances 0.000 claims description 42
108010074860 Factor Xa Proteins 0.000 claims description 41
238000002360 preparation method Methods 0.000 claims description 39
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
150000003839 salts Chemical class 0.000 claims description 37
125000003545 alkoxy group Chemical group 0.000 claims description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 32
125000003118 aryl group Chemical group 0.000 claims description 32
125000003710 aryl alkyl group Chemical group 0.000 claims description 30
238000012360 testing method Methods 0.000 claims description 28
108090000190 Thrombin Proteins 0.000 claims description 25
238000003556 assay Methods 0.000 claims description 25
229960004072 thrombin Drugs 0.000 claims description 25
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 23
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 21
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 20
108010000499 Thromboplastin Proteins 0.000 claims description 19
102000002262 Thromboplastin Human genes 0.000 claims description 19
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 14
125000001188 haloalkyl group Chemical group 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 13
239000003112 inhibitor Substances 0.000 claims description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
102000004190 Enzymes Human genes 0.000 claims description 12
108090000790 Enzymes Proteins 0.000 claims description 12
125000004663 dialkyl amino group Chemical group 0.000 claims description 12
229940088598 enzyme Drugs 0.000 claims description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 11
230000015271 coagulation Effects 0.000 claims description 11
238000005345 coagulation Methods 0.000 claims description 11
102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 10
108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 10
230000000694 effects Effects 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
229960000187 tissue plasminogen activator Drugs 0.000 claims description 10
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 9
125000004181 carboxyalkyl group Chemical group 0.000 claims description 9
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
AZYUEGYLCDGFFD-UHFFFAOYSA-N 4-hydroxy-3-prop-1-enylbenzenecarboximidamide Chemical compound OC1=CC=C(C=C1C=CC)C(N)=N AZYUEGYLCDGFFD-UHFFFAOYSA-N 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 7
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 7
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
239000000872 buffer Substances 0.000 claims description 7
125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 7
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
108010094028 Prothrombin Proteins 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
235000019359 magnesium stearate Nutrition 0.000 claims description 6
238000003756 stirring Methods 0.000 claims description 6
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MUHMMRCCRMYABT-UHFFFAOYSA-N C1CN(C(=N)C)CCC1OC(C(=C1)F)=C(F)C=C1NCC=CC1=CC=CC(C(N)=N)=C1 Chemical compound C1CN(C(=N)C)CCC1OC(C(=C1)F)=C(F)C=C1NCC=CC1=CC=CC(C(N)=N)=C1 MUHMMRCCRMYABT-UHFFFAOYSA-N 0.000 claims description 5
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 claims description 5
102100027378 Prothrombin Human genes 0.000 claims description 5
239000002775 capsule Substances 0.000 claims description 5
239000003153 chemical reaction reagent Substances 0.000 claims description 5
WEQMEZGOGHSVBK-UHFFFAOYSA-N ethyl 5-[bis[3-(3-carbamimidoylphenyl)prop-2-enyl]amino]-2-piperidin-4-yloxybenzoate Chemical compound CCOC(=O)C1=CC(N(CC=CC=2C=C(C=CC=2)C(N)=N)CC=CC=2C=C(C=CC=2)C(N)=N)=CC=C1OC1CCNCC1 WEQMEZGOGHSVBK-UHFFFAOYSA-N 0.000 claims description 5
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229940039716 prothrombin Drugs 0.000 claims description 5
239000011780 sodium chloride Substances 0.000 claims description 5
PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 claims description 4
WSZSQGHQATUDOF-UHFFFAOYSA-N C1CN(C(=N)C)CCC1OC(C(=C1)C(F)(F)F)=CC=C1NCC=CC1=CC(C(N)=N)=CC=C1O Chemical compound C1CN(C(=N)C)CCC1OC(C(=C1)C(F)(F)F)=CC=C1NCC=CC1=CC(C(N)=N)=CC=C1O WSZSQGHQATUDOF-UHFFFAOYSA-N 0.000 claims description 4
KQUXRDJYXVLBCE-UHFFFAOYSA-N C1CN(C(=N)C)CCC1OC1=CC=C(N(CC=CC=2C(=CC=C(C=2)C(N)=N)O)C(=O)CCC(O)=O)C=C1C(O)=O Chemical compound C1CN(C(=N)C)CCC1OC1=CC=C(N(CC=CC=2C(=CC=C(C=2)C(N)=N)O)C(=O)CCC(O)=O)C=C1C(O)=O KQUXRDJYXVLBCE-UHFFFAOYSA-N 0.000 claims description 4
KALYGJFFUOXJMI-UHFFFAOYSA-N C1CN(C(=N)C)CCC1OC1=CC=C(N(CC=CC=2C(=CC=C(C=2)C(N)=N)O)CC=2C=CC=CC=2)C=C1C(F)(F)F Chemical compound C1CN(C(=N)C)CCC1OC1=CC=C(N(CC=CC=2C(=CC=C(C=2)C(N)=N)O)CC=2C=CC=CC=2)C=C1C(F)(F)F KALYGJFFUOXJMI-UHFFFAOYSA-N 0.000 claims description 4
CNDXACJVAMNJDO-UHFFFAOYSA-N C1CN(C(=N)C)CCC1OC1=CC=C(N(CC=CC=2C=C(C=CC=2)C(N)=N)CC(O)=O)C=C1[N+]([O-])=O Chemical compound C1CN(C(=N)C)CCC1OC1=CC=C(N(CC=CC=2C=C(C=CC=2)C(N)=N)CC(O)=O)C=C1[N+]([O-])=O CNDXACJVAMNJDO-UHFFFAOYSA-N 0.000 claims description 4
OSPGRQASVCIVMN-UHFFFAOYSA-N CC1=C(C=CC=C1N)CCCC2=C(C=CC(=C2)C(=N)N)O Chemical compound CC1=C(C=CC=C1N)CCCC2=C(C=CC(=C2)C(=N)N)O OSPGRQASVCIVMN-UHFFFAOYSA-N 0.000 claims description 4
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229910052786 argon Inorganic materials 0.000 claims description 4
238000001727 in vivo Methods 0.000 claims description 4
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125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
239000000047 product Substances 0.000 claims description 4
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235000019698 starch Nutrition 0.000 claims description 4
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VSVWHCJWQRAHSV-UHFFFAOYSA-N 3-[3-(2-aminophenyl)prop-1-enyl]benzenecarboximidamide Chemical compound NC(=N)C1=CC=CC(C=CCC=2C(=CC=CC=2)N)=C1 VSVWHCJWQRAHSV-UHFFFAOYSA-N 0.000 claims description 3
TYGCRUSCHGBIBW-UHFFFAOYSA-N 3-[3-[4-(1-ethanimidoylpiperidin-4-yl)oxy-3-(trifluoromethyl)anilino]prop-1-enyl]benzenecarboximidamide Chemical compound C1CN(C(=N)C)CCC1OC(C(=C1)C(F)(F)F)=CC=C1NCC=CC1=CC=CC(C(N)=N)=C1 TYGCRUSCHGBIBW-UHFFFAOYSA-N 0.000 claims description 3
AEXABJFYMNKEOB-UHFFFAOYSA-N 3-[3-[4-(1-ethanimidoylpiperidin-4-yl)oxy-3-fluoroanilino]prop-1-enyl]benzenecarboximidamide Chemical compound C1CN(C(=N)C)CCC1OC(C(=C1)F)=CC=C1NCC=CC1=CC=CC(C(N)=N)=C1 AEXABJFYMNKEOB-UHFFFAOYSA-N 0.000 claims description 3
LQGGRNZLSKPEHI-UHFFFAOYSA-N 3-[3-[4-(1-ethanimidoylpiperidin-4-yl)oxyanilino]prop-1-enyl]benzenecarboximidamide Chemical compound C1CN(C(=N)C)CCC1OC(C=C1)=CC=C1NCC=CC1=CC=CC(C(N)=N)=C1 LQGGRNZLSKPEHI-UHFFFAOYSA-N 0.000 claims description 3
NKSLZFJLSABSEY-UHFFFAOYSA-N 4-[N-[3-(5-carbamimidoyl-2-hydroxyphenyl)prop-2-enyl]-4-(1-methylpiperidin-4-yl)oxy-3-(trifluoromethyl)anilino]-4-oxobutanoic acid Chemical compound C1CN(C)CCC1OC1=CC=C(N(CC=CC=2C(=CC=C(C=2)C(N)=N)O)C(=O)CCC(O)=O)C=C1C(F)(F)F NKSLZFJLSABSEY-UHFFFAOYSA-N 0.000 claims description 3
OUGINLCWXFWQDK-UHFFFAOYSA-N 4-hydroxy-3-[3-(4-piperidin-4-yloxyanilino)propyl]benzenecarboximidamide Chemical compound NC(=N)C1=CC=C(O)C(CCCNC=2C=CC(OC3CCNCC3)=CC=2)=C1 OUGINLCWXFWQDK-UHFFFAOYSA-N 0.000 claims description 3
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239000012141 concentrate Substances 0.000 claims description 3
PZVTYTRORJEOPM-UHFFFAOYSA-N ethyl 5-[3-(3-carbamimidoylphenyl)prop-2-enylamino]-2-(1-ethanimidoylpiperidin-4-yl)oxybenzoate Chemical compound C=1C=C(OC2CCN(CC2)C(C)=N)C(C(=O)OCC)=CC=1NCC=CC1=CC=CC(C(N)=N)=C1 PZVTYTRORJEOPM-UHFFFAOYSA-N 0.000 claims description 3
OLXRELWTJHLORR-UHFFFAOYSA-N ethyl 5-[3-(3-carbamimidoylphenyl)prop-2-enylamino]-2-piperidin-4-yloxybenzoate Chemical compound C=1C=C(OC2CCNCC2)C(C(=O)OCC)=CC=1NCC=CC1=CC=CC(C(N)=N)=C1 OLXRELWTJHLORR-UHFFFAOYSA-N 0.000 claims description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
108010014806 prothrombinase complex Proteins 0.000 claims description 3
UENUEONRMNAUOE-UHFFFAOYSA-N 3-[2-methyl-3-(4-piperidin-4-yloxyanilino)prop-1-enyl]-4-phenylmethoxybenzenecarboximidamide Chemical compound C=1C(C(N)=N)=CC=C(OCC=2C=CC=CC=2)C=1C=C(C)CNC(C=C1)=CC=C1OC1CCNCC1 UENUEONRMNAUOE-UHFFFAOYSA-N 0.000 claims description 2
QSDWNTLRSZADID-UHFFFAOYSA-N 3-[3-[4-(1-ethanimidoylpiperidin-4-yl)oxy-3-nitroanilino]-2-methylprop-1-enyl]benzenecarboximidamide Chemical compound C=1C=CC(C(N)=N)=CC=1C=C(C)CNC(C=C1[N+]([O-])=O)=CC=C1OC1CCN(C(C)=N)CC1 QSDWNTLRSZADID-UHFFFAOYSA-N 0.000 claims description 2
YNYVXZDENRCRMJ-UHFFFAOYSA-N 3-[3-[4-(1-ethanimidoylpiperidin-4-yl)oxy-3-nitroanilino]prop-1-enyl]benzenecarboximidamide Chemical compound C1CN(C(=N)C)CCC1OC(C(=C1)[N+]([O-])=O)=CC=C1NCC=CC1=CC=CC(C(N)=N)=C1 YNYVXZDENRCRMJ-UHFFFAOYSA-N 0.000 claims description 2
XFCWLCSPCGJGDD-UHFFFAOYSA-N 3-[3-[4-(1-ethanimidoylpiperidin-4-yl)oxy-n-propan-2-ylanilino]prop-1-enyl]benzenecarboximidamide Chemical compound C=1C=C(OC2CCN(CC2)C(C)=N)C=CC=1N(C(C)C)CC=CC1=CC=CC(C(N)=N)=C1 XFCWLCSPCGJGDD-UHFFFAOYSA-N 0.000 claims description 2
XZUDLMLPCQEKES-UHFFFAOYSA-N 3-[3-[[4-(1-ethanimidoylpiperidin-4-yl)oxy-3-nitroanilino]methyl]phenyl]benzenecarboximidamide Chemical compound C1CN(C(=N)C)CCC1OC(C(=C1)[N+]([O-])=O)=CC=C1NCC1=CC=CC(C=2C=C(C=CC=2)C(N)=N)=C1 XZUDLMLPCQEKES-UHFFFAOYSA-N 0.000 claims description 2
OZKRKCGCMMORQI-UHFFFAOYSA-N 3-[3-[[4-piperidin-4-yloxy-3-(trifluoromethyl)anilino]methyl]phenyl]benzenecarboximidamide Chemical compound NC(=N)C1=CC=CC(C=2C=C(CNC=3C=C(C(OC4CCNCC4)=CC=3)C(F)(F)F)C=CC=2)=C1 OZKRKCGCMMORQI-UHFFFAOYSA-N 0.000 claims description 2
GLBXBDIEHKDXLC-UHFFFAOYSA-N 4-[4-[3-(5-carbamimidoyl-2-hydroxyphenyl)prop-2-enylamino]-2-(trifluoromethyl)phenoxy]piperidine-1-carboxamide Chemical compound NC(=N)C1=CC=C(O)C(C=CCNC=2C=C(C(OC3CCN(CC3)C(N)=O)=CC=2)C(F)(F)F)=C1 GLBXBDIEHKDXLC-UHFFFAOYSA-N 0.000 claims description 2
GPSVRAJPFXFFLP-UHFFFAOYSA-N 4-[N-[3-(5-carbamimidoyl-2-hydroxyphenyl)prop-2-enyl]-4-piperidin-4-yloxy-3-(trifluoromethyl)anilino]-4-oxobutanoic acid Chemical compound NC(=N)C1=CC=C(O)C(C=CCN(C(=O)CCC(O)=O)C=2C=C(C(OC3CCNCC3)=CC=2)C(F)(F)F)=C1 GPSVRAJPFXFFLP-UHFFFAOYSA-N 0.000 claims description 2
JZSSWBLMVMMVGJ-UHFFFAOYSA-N 4-hydroxy-3-[3-[4-(oxan-4-yloxy)-3-(trifluoromethyl)anilino]prop-1-enyl]benzenecarboximidamide Chemical compound NC(=N)C1=CC=C(O)C(C=CCNC=2C=C(C(OC3CCOCC3)=CC=2)C(F)(F)F)=C1 JZSSWBLMVMMVGJ-UHFFFAOYSA-N 0.000 claims description 2
GCBBPCAWKGRDMM-UHFFFAOYSA-N 5-[3-(3-carbamimidoylphenyl)prop-2-enyl-(3-carboxypropanoyl)amino]-2-piperidin-4-yloxybenzoic acid Chemical compound NC(=N)C1=CC=CC(C=CCN(C(=O)CCC(O)=O)C=2C=C(C(OC3CCNCC3)=CC=2)C(O)=O)=C1 GCBBPCAWKGRDMM-UHFFFAOYSA-N 0.000 claims description 2
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125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000003226 mitogen Substances 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000000399 orthopedic effect Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
239000006179 pH buffering agent Substances 0.000 description 1
UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
125000001639 phenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
229920002523 polyethylene Glycol 1000 Polymers 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
239000000473 propyl gallate Substances 0.000 description 1
235000010388 propyl gallate Nutrition 0.000 description 1
229940075579 propyl gallate Drugs 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
230000006965 reversible inhibition Effects 0.000 description 1
229940085605 saccharin sodium Drugs 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229940035044 sorbitan monolaurate Drugs 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
238000011477 surgical intervention Methods 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
UKJJTUFZQVWVPD-UHFFFAOYSA-N tert-butyl 4-(4-amino-2-nitrophenoxy)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=C(N)C=C1[N+]([O-])=O UKJJTUFZQVWVPD-UHFFFAOYSA-N 0.000 description 1
OTVCSUPBBHZHNS-UHFFFAOYSA-N tert-butyl 4-(4-amino-3-methoxycarbonylphenoxy)piperidine-1-carboxylate Chemical compound C1=C(N)C(C(=O)OC)=CC(OC2CCN(CC2)C(=O)OC(C)(C)C)=C1 OTVCSUPBBHZHNS-UHFFFAOYSA-N 0.000 description 1
VHBFMBRLCBGTSZ-UHFFFAOYSA-N tert-butyl 4-[4-[3-(3-cyanophenyl)prop-2-enyl-(2-methoxy-2-oxoethyl)amino]-2-nitrophenoxy]piperidine-1-carboxylate Chemical compound C=1C=C(OC2CCN(CC2)C(=O)OC(C)(C)C)C([N+]([O-])=O)=CC=1N(CC(=O)OC)CC=CC1=CC=CC(C#N)=C1 VHBFMBRLCBGTSZ-UHFFFAOYSA-N 0.000 description 1
YKVLEHMPMVKCKI-UHFFFAOYSA-N tert-butyl 4-[4-[3-(3-cyanophenyl)prop-2-enylamino]-2-nitrophenoxy]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC(C(=C1)[N+]([O-])=O)=CC=C1NCC=CC1=CC=CC(C#N)=C1 YKVLEHMPMVKCKI-UHFFFAOYSA-N 0.000 description 1
PBUYTZFWSSKZCD-UHFFFAOYSA-N tert-butyl 4-[4-nitro-2-(trifluoromethyl)phenoxy]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=C([N+]([O-])=O)C=C1C(F)(F)F PBUYTZFWSSKZCD-UHFFFAOYSA-N 0.000 description 1
RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
229960004559 theobromine Drugs 0.000 description 1
239000003868 thrombin inhibitor Substances 0.000 description 1
230000002537 thrombolytic effect Effects 0.000 description 1
230000036964 tight binding Effects 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
229940117013 triethanolamine oleate Drugs 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
230000002792 vascular Effects 0.000 description 1
PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/02—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Hematology (AREA)
Diabetes (AREA)
Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Silver Salt Photography Or Processing Solution Therefor (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pyrane Compounds (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Separation Of Suspended Particles By Flocculating Agents (AREA)

LT2002009A 1999-07-30 2002-01-24 Benzenamine derivatives as anti-coagulants LT4972B (lt)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US14657299P	1999-07-30	1999-07-30
US09/624,519 US6350761B1 (en)	1999-07-30	2000-07-24	Benzenamine derivatives as anti-coagulants

Publications (2)

Publication Number	Publication Date
LT2002009A LT2002009A (en)	2002-07-25
LT4972B true LT4972B (lt)	2002-11-25

Family

ID=26844067

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LT2002009A LT4972B (lt)	1999-07-30	2002-01-24	Benzenamine derivatives as anti-coagulants

Country Status (23)

Country	Link
US (1)	US6350761B1 (es)
EP (1)	EP1200405A1 (es)
JP (1)	JP2003506353A (es)
KR (1)	KR20020068494A (es)
CN (1)	CN1367777A (es)
AU (1)	AU766820B2 (es)
BR (1)	BR0013292A (es)
CA (1)	CA2380029A1 (es)
CZ (1)	CZ2002346A3 (es)
EE (1)	EE200200050A (es)
HK (1)	HK1049482A1 (es)
HR (1)	HRP20020185A2 (es)
HU (1)	HUP0202234A3 (es)
IL (2)	IL147746A0 (es)
LT (1)	LT4972B (es)
LV (1)	LV12844B (es)
MX (1)	MXPA02001065A (es)
NO (1)	NO20020457L (es)
NZ (1)	NZ516804A (es)
PL (1)	PL357871A1 (es)
SI (1)	SI20815A (es)
SK (1)	SK1252002A3 (es)
WO (1)	WO2001009093A1 (es)

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US6262088B1 (en)	1998-11-19	2001-07-17	Berlex Laboratories, Inc.	Polyhydroxylated monocyclic N-heterocyclic derivatives as anti-coagulants
PL354619A1 (en) *	1999-10-28	2004-02-09	Sankyo Company, Limited	Benzamidine derivatives
AU2004203154B2 (en) *	1999-10-28	2006-06-01	Sankyo Company, Limited	Benzamidine derivatives
US20020065303A1 (en) *	2000-02-01	2002-05-30	Bing-Yan Zhu	Bivalent phenylene inhibitors of factor Xa
DE10110325A1 (de) *	2001-03-03	2002-09-05	Merck Patent Gmbh	Phenylderivate 2
RU2256652C1 (ru)	2001-04-05	2005-07-20	Санкио Компани, Лимитед	Соединение, фармацевтическая композиция, применение, способ предупреждения или лечения заболеваний
HUE025683T2 (hu)	2002-12-03	2016-04-28	Pharmacyclics Llc	VIIA faktor inhibitor 2-(2-hidroxi-bifenil-3-il)-1H-benzoimidazol-5-karboxamidin-származékok
US7678785B2 (en) *	2006-07-24	2010-03-16	Ucb Pharma S.A.	Substituted aniline derivatives
MX2010006045A (es) *	2007-12-12	2010-06-23	Amgen Inc	Inhibidores de transportador de glicina-1.
EP2602248A1 (en)	2011-12-05	2013-06-12	University Of Leicester	Novel pyrrole compounds
US11596612B1 (en)	2022-03-08	2023-03-07	PTC Innovations, LLC	Topical anesthetics

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2000
- 2000-07-24 US US09/624,519 patent/US6350761B1/en not_active Expired - Fee Related
- 2000-07-27 NZ NZ516804A patent/NZ516804A/en unknown
- 2000-07-27 KR KR1020027001272A patent/KR20020068494A/ko not_active Withdrawn
- 2000-07-27 HU HU0202234A patent/HUP0202234A3/hu unknown
- 2000-07-27 PL PL00357871A patent/PL357871A1/xx not_active Application Discontinuation
- 2000-07-27 MX MXPA02001065A patent/MXPA02001065A/es unknown
- 2000-07-27 WO PCT/US2000/020390 patent/WO2001009093A1/en not_active Ceased
- 2000-07-27 CA CA002380029A patent/CA2380029A1/en not_active Abandoned
- 2000-07-27 BR BR0013292-6A patent/BR0013292A/pt not_active IP Right Cessation
- 2000-07-27 SK SK125-2002A patent/SK1252002A3/sk unknown
- 2000-07-27 JP JP2001514297A patent/JP2003506353A/ja active Pending
- 2000-07-27 CZ CZ2002346A patent/CZ2002346A3/cs unknown
- 2000-07-27 HK HK03101486.6A patent/HK1049482A1/zh unknown
- 2000-07-27 CN CN00811086A patent/CN1367777A/zh active Pending
- 2000-07-27 EE EEP200200050A patent/EE200200050A/xx unknown
- 2000-07-27 AU AU63805/00A patent/AU766820B2/en not_active Ceased
- 2000-07-27 IL IL14774600A patent/IL147746A0/xx not_active IP Right Cessation
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- 2000-07-27 EP EP00950745A patent/EP1200405A1/en not_active Withdrawn
2002
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Publication number	Publication date
NO20020457D0 (no)	2002-01-29
CA2380029A1 (en)	2001-02-08
SK1252002A3 (en)	2002-08-06
MXPA02001065A (es)	2002-10-31
IL147746A0 (en)	2002-08-14
NZ516804A (en)	2003-08-29
LT2002009A (en)	2002-07-25
NO20020457L (no)	2002-03-27
LV12844B (en)	2002-11-20
IL147746A (en)	2007-02-11
HUP0202234A2 (en)	2002-10-28
BR0013292A (pt)	2002-04-02
AU766820B2 (en)	2003-10-23
AU6380500A (en)	2001-02-19
SI20815A (sl)	2002-08-31
JP2003506353A (ja)	2003-02-18
HUP0202234A3 (en)	2005-02-28
EP1200405A1 (en)	2002-05-02
PL357871A1 (en)	2004-07-26
US6350761B1 (en)	2002-02-26
EE200200050A (et)	2003-04-15
CN1367777A (zh)	2002-09-04
WO2001009093A8 (en)	2005-11-10
CZ2002346A3 (cs)	2002-06-12
HRP20020185A2 (en)	2004-02-29
WO2001009093A1 (en)	2001-02-08
KR20020068494A (ko)	2002-08-27
HK1049482A1 (zh)	2003-05-16

Publication	Publication Date	Title
US6495684B2 (en)	2002-12-17	Polyhydroxylated monocyclic N-heterocyclic derivatives as anti-coagulants
EP0865281B1 (en)	2002-04-03	Naphthyl-substituted benzimidazole derivatives as anticoagulants
AU760370B2 (en)	2003-05-15	Aryl and heterocyclyl substituted pyrimidine derivatives as anti-coagulants
LT4972B (lt)	2002-11-25	Benzenamine derivatives as anti-coagulants
BG106363A (bg)	2002-10-31	Бензенаминови производни като анти-коагуланти

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