CA2674843A1 - Factor xa inhibitors - Google Patents
Factor xa inhibitors Download PDFInfo
- Publication number
- CA2674843A1 CA2674843A1 CA002674843A CA2674843A CA2674843A1 CA 2674843 A1 CA2674843 A1 CA 2674843A1 CA 002674843 A CA002674843 A CA 002674843A CA 2674843 A CA2674843 A CA 2674843A CA 2674843 A1 CA2674843 A1 CA 2674843A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- carboxamide
- chloro
- thiophene
- phenyl
- 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.)
- Abandoned
Links
- 229940123583 Factor Xa inhibitor Drugs 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 220
- 238000000034 method Methods 0.000 claims abstract description 74
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 17
- 239000000651 prodrug Substances 0.000 claims abstract description 13
- 229940002612 prodrug Drugs 0.000 claims abstract description 13
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 210000004369 blood Anatomy 0.000 claims abstract description 6
- 239000008280 blood Substances 0.000 claims abstract description 6
- 230000015271 coagulation Effects 0.000 claims abstract description 5
- 238000005345 coagulation Methods 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 166
- 239000000203 mixture Substances 0.000 claims description 162
- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 claims description 116
- -1 nitro, hydroxy Chemical group 0.000 claims description 115
- 125000000217 alkyl group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- RATVVOKWZYXAKP-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-oxopiperazin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(CNCC2)=O)N=N1 RATVVOKWZYXAKP-UHFFFAOYSA-N 0.000 claims description 5
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 5
- 206010047249 Venous thrombosis Diseases 0.000 claims description 5
- 239000003146 anticoagulant agent Substances 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- SNFVWEAZGAJSJP-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2,4-dimethoxypyrimidin-5-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound COC1=NC(OC)=NC=C1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 SNFVWEAZGAJSJP-UHFFFAOYSA-N 0.000 claims description 4
- GFWYXAZYVZGBIW-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-oxopyridin-1-yl)-2-(4-propan-2-ylpiperazin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound C1CN(C(C)C)CCN1C1=CC(N2C(C=CC=C2)=O)=CC=C1N1N=NC(CNC(=O)C=2SC(Cl)=CC=2)=C1 GFWYXAZYVZGBIW-UHFFFAOYSA-N 0.000 claims description 4
- OOBGVAVGWJSNDQ-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-oxopyridin-1-yl)-2-piperazin-1-ylphenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C(=CC(=CC=2)N2C(C=CC=C2)=O)N2CCNCC2)N=N1 OOBGVAVGWJSNDQ-UHFFFAOYSA-N 0.000 claims description 4
- KIWAJECUKDAMTL-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(3-hydroxy-2-oxopyridin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound O=C1C(O)=CC=CN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 KIWAJECUKDAMTL-UHFFFAOYSA-N 0.000 claims description 4
- AGPUPLOVSPHBRW-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(5-hydroxy-2-oxopyridin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound C1=C(O)C=CC(=O)N1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 AGPUPLOVSPHBRW-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 230000001732 thrombotic effect Effects 0.000 claims description 4
- OPZZSJCZTIEEPS-UHFFFAOYSA-N 4-[4-[4-[[(5-chlorothiophene-2-carbonyl)amino]methyl]triazol-1-yl]phenyl]-3-oxopiperazine-1-carboxamide Chemical compound O=C1CN(C(=O)N)CCN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 OPZZSJCZTIEEPS-UHFFFAOYSA-N 0.000 claims description 3
- JBMQUFWOIFKATH-UHFFFAOYSA-N 4-chloro-n-[[1-[4-(2-oxopyridin-1-yl)phenyl]imidazol-4-yl]methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(C=CC=C2)=O)C=N1 JBMQUFWOIFKATH-UHFFFAOYSA-N 0.000 claims description 3
- WVDGGELBAQPQRW-UHFFFAOYSA-N 5-chloro-N-[[1-[4-[3-[2-(2-methyl-2-propan-2-ylhydrazinyl)ethoxy]-2-oxopyridin-1-yl]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound ClC1=CC=C(S1)C(=O)NCC=1N=NN(C1)C1=CC=C(C=C1)N1C(C(=CC=C1)OCCNN(C(C)C)C)=O WVDGGELBAQPQRW-UHFFFAOYSA-N 0.000 claims description 3
- RPMKFVQSNMNQHH-UHFFFAOYSA-N 5-chloro-n-[[1-(4-iodophenyl)imidazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(I)=CC=2)C=N1 RPMKFVQSNMNQHH-UHFFFAOYSA-N 0.000 claims description 3
- RZDMJAVPTRNTMT-UHFFFAOYSA-N 5-chloro-n-[[1-[2-(4-ethylpiperazin-1-yl)-4-(2-oxopyridin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound C1CN(CC)CCN1C1=CC(N2C(C=CC=C2)=O)=CC=C1N1N=NC(CNC(=O)C=2SC(Cl)=CC=2)=C1 RZDMJAVPTRNTMT-UHFFFAOYSA-N 0.000 claims description 3
- YUMHMIRMMVSWBC-UHFFFAOYSA-N 5-chloro-n-[[1-[2-fluoro-4-(2-oxo-1,3-diazinan-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound FC1=CC(N2C(NCCC2)=O)=CC=C1N(N=N1)C=C1CNC(=O)C1=CC=C(Cl)S1 YUMHMIRMMVSWBC-UHFFFAOYSA-N 0.000 claims description 3
- UTONCGBWJKLASU-UHFFFAOYSA-N 5-chloro-n-[[1-[2-fluoro-4-(2-oxopiperidin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound FC1=CC(N2C(CCCC2)=O)=CC=C1N(N=N1)C=C1CNC(=O)C1=CC=C(Cl)S1 UTONCGBWJKLASU-UHFFFAOYSA-N 0.000 claims description 3
- UXDFFJQWRALQBE-UHFFFAOYSA-N 5-chloro-n-[[1-[2-fluoro-4-(2-oxopyrazin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound FC1=CC(N2C(C=NC=C2)=O)=CC=C1N(N=N1)C=C1CNC(=O)C1=CC=C(Cl)S1 UXDFFJQWRALQBE-UHFFFAOYSA-N 0.000 claims description 3
- BWOIKMAHNJFFHD-UHFFFAOYSA-N 5-chloro-n-[[1-[2-fluoro-4-(2-oxopyrimidin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound FC1=CC(N2C(N=CC=C2)=O)=CC=C1N(N=N1)C=C1CNC(=O)C1=CC=C(Cl)S1 BWOIKMAHNJFFHD-UHFFFAOYSA-N 0.000 claims description 3
- SMHXSIQGMQVLFQ-UHFFFAOYSA-N 5-chloro-n-[[1-[2-fluoro-4-(3-methyl-2-oxo-1,3-diazinan-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound O=C1N(C)CCCN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C(F)=C1 SMHXSIQGMQVLFQ-UHFFFAOYSA-N 0.000 claims description 3
- YTEKDQYUNGLOSP-UHFFFAOYSA-N 5-chloro-n-[[1-[3-fluoro-4-(2-oxopyridin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound FC1=CC(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)=CC=C1N1C=CC=CC1=O YTEKDQYUNGLOSP-UHFFFAOYSA-N 0.000 claims description 3
- LXLCGGRDUVNIBC-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(1-methyl-6-oxopyridazin-3-yl)phenyl]imidazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound C1=CC(=O)N(C)N=C1C1=CC=C(N2C=C(CNC(=O)C=3SC(Cl)=CC=3)N=C2)C=C1 LXLCGGRDUVNIBC-UHFFFAOYSA-N 0.000 claims description 3
- VOHLLTDPNSKGFF-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(1-methyl-6-oxopyridazin-3-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound C1=CC(=O)N(C)N=C1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 VOHLLTDPNSKGFF-UHFFFAOYSA-N 0.000 claims description 3
- OLWRNSOZNIWVCS-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2,3-dioxo-1h-pyrazin-4-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound O=C1C(O)=NC=CN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 OLWRNSOZNIWVCS-UHFFFAOYSA-N 0.000 claims description 3
- FEPGEIOLKWXESP-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2,4-dioxopyrimidin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(NC(=O)C=C2)=O)N=N1 FEPGEIOLKWXESP-UHFFFAOYSA-N 0.000 claims description 3
- ZRJOAXZQNPYXNB-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2,5-dihydropyrrole-1-carbonyl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)C(=O)N2CC=CC2)N=N1 ZRJOAXZQNPYXNB-UHFFFAOYSA-N 0.000 claims description 3
- CPFRKRRZEKLLBO-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-hydroxyphenyl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound OC1=CC=CC=C1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 CPFRKRRZEKLLBO-UHFFFAOYSA-N 0.000 claims description 3
- SCBSYDLJTODSKA-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-methoxyphenyl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound COC1=CC=CC=C1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 SCBSYDLJTODSKA-UHFFFAOYSA-N 0.000 claims description 3
- XKITYJYGSAIICA-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-methoxypyridin-3-yl)phenyl]imidazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound COC1=NC=CC=C1C1=CC=C(N2C=C(CNC(=O)C=3SC(Cl)=CC=3)N=C2)C=C1 XKITYJYGSAIICA-UHFFFAOYSA-N 0.000 claims description 3
- RNXYUXZVUHHASO-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-oxo-1h-pyridin-3-yl)phenyl]imidazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)C=2C(NC=CC=2)=O)C=N1 RNXYUXZVUHHASO-UHFFFAOYSA-N 0.000 claims description 3
- DXGLTXOTVXRFRR-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-oxopyrazin-1-yl)phenyl]pyrazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(C=NC=C2)=O)N=C1 DXGLTXOTVXRFRR-UHFFFAOYSA-N 0.000 claims description 3
- SYSMSWCIQCHIEM-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-oxopyridin-1-yl)phenyl]pyrazol-3-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=NN(C=2C=CC(=CC=2)N2C(C=CC=C2)=O)C=C1 SYSMSWCIQCHIEM-UHFFFAOYSA-N 0.000 claims description 3
- PYOMIURPKNDCKB-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-oxopyridin-1-yl)phenyl]pyrazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(C=CC=C2)=O)N=C1 PYOMIURPKNDCKB-UHFFFAOYSA-N 0.000 claims description 3
- GKQLTXHQRWOOSY-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-oxopyridin-1-yl)phenyl]pyrrol-3-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(C=CC=C2)=O)C=C1 GKQLTXHQRWOOSY-UHFFFAOYSA-N 0.000 claims description 3
- VGQLDWPXYKIISM-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(2-oxopyrimidin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(N=CC=C2)=O)N=N1 VGQLDWPXYKIISM-UHFFFAOYSA-N 0.000 claims description 3
- SBHNVOHSTIDXEY-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(3-methyl-2,4-dioxopyrimidin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound O=C1N(C)C(=O)C=CN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 SBHNVOHSTIDXEY-UHFFFAOYSA-N 0.000 claims description 3
- BIVRWARUUGATHG-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(4-methyl-1,4-diazepan-1-yl)phenyl]pyrazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound C1CN(C)CCCN1C1=CC=C(N2N=CC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 BIVRWARUUGATHG-UHFFFAOYSA-N 0.000 claims description 3
- MVQHWEHSUWMMBG-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(4-methyl-1,4-diazepan-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound C1CN(C)CCCN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 MVQHWEHSUWMMBG-UHFFFAOYSA-N 0.000 claims description 3
- ZNVAIBDQWDKKMS-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(4-methyl-2-oxopiperazin-1-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound O=C1CN(C)CCN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 ZNVAIBDQWDKKMS-UHFFFAOYSA-N 0.000 claims description 3
- UKSQOQISMPHDNF-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(6-chloropyridin-3-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)C=2C=NC(Cl)=CC=2)N=N1 UKSQOQISMPHDNF-UHFFFAOYSA-N 0.000 claims description 3
- KJJYGWAGSXMOCQ-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(6-oxo-1h-pyridazin-3-yl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)C2=NNC(=O)C=C2)N=N1 KJJYGWAGSXMOCQ-UHFFFAOYSA-N 0.000 claims description 3
- HNGLSEOYSMTFPC-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(methylamino)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound C1=CC(NC)=CC=C1N1N=NC(CNC(=O)C=2SC(Cl)=CC=2)=C1 HNGLSEOYSMTFPC-UHFFFAOYSA-N 0.000 claims description 3
- BKFDAFZIOYPEMP-UHFFFAOYSA-N 5-chloro-n-[[1-[4-(pyrrolidine-1-carbonyl)phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)C(=O)N2CCCC2)N=N1 BKFDAFZIOYPEMP-UHFFFAOYSA-N 0.000 claims description 3
- GXQKVIJVPKRVNL-UHFFFAOYSA-N 5-chloro-n-[[1-[4-[(2-methoxyacetyl)-methylamino]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound C1=CC(N(C)C(=O)COC)=CC=C1N1N=NC(CNC(=O)C=2SC(Cl)=CC=2)=C1 GXQKVIJVPKRVNL-UHFFFAOYSA-N 0.000 claims description 3
- ZRMFIQSCNUQWLS-UHFFFAOYSA-N 5-chloro-n-[[1-[4-[2-(trifluoromethoxy)phenyl]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound FC(F)(F)OC1=CC=CC=C1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 ZRMFIQSCNUQWLS-UHFFFAOYSA-N 0.000 claims description 3
- FZHQZYILNZHRCM-UHFFFAOYSA-N 5-chloro-n-[[1-[4-[2-oxo-3-(2-piperidin-1-ylethoxy)pyridin-1-yl]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(C(OCCN3CCCCC3)=CC=C2)=O)N=N1 FZHQZYILNZHRCM-UHFFFAOYSA-N 0.000 claims description 3
- SMCZJWLTTQNLJA-UHFFFAOYSA-N 5-chloro-n-[[1-[4-[2-oxo-3-(3-piperidin-1-ylpropoxy)pyridin-1-yl]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(C(OCCCN3CCCCC3)=CC=C2)=O)N=N1 SMCZJWLTTQNLJA-UHFFFAOYSA-N 0.000 claims description 3
- VFELFOQINSNXLL-UHFFFAOYSA-N 5-chloro-n-[[1-[4-[3-(2-hydroxyethoxy)-2-oxopyridin-1-yl]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound O=C1C(OCCO)=CC=CN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 VFELFOQINSNXLL-UHFFFAOYSA-N 0.000 claims description 3
- BRLSGRUWHGRACW-UHFFFAOYSA-N 5-chloro-n-[[1-[4-[3-(2-imidazol-1-ylethoxy)-2-oxopyridin-1-yl]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(C(OCCN3C=NC=C3)=CC=C2)=O)N=N1 BRLSGRUWHGRACW-UHFFFAOYSA-N 0.000 claims description 3
- LOZXELVWDWEWTM-UHFFFAOYSA-N 5-chloro-n-[[1-[4-[3-(2-methoxyethoxy)-2-oxopyridin-1-yl]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound O=C1C(OCCOC)=CC=CN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 LOZXELVWDWEWTM-UHFFFAOYSA-N 0.000 claims description 3
- ASZXNLMHOAGOJR-UHFFFAOYSA-N 5-chloro-n-[[1-[4-[3-(2-methylsulfanylethoxy)-2-oxopyridin-1-yl]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound O=C1C(OCCSC)=CC=CN1C1=CC=C(N2N=NC(CNC(=O)C=3SC(Cl)=CC=3)=C2)C=C1 ASZXNLMHOAGOJR-UHFFFAOYSA-N 0.000 claims description 3
- MQNLYZJLBWRVJB-UHFFFAOYSA-N 5-chloro-n-[[1-[4-[3-(2-morpholin-4-ylethoxy)-2-oxopyridin-1-yl]phenyl]triazol-4-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NCC1=CN(C=2C=CC(=CC=2)N2C(C(OCCN3CCOCC3)=CC=C2)=O)N=N1 MQNLYZJLBWRVJB-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- 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
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/620,615 US7696352B2 (en) | 2004-06-18 | 2007-01-05 | Factor Xa inhibitors |
| US11/620,615 | 2007-01-05 | ||
| PCT/US2008/050244 WO2008086188A2 (en) | 2007-01-05 | 2008-01-04 | Thiophene carboxamides as factor xa inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2674843A1 true CA2674843A1 (en) | 2008-07-17 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002674843A Abandoned CA2674843A1 (en) | 2007-01-05 | 2008-01-04 | Factor xa inhibitors |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US7696352B2 (enExample) |
| EP (1) | EP2114928A2 (enExample) |
| JP (1) | JP2010515689A (enExample) |
| AU (1) | AU2008205143A1 (enExample) |
| CA (1) | CA2674843A1 (enExample) |
| WO (1) | WO2008086188A2 (enExample) |
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| AU2001245353A1 (en) | 2000-02-29 | 2001-09-12 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor xa |
| BRPI0512273A (pt) * | 2004-06-18 | 2008-02-19 | Millennium Pharm Inc | inibidores do fator xa |
| US7696352B2 (en) * | 2004-06-18 | 2010-04-13 | Millennium Pharmaceuticals, Inc. | Factor Xa inhibitors |
| PT1928454E (pt) | 2005-05-10 | 2014-12-04 | Intermune Inc | Derivativos da piridona para modulação do sistema de proteína quinase ativada pelo stress |
| WO2007112367A2 (en) * | 2006-03-27 | 2007-10-04 | Portola Pharmaceuticals, Inc. | Potassium channel modulators and platelet procoagulant activity |
| TW200813017A (en) | 2006-05-05 | 2008-03-16 | Millennium Pharm Inc | Factor XA inhibitors |
| ATE544749T1 (de) | 2006-11-02 | 2012-02-15 | Millennium Pharm Inc | Verfahren zur synthetisierung pharmazeutischer salze aus einem faktor-xa-hemmer |
| JP2010515691A (ja) * | 2007-01-05 | 2010-05-13 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | 第Ｘａ因子阻害剤 |
| MX2009010953A (es) | 2007-04-13 | 2009-10-29 | Millenium Pharmaceuticals Inc | Terapia anticoagulante en combinacion, con un compuesto que actua como un inhibidor del factor xa. |
| MX2009011755A (es) * | 2007-05-02 | 2010-02-12 | Portola Pharm Inc | Terapia de combinacion con un compuesto que actua como un inhibidor del receptor adp de plaquetas. |
| WO2009063029A2 (en) * | 2007-11-16 | 2009-05-22 | Boehringer Ingelheim International Gmbh | Substituted amides, manufacturing and use thereof as medicaments |
| US8278340B2 (en) | 2007-11-27 | 2012-10-02 | North Carolina State University | Inhibition of biofilms in plants with imidazole derivatives |
| EP2296653B1 (en) | 2008-06-03 | 2016-01-27 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| CA2728769A1 (en) * | 2008-07-04 | 2010-01-07 | Bruno Villoutreix | Nitrogen heterocycle derivatives as proteasome modulators |
| US20110294668A1 (en) | 2008-12-08 | 2011-12-01 | North Carolina State University | Inhibition and dispersion of biofilms in plants with imidazole-triazole derivatives |
| CN102482228A (zh) | 2009-07-17 | 2012-05-30 | 盐野义制药株式会社 | 含有内酰胺或苯磺酰胺化合物的药物 |
| ES2610145T3 (es) | 2009-12-17 | 2017-04-26 | Millennium Pharmaceuticals, Inc. | Procedimientos de síntesis de inhibidores del factor Xa |
| CN102762550B (zh) * | 2009-12-17 | 2015-04-01 | 米伦纽姆医药公司 | Xa因子抑制剂的盐和结晶形式 |
| WO2011075602A1 (en) | 2009-12-17 | 2011-06-23 | Millennium Pharmaceuticals, Inc. | Methods of preparing factor xa inhibitors and salts thereof |
| US20130096160A1 (en) * | 2010-04-14 | 2013-04-18 | Secretary, Department Of Health And Human Services | Arylthiazolyl piperidines and related compounds as modulators of survival motor neuron (smn) protein production |
| TW201221128A (en) | 2010-09-01 | 2012-06-01 | Portola Pharm Inc | Crystalline forms of a factor Xa inhibitor |
| TW201240664A (en) | 2010-09-01 | 2012-10-16 | Portola Pharm Inc | Methods and formulations of treating thrombosis with betrixaban and a P-glycoprotein inhibitor |
| CN102219753B (zh) * | 2011-04-21 | 2012-10-31 | 山东大学 | 一种三氮唑类化合物及其制备方法与应用 |
| US20150224091A1 (en) | 2011-08-31 | 2015-08-13 | Portola Pharmaceuticals, Inc. | Prevention and treatment of thrombosis in medically ill patients |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| NZ630205A (en) * | 2013-04-30 | 2017-03-31 | Glaxosmithkline Intellectual Property (No 2) Ltd | Enhancer of zeste homolog 2 inhibitors |
| WO2015153683A1 (en) | 2014-04-02 | 2015-10-08 | Intermune, Inc. | Anti-fibrotic pyridinones |
| MX382526B (es) | 2015-10-23 | 2025-03-13 | Array Biopharma Inc | Compuestos de 2-piridazin-3(2h)-ona 2-aril sustituidas y 2-heteroaril sustituidas como inhibidores de las tirosina quinasas fgfr |
| BR112019008372B1 (pt) * | 2016-12-29 | 2021-11-09 | Dow Agrosciences Llc | Processo para preparação de compostos pesticidas |
| JP2022515198A (ja) | 2018-12-19 | 2022-02-17 | アレイ バイオファーマ インコーポレイテッド | ＦＧＦＲチロシンキナーゼの阻害剤としての置換ピラゾロ［１，５－ａ］ピリジン化合物 |
| US12351571B2 (en) | 2018-12-19 | 2025-07-08 | Array Biopharma Inc. | Substituted quinoxaline compounds as inhibitors of FGFR tyrosine kinases |
| NL2024731B1 (en) | 2020-01-22 | 2021-09-09 | Sonova Ag | Acoustic device with deformable shape as valve |
| NL2024842B1 (en) | 2020-02-05 | 2021-09-13 | Sonova Ag | Acoustic device with sma microspring switch |
| WO2022081573A1 (en) * | 2020-10-12 | 2022-04-21 | University Of Tennessee Research Foundation | Transient receptor potential canonical 3 inhibitors and methods of use thereof |
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| US6514977B1 (en) | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| GB9725244D0 (en) | 1997-11-29 | 1998-01-28 | Zeneca Ltd | Chemical compounds |
| US6844367B1 (en) * | 1999-09-17 | 2005-01-18 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| WO2001021160A2 (en) | 1999-09-23 | 2001-03-29 | Axxima Pharmaceuticals Aktiengesellschaft | Carboxymide and aniline derivatives as selective inhibitors of pathogens |
| DE19962924A1 (de) | 1999-12-24 | 2001-07-05 | Bayer Ag | Substituierte Oxazolidinone und ihre Verwendung |
| AU2001245353A1 (en) * | 2000-02-29 | 2001-09-12 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor xa |
| DE10027151A1 (de) | 2000-05-31 | 2001-12-06 | Bayer Ag | Herbizide Mittel auf Basis von substituierten Carbonsäureamiden |
| WO2002000651A2 (en) | 2000-06-27 | 2002-01-03 | Bristol-Myers Squibb Pharma Company | Factor xa inhibitors |
| US7312235B2 (en) * | 2001-03-30 | 2007-12-25 | Millennium Pharmaceuticals, Inc. | Benzamide inhibitors of factor Xa |
| ES2180456B1 (es) | 2001-07-20 | 2004-05-01 | Laboratorios S.A.L.V.A.T., S.A. | Isoxazoles sustituidos y su utilizacion como antibioticos. |
| US6914058B2 (en) | 2002-01-18 | 2005-07-05 | Dr. Reddy's Laboratories, Limited | Antibacterial compounds: process for their preparation and pharmaceutical compositions containing them |
| US20050171358A1 (en) | 2002-03-07 | 2005-08-04 | Noriko Shimozono | Substituted isoxazole alkylamine derivative and agri-and horticultural fungicide |
| JP3090812U (ja) * | 2002-06-18 | 2002-12-26 | アルプス電気株式会社 | 高周波モジュール |
| WO2004101531A1 (en) | 2003-04-29 | 2004-11-25 | Dr. Reddy's Laboratories Ltd. | Antiinfective 1,2,3-triazole derivatives, process for their preparation and pharmaceutical compositions containing them |
| DE10322469A1 (de) | 2003-05-19 | 2004-12-16 | Bayer Healthcare Ag | Heterocyclische Verbindungen |
| WO2004106329A2 (en) | 2003-06-03 | 2004-12-09 | Dr. Reddy's Laboratories Ltd. | Novel antiinfective compounds and their pharmaceutical compositions |
| US7199149B2 (en) | 2003-10-01 | 2007-04-03 | Bristol Myers Squibb Company | Monocyclic and bicyclic lactams as factor Xa inhibitors |
| EP1678161B1 (en) * | 2003-10-09 | 2009-12-30 | Millennium Pharmaceuticals, Inc. | Thioether-substituted benzamides as inhibitors of factor xa |
| WO2005035528A2 (en) | 2003-10-14 | 2005-04-21 | Dr. Reddy's Laboratories Ltd. | Triazole derivatives as antibacterial agents |
| WO2005082892A2 (en) | 2004-02-17 | 2005-09-09 | Dr. Reddy's Laboratories Ltd. | Triazole compounds as antibacterial agents and pharmaceutical compositions containing them |
| BRPI0512273A (pt) * | 2004-06-18 | 2008-02-19 | Millennium Pharm Inc | inibidores do fator xa |
| US7696352B2 (en) * | 2004-06-18 | 2010-04-13 | Millennium Pharmaceuticals, Inc. | Factor Xa inhibitors |
| AR057976A1 (es) | 2005-08-29 | 2008-01-09 | Boehringer Ingelheim Int | Biarilos sustituidos y su uso como medicamentos. |
| CN102336702B (zh) * | 2005-11-08 | 2015-02-11 | 米伦纽姆医药公司 | Xa因子抑制剂n-(5-氯-2-吡啶基)-2-[[4-[(二甲氨基)亚氨基甲基]苯甲酰基]氨基]-5-甲氧基-苯甲酰胺的医药盐和多晶型 |
| WO2007112367A2 (en) * | 2006-03-27 | 2007-10-04 | Portola Pharmaceuticals, Inc. | Potassium channel modulators and platelet procoagulant activity |
| TW200813017A (en) | 2006-05-05 | 2008-03-16 | Millennium Pharm Inc | Factor XA inhibitors |
| US20080051578A1 (en) * | 2006-08-24 | 2008-02-28 | Georg Dahmann | Substituted biaryls, process for their manufacture and use thereof as medicaments |
| ATE544749T1 (de) * | 2006-11-02 | 2012-02-15 | Millennium Pharm Inc | Verfahren zur synthetisierung pharmazeutischer salze aus einem faktor-xa-hemmer |
| WO2008073670A2 (en) * | 2006-12-08 | 2008-06-19 | Millennium Pharmaceuticals, Inc. | Unit dose formulations and methods of treating thrombosis with an oral factor xa inhibitor |
| JP2010515691A (ja) * | 2007-01-05 | 2010-05-13 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | 第Ｘａ因子阻害剤 |
| US20080241233A1 (en) * | 2007-03-28 | 2008-10-02 | Portola Pharmaceuticals, Inc. | Targeted delivery and expression of procoagulant hemostatic activity |
| MX2009010953A (es) * | 2007-04-13 | 2009-10-29 | Millenium Pharmaceuticals Inc | Terapia anticoagulante en combinacion, con un compuesto que actua como un inhibidor del factor xa. |
| MX2009011755A (es) * | 2007-05-02 | 2010-02-12 | Portola Pharm Inc | Terapia de combinacion con un compuesto que actua como un inhibidor del receptor adp de plaquetas. |
| KR102069498B1 (ko) * | 2007-09-28 | 2020-01-23 | 포톨라 파마슈티컬스, 인코포레이티드 | 인자 Ｘａ 저해제에 대한 안티도트 및 그것을 사용하는 방법 |
| MX2011004907A (es) * | 2008-11-14 | 2011-07-29 | Portola Pharm Inc | Antidotos para inhibidores del factor xa y metodos para el uso de los mismos en combinacion con agentes de coagulacion de sangre. |
-
2007
- 2007-01-05 US US11/620,615 patent/US7696352B2/en not_active Expired - Fee Related
-
2008
- 2008-01-04 WO PCT/US2008/050244 patent/WO2008086188A2/en not_active Ceased
- 2008-01-04 JP JP2009544989A patent/JP2010515689A/ja not_active Withdrawn
- 2008-01-04 AU AU2008205143A patent/AU2008205143A1/en not_active Abandoned
- 2008-01-04 CA CA002674843A patent/CA2674843A1/en not_active Abandoned
- 2008-01-04 EP EP08705691A patent/EP2114928A2/en not_active Withdrawn
-
2010
- 2010-01-29 US US12/697,135 patent/US20100234352A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20070185092A1 (en) | 2007-08-09 |
| WO2008086188A3 (en) | 2008-10-09 |
| US20100234352A1 (en) | 2010-09-16 |
| EP2114928A2 (en) | 2009-11-11 |
| JP2010515689A (ja) | 2010-05-13 |
| AU2008205143A1 (en) | 2008-07-17 |
| WO2008086188A2 (en) | 2008-07-17 |
| US7696352B2 (en) | 2010-04-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20130104 |