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 |
|---|---|---|---|
| EP00104041.9 | 2000-02-26 | ||
| 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 |
| 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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| US20030224023A1 (en) * | 2002-05-29 | 2003-12-04 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Cosmetic compositions with hydroxy amine salts of malonic acid |
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| 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 |
| 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 |
| KR20070107156A (ko) * | 2005-03-24 | 2007-11-06 | 워너-램버트 캄파니 엘엘씨 | 공지된 피롤리딘 Ｘａ 인자 억제제의 결정질 형태 |
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| 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 |
| SG189933A1 (en) | 2010-10-20 | 2013-06-28 | Bioformix Llc | Synthesis of methylene malonates substantially free of impurities |
| US9249265B1 (en) | 2014-09-08 | 2016-02-02 | Sirrus, Inc. | Emulsion polymers including one or more 1,1-disubstituted alkene compounds, emulsion methods, and polymer compositions |
| US10414839B2 (en) | 2010-10-20 | 2019-09-17 | Sirrus, Inc. | Polymers including a methylene beta-ketoester and products formed therefrom |
| EP3517523A1 (en) | 2011-10-19 | 2019-07-31 | Sirrus, Inc. | Multifunctional monomers and methods for making them |
| EP2831124B1 (en) | 2012-03-30 | 2016-10-05 | Sirrus, Inc. | Composite and laminate articles and polymerizable systems for producing the same |
| JP6188252B2 (ja) | 2012-03-30 | 2017-08-30 | シラス・インコーポレイテッド | 重合性組成物の活性化方法、重合系およびこれにより形成される製品 |
| CA2869115A1 (en) | 2012-03-30 | 2013-10-03 | Bioformix Inc. | Ink and coating formulations and polymerizable systems for producing the same |
| US10047192B2 (en) | 2012-06-01 | 2018-08-14 | Sirrus, Inc. | Optical material and articles formed therefrom |
| WO2014078689A1 (en) | 2012-11-16 | 2014-05-22 | Bioformix Inc. | Plastics bonding systems and methods |
| EP2926368B1 (en) | 2012-11-30 | 2020-04-08 | Sirrus, Inc. | Electronic assembly |
| CN105008321A (zh) | 2013-01-11 | 2015-10-28 | 瑟拉斯公司 | 经过双(羟甲基)丙二酸酯的途径获得亚甲基丙二酸酯的方法 |
| US9416091B1 (en) | 2015-02-04 | 2016-08-16 | Sirrus, Inc. | Catalytic transesterification of ester compounds with groups reactive under transesterification conditions |
| 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 |
| 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 |
| 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 |
| US9567475B1 (en) | 2016-06-03 | 2017-02-14 | Sirrus, Inc. | Coatings containing polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes |
| US9617377B1 (en) | 2016-06-03 | 2017-04-11 | Sirrus, Inc. | Polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes |
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| 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 |
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| 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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| GB2108118B (en) * | 1981-09-25 | 1985-09-11 | Wellcome Found | Pharmaceutical amides and preparation formulations and use thereof |
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| NZ500620A (en) * | 1997-05-02 | 2000-10-27 | Akzo Nobel Nv | Synthetic peptides which inhibit serine proteases, specifically thrombin, factor VIIa tissue factor and factor Xa |
| WO1999026926A1 (en) * | 1997-11-26 | 1999-06-03 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl aminoguanidines and alkoxyguanidines and their use as protease inhibitors |
| DK1042287T3 (da) | 1997-12-24 | 2005-08-15 | Aventis Pharma Gmbh | Indolderivater som inhibitorer af faktor 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 |
| 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) |
| AU2285700A (en) | 1999-01-02 | 2000-07-24 | Aventis Pharma Deutschland Gmbh | Arylalkanoyl derivatives, processes for their preparation, their use and pharmaceutical compositions containing them |
| TR200101903T2 (tr) * | 1999-01-02 | 2001-11-21 | Aventis Pharma Deutschland Gmbh | Yeni malonik asit türevleri, bunların preparasyon işlemleri. |
-
2000
- 2000-02-26 EP EP00104041A patent/EP1127884A1/en not_active Withdrawn
-
2001
- 2001-02-21 BR BR0108694-4A patent/BR0108694A/pt not_active Application Discontinuation
- 2001-02-21 WO PCT/EP2001/001928 patent/WO2001062735A1/en not_active Ceased
- 2001-02-21 JP JP2001562517A patent/JP2003524001A/ja active Pending
- 2001-02-21 HK HK03104942.8A patent/HK1052696A1/zh unknown
- 2001-02-21 EP EP01907546A patent/EP1265867B1/en not_active Expired - Lifetime
- 2001-02-21 MX MXPA02007398A patent/MXPA02007398A/es active IP Right Grant
- 2001-02-21 CZ CZ20022862A patent/CZ20022862A3/cs unknown
- 2001-02-21 KR KR1020027011004A patent/KR20020079892A/ko not_active Withdrawn
- 2001-02-21 CA CA2400871A patent/CA2400871C/en not_active Expired - Fee Related
- 2001-02-21 AU AU2001235486A patent/AU2001235486A1/en not_active Abandoned
- 2001-02-21 DE DE60116272T patent/DE60116272T2/de not_active Expired - Lifetime
- 2001-02-21 ES ES01907546T patent/ES2254370T3/es not_active Expired - Lifetime
- 2001-02-21 NZ NZ520982A patent/NZ520982A/en unknown
- 2001-02-21 RU RU2002125671/04A patent/RU2002125671A/ru not_active Application Discontinuation
- 2001-02-21 CN CN01805589A patent/CN1406226A/zh active Pending
- 2001-02-21 PL PL01357183A patent/PL357183A1/xx not_active Application Discontinuation
- 2001-02-21 AT AT01907546T patent/ATE314350T1/de not_active IP Right Cessation
- 2001-02-21 IL IL15145901A patent/IL151459A0/xx unknown
- 2001-02-21 HU HU0300080A patent/HUP0300080A3/hu unknown
- 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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