JP2003524001A5 - - Google Patents
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- JP2003524001A5 JP2003524001A5 JP2001562517A JP2001562517A JP2003524001A5 JP 2003524001 A5 JP2003524001 A5 JP 2003524001A5 JP 2001562517 A JP2001562517 A JP 2001562517A JP 2001562517 A JP2001562517 A JP 2001562517A JP 2003524001 A5 JP2003524001 A5 JP 2003524001A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- benzyl
- formula
- hydrogen
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 229910052739 hydrogen Inorganic materials 0.000 description 52
- 239000001257 hydrogen Substances 0.000 description 52
- 150000001875 compounds Chemical class 0.000 description 50
- -1 4-carbamimidoyl-benzyl Chemical group 0.000 description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- 150000003839 salts Chemical class 0.000 description 15
- 150000001450 anions Chemical class 0.000 description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 10
- 239000000203 mixture Substances 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 7
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 6
- 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 6
- 150000002431 hydrogen Chemical group 0.000 description 6
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 5
- 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 5
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
- PNPPWLHLOSWOSY-MHTYAFTESA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-n'-benzyl-2-[(4-carbamimidoylphenyl)methyl]propanediamide;2,2,2-trifluoroacetic acid Chemical class OC(=O)C(F)(F)F.N([C@H](C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)C1CCCCC1)C(=O)C(C(=O)NCC=1C=CC=CC=1)CC1=CC=C(C(N)=N)C=C1 PNPPWLHLOSWOSY-MHTYAFTESA-N 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 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
- 208000005189 Embolism Diseases 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 3
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 3
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 2
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- XWODQEWOAFLMGW-MHTYAFTESA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-n'-benzyl-2-[[4-[(z)-n'-hydroxycarbamimidoyl]phenyl]methyl]propanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@H](C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)C1CCCCC1)C(=O)C(C(=O)NCC=1C=CC=CC=1)CC1=CC=C(C(=N)NO)C=C1 XWODQEWOAFLMGW-MHTYAFTESA-N 0.000 description 2
- AGTWMPCGSYNEBL-NZZIGVLWSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)NCCC[C@@H](C(N)=O)NC(=O)[C@H](CCCC)NC(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 AGTWMPCGSYNEBL-NZZIGVLWSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- APCJUHZGIFNYHW-AKQSQHNNSA-N (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound N([C@@H](C1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 APCJUHZGIFNYHW-AKQSQHNNSA-N 0.000 description 1
- XXUAYBLKRXHDJV-HGDDKUDHSA-N (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]-3-cyclohexylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CC1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 XXUAYBLKRXHDJV-HGDDKUDHSA-N 0.000 description 1
- PGIXMLLCCPHCCZ-NZZIGVLWSA-N (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCC)NC(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 PGIXMLLCCPHCCZ-NZZIGVLWSA-N 0.000 description 1
- DQVMQOOFTVHQGO-WBLNWVLRSA-N (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(methylamino)-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](C1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)C(C(=O)NC)CC1=CC=C(C(N)=N)C=C1 DQVMQOOFTVHQGO-WBLNWVLRSA-N 0.000 description 1
- GQHZXDWTCGXGIB-MHTYAFTESA-N (2s)-2-[[(2s)-2-[[3-(benzylamino)-2-[(4-carbamimidoylphenyl)methyl]-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@H](C(=O)N[C@@H](CCCNC(=N)N)C(O)=O)C1CCCCC1)C(=O)C(C(=O)NCC=1C=CC=CC=1)CC1=CC=C(C(N)=N)C=C1 GQHZXDWTCGXGIB-MHTYAFTESA-N 0.000 description 1
- BRAMBTDGZGHOES-MHTYAFTESA-N (2s)-2-[[(2s)-2-[[3-(benzylamino)-2-[(4-carbamimidoylphenyl)methyl]-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid;ethyl 2,2,2-trifluoroacetate Chemical compound CCOC(=O)C(F)(F)F.N([C@H](C(=O)N[C@@H](CCCNC(=N)N)C(O)=O)C1CCCCC1)C(=O)C(C(=O)NCC=1C=CC=CC=1)CC1=CC=C(C(N)=N)C=C1 BRAMBTDGZGHOES-MHTYAFTESA-N 0.000 description 1
- SMUZJYKSGHPJRV-DCYPJBMNSA-N (2s)-2-[[(2s)-2-[[3-[benzyl(methyl)amino]-2-[(4-carbamimidoylphenyl)methyl]-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C=1C=C(C(N)=N)C=CC=1CC(C(=O)N[C@@H](C1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)N(C)CC1=CC=CC=C1 SMUZJYKSGHPJRV-DCYPJBMNSA-N 0.000 description 1
- GLZOSBAYSOEXSG-BSOSBYQFSA-N (4s)-5-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]-5-oxopentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 GLZOSBAYSOEXSG-BSOSBYQFSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 1
- IDAPKXJFANBFBA-ILZVRDPESA-N 2-[(4-aminophenyl)methyl]-n-[(1s)-2-[[(2s)-1-[[(2s)-1-[(2s)-2-carbamoylpyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-n',n'-di(propan-2-yl)propanediamide Chemical compound N([C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(N)=O)C1CCCCC1)C(=O)C(C(=O)N(C(C)C)C(C)C)CC1=CC=C(N)C=C1 IDAPKXJFANBFBA-ILZVRDPESA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 206010038563 Reocclusion Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 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
- 239000002253 acid Substances 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
- 238000002399 angioplasty Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000009852 coagulant defect Effects 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- RQEROSMDTGDFBB-GCUDBOHNSA-N ethyl (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoate;hydrochloride Chemical compound Cl.N([C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)OCC)C1CCCCC1)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 RQEROSMDTGDFBB-GCUDBOHNSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- WHBHOTQKYDCLBX-WBLNWVLRSA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-2-[(4-carbamimidoylphenyl)methyl]-n'-methylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](C1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)NC)CC1=CC=C(C(N)=N)C=C1 WHBHOTQKYDCLBX-WBLNWVLRSA-N 0.000 description 1
- IOXIWQMVXKYNKP-YFGYHPHZSA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-n'-benzyl-2-[(4-carbamimidoylphenyl)methyl]-n'-methylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C(C(N)=N)C=CC=1CC(C(=O)N[C@@H](C1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)N(C)CC1=CC=CC=C1 IOXIWQMVXKYNKP-YFGYHPHZSA-N 0.000 description 1
- HMLRTAJDZQXHMS-WBLNWVLRSA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxo-1-phenylethyl]-2-[(4-carbamimidoylphenyl)methyl]-n'-methylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@H](C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C=1C=CC=CC=1)C(=O)C(C(=O)NC)CC1=CC=C(C(N)=N)C=C1 HMLRTAJDZQXHMS-WBLNWVLRSA-N 0.000 description 1
- SYBMAVPFCGYHCI-HGDDKUDHSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 SYBMAVPFCGYHCI-HGDDKUDHSA-N 0.000 description 1
- FVPDKVVUQVGXCM-RWVUOVKPSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n'-methylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)NCCC[C@@H](C(N)=O)NC(=O)[C@H](CCCC)NC(=O)C(C(=O)NC)CC1=CC=C(C(N)=N)C=C1 FVPDKVVUQVGXCM-RWVUOVKPSA-N 0.000 description 1
- AYOIHMIBZZSKMZ-HGDDKUDHSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-(4-aminophenyl)-1-oxopropan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CC=1C=CC(N)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 AYOIHMIBZZSKMZ-HGDDKUDHSA-N 0.000 description 1
- JUOFXQJVVIEERS-HGDDKUDHSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CC1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 JUOFXQJVVIEERS-HGDDKUDHSA-N 0.000 description 1
- AGHMAUIWCUHIOZ-MHTYAFTESA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 AGHMAUIWCUHIOZ-MHTYAFTESA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00104041A EP1127884A1 (en) | 2000-02-26 | 2000-02-26 | Novel malonic acid derivatives, processes for their preparation, their use as inhibitor of factor XA activity and pharmaceutical compositions containing them |
| EP00104041.9 | 2000-02-26 | ||
| PCT/EP2001/001928 WO2001062735A1 (en) | 2000-02-26 | 2001-02-21 | Novel malonic acid derivatives, processes for their preparation, their use as inhibitor of factor xa activity and pharmaceutical compositions containing them |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003524001A JP2003524001A (ja) | 2003-08-12 |
| JP2003524001A5 true JP2003524001A5 (https=) | 2008-04-10 |
Family
ID=8167968
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001562517A Pending JP2003524001A (ja) | 2000-02-26 | 2001-02-21 | 新規マロン酸誘導体、それらの製造法、第Ｘａ因子活性の抑制剤としてのそれらの使用、およびそれらを含有する医薬組成物 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6794365B2 (https=) |
| EP (2) | EP1127884A1 (https=) |
| JP (1) | JP2003524001A (https=) |
| KR (1) | KR20020079892A (https=) |
| CN (1) | CN1406226A (https=) |
| AR (1) | AR027533A1 (https=) |
| AT (1) | ATE314350T1 (https=) |
| AU (1) | AU2001235486A1 (https=) |
| BR (1) | BR0108694A (https=) |
| CA (1) | CA2400871C (https=) |
| CZ (1) | CZ20022862A3 (https=) |
| DE (1) | DE60116272T2 (https=) |
| ES (1) | ES2254370T3 (https=) |
| HK (1) | HK1052696A1 (https=) |
| HU (1) | HUP0300080A3 (https=) |
| IL (1) | IL151459A0 (https=) |
| MX (1) | MXPA02007398A (https=) |
| NO (1) | NO20024040L (https=) |
| NZ (1) | NZ520982A (https=) |
| PL (1) | PL357183A1 (https=) |
| RU (1) | RU2002125671A (https=) |
| WO (1) | WO2001062735A1 (https=) |
| ZA (1) | ZA200206581B (https=) |
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| US20040185015A1 (en) * | 2003-03-17 | 2004-09-23 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Sunscreen cosmetic compositions storage stabilized with malonate salts |
| US20040185073A1 (en) * | 2003-03-17 | 2004-09-23 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Cosmetic compositions containing salts of malonic acid |
| US20040185074A1 (en) * | 2003-03-17 | 2004-09-23 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Odor control in amine salt containing cosmetic compositions |
| US20040202689A1 (en) * | 2003-03-17 | 2004-10-14 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Terpenoid fragrance components stabilized with malonic acid salts |
| US20080194643A1 (en) * | 2005-03-24 | 2008-08-14 | Pfzer Inc | Factor Xa Inhibitor Crystalline Forms |
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| CA2815198A1 (en) | 2010-10-20 | 2012-04-26 | Bioformix Inc. | Synthesis of methylene malonates using rapid recovery in the presence of a heat transfer agent |
| US9828324B2 (en) | 2010-10-20 | 2017-11-28 | Sirrus, Inc. | Methylene beta-diketone monomers, methods for making methylene beta-diketone monomers, polymerizable compositions and products formed therefrom |
| US9279022B1 (en) | 2014-09-08 | 2016-03-08 | Sirrus, Inc. | Solution polymers including one or more 1,1-disubstituted alkene compounds, solution polymerization methods, and polymer compositions |
| US10414839B2 (en) | 2010-10-20 | 2019-09-17 | Sirrus, Inc. | Polymers including a methylene beta-ketoester and products formed therefrom |
| EP2768897B1 (en) | 2011-10-19 | 2019-01-23 | Sirrus, Inc. | Methods for making methylene beta-diketone monomers |
| US9234107B2 (en) | 2012-03-30 | 2016-01-12 | Sirrus, Inc. | Ink coating formulations and polymerizable systems for producing the same |
| CA2869108A1 (en) | 2012-03-30 | 2013-10-03 | Bioformix Inc. | Methods for activating polymerizable compositions, polymerizable systems, and products formed thereby |
| CA2869112A1 (en) | 2012-03-30 | 2013-10-03 | Bioformix Inc. | Composite and laminate articles and polymerizable systems for producing the same |
| WO2013181600A2 (en) | 2012-06-01 | 2013-12-05 | Bioformix Inc. | Optical material and articles formed therefrom |
| WO2014078689A1 (en) | 2012-11-16 | 2014-05-22 | Bioformix Inc. | Plastics bonding systems and methods |
| CN105164797B (zh) | 2012-11-30 | 2019-04-19 | 瑟拉斯公司 | 用于电子应用的复合组合物 |
| EP2943462B1 (en) | 2013-01-11 | 2018-06-27 | Sirrus, Inc. | Method to obtain methylene malonate via bis(hydroxymethyl) malonate pathway |
| US9315597B2 (en) | 2014-09-08 | 2016-04-19 | Sirrus, Inc. | Compositions containing 1,1-disubstituted alkene compounds for preparing polymers having enhanced glass transition temperatures |
| US9416091B1 (en) | 2015-02-04 | 2016-08-16 | Sirrus, Inc. | Catalytic transesterification of ester compounds with groups reactive under transesterification conditions |
| US10501400B2 (en) | 2015-02-04 | 2019-12-10 | Sirrus, Inc. | Heterogeneous catalytic transesterification of ester compounds with groups reactive under transesterification conditions |
| US9334430B1 (en) | 2015-05-29 | 2016-05-10 | Sirrus, Inc. | Encapsulated polymerization initiators, polymerization systems and methods using the same |
| US9217098B1 (en) | 2015-06-01 | 2015-12-22 | Sirrus, Inc. | Electroinitiated polymerization of compositions having a 1,1-disubstituted alkene compound |
| US9518001B1 (en) | 2016-05-13 | 2016-12-13 | Sirrus, Inc. | High purity 1,1-dicarbonyl substituted-1-alkenes and methods for their preparation |
| US10428177B2 (en) | 2016-06-03 | 2019-10-01 | Sirrus, Inc. | Water absorbing or water soluble polymers, intermediate compounds, and methods thereof |
| US10196481B2 (en) | 2016-06-03 | 2019-02-05 | Sirrus, Inc. | Polymer and other compounds functionalized with terminal 1,1-disubstituted alkene monomer(s) and methods thereof |
| US9617377B1 (en) | 2016-06-03 | 2017-04-11 | Sirrus, Inc. | Polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes |
| US9567475B1 (en) | 2016-06-03 | 2017-02-14 | Sirrus, Inc. | Coatings containing polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes |
| CN106501472A (zh) * | 2016-11-29 | 2017-03-15 | 昆明理工大学 | 一种基于抗凝血生化指数评价三七活血作用的方法 |
| CN111018734B (zh) * | 2019-12-13 | 2020-12-22 | 福建海西新药创制有限公司 | 一种盐酸西那卡塞中间体的合成方法 |
| IL316963A (en) * | 2022-05-20 | 2025-01-01 | Radius Health Inc | Process for preparing avalopretide |
| CN115299636B (zh) * | 2022-08-17 | 2025-02-14 | 中国烟草总公司郑州烟草研究院 | 一种卷烟滤嘴用功能吸附丸芯及其制备方法和烟支 |
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| EP0075896B1 (en) * | 1981-09-25 | 1986-02-26 | The Wellcome Foundation Limited | Pharmaceutical amides, and preparation, formulations and use thereof |
| CA2073776A1 (en) * | 1990-11-15 | 1992-05-16 | Joerg Stuerzebecher | Meta-substituted phenyl alanine derivatives |
| JPH07509731A (ja) * | 1993-02-10 | 1995-10-26 | ペンタファルム アクチェンゲゼルシャフト | トロンビン阻害剤としての置換されたフェニルアラニン誘導体のピペラジド |
| SI9520044B (sl) * | 1994-04-26 | 2004-08-31 | Aventis Pharmaceuticals Inc. | Inhibitorji Xa faktorja |
| AU3107795A (en) * | 1994-08-09 | 1996-03-07 | Pentapharm Ag | Inhibitors of the benzamidine type |
| TR199801107T2 (xx) * | 1995-12-20 | 1998-10-21 | Hoechst Marion Roussel Inc. | N-Asetil (L)-4-siyanofenilalanin Ac (L)-phe (4-CN)-OH ve N-Asetil-(L)-p-amidinofenilalanin-sikloheksil-glisin -�-(3-N-metilpiridinyum)-alanin Ac-(L)-pAph-Chg-PalMe (3) -NH2'nin haz�rlanmas� i�in yeni bir i�lem. |
| ID22904A (id) * | 1997-05-02 | 1999-12-16 | Akzo Nobel Nv | Penghambat serin protease |
| TWI222441B (en) * | 1997-11-26 | 2004-10-21 | Dimensional Pharm Inc | Heteroaryl aminoguanidines and alkoxyguanidines and their use as protease inhibitors |
| HU227568B1 (en) | 1997-12-24 | 2011-08-29 | Sanofi Aventis Deutschland | Indole derivatives, as inhibitors os factor xa |
| JP3283485B2 (ja) * | 1998-04-10 | 2002-05-20 | 日本たばこ産業株式会社 | アミジン化合物 |
| JP2002534408A (ja) | 1999-01-02 | 2002-10-15 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | アリールアルカノイル誘導体、その調製のための方法、その使用およびそれらを含有する医薬組成物 |
| KR20010101355A (ko) * | 1999-01-02 | 2001-11-14 | 로버트 흐라이탁, 미쉘 베스트 | 신규한 말론산 유도체, 이의 제조 방법, 이의 용도 및이를 함유하는 약제학적 조성물(인자 ｘａ 활성 억제) |
| EP1016663A1 (en) * | 1999-01-02 | 2000-07-05 | Aventis Pharma Deutschland GmbH | Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor Xa activity) |
-
2000
- 2000-02-26 EP EP00104041A patent/EP1127884A1/en not_active Withdrawn
-
2001
- 2001-02-21 EP EP01907546A patent/EP1265867B1/en not_active Expired - Lifetime
- 2001-02-21 CZ CZ20022862A patent/CZ20022862A3/cs unknown
- 2001-02-21 DE DE60116272T patent/DE60116272T2/de not_active Expired - Lifetime
- 2001-02-21 HK HK03104942.8A patent/HK1052696A1/zh unknown
- 2001-02-21 JP JP2001562517A patent/JP2003524001A/ja active Pending
- 2001-02-21 RU RU2002125671/04A patent/RU2002125671A/ru not_active Application Discontinuation
- 2001-02-21 BR BR0108694-4A patent/BR0108694A/pt not_active Application Discontinuation
- 2001-02-21 MX MXPA02007398A patent/MXPA02007398A/es active IP Right Grant
- 2001-02-21 PL PL01357183A patent/PL357183A1/xx not_active Application Discontinuation
- 2001-02-21 NZ NZ520982A patent/NZ520982A/en unknown
- 2001-02-21 AT AT01907546T patent/ATE314350T1/de not_active IP Right Cessation
- 2001-02-21 WO PCT/EP2001/001928 patent/WO2001062735A1/en not_active Ceased
- 2001-02-21 CA CA2400871A patent/CA2400871C/en not_active Expired - Fee Related
- 2001-02-21 ES ES01907546T patent/ES2254370T3/es not_active Expired - Lifetime
- 2001-02-21 AU AU2001235486A patent/AU2001235486A1/en not_active Abandoned
- 2001-02-21 HU HU0300080A patent/HUP0300080A3/hu unknown
- 2001-02-21 CN CN01805589A patent/CN1406226A/zh active Pending
- 2001-02-21 IL IL15145901A patent/IL151459A0/xx unknown
- 2001-02-21 KR KR1020027011004A patent/KR20020079892A/ko not_active Withdrawn
- 2001-02-22 AR ARP010100806A patent/AR027533A1/es not_active Application Discontinuation
- 2001-02-23 US US09/790,641 patent/US6794365B2/en not_active Expired - Lifetime
-
2002
- 2002-08-16 ZA ZA200206581A patent/ZA200206581B/en unknown
- 2002-08-23 NO NO20024040A patent/NO20024040L/no not_active Application Discontinuation
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