DE19755268A1 - Benzamidinderivate - Google Patents
BenzamidinderivateInfo
- Publication number
- DE19755268A1 DE19755268A1 DE19755268A DE19755268A DE19755268A1 DE 19755268 A1 DE19755268 A1 DE 19755268A1 DE 19755268 A DE19755268 A DE 19755268A DE 19755268 A DE19755268 A DE 19755268A DE 19755268 A1 DE19755268 A1 DE 19755268A1
- Authority
- DE
- Germany
- Prior art keywords
- methyl
- oxazolidin
- ylmethyl
- phenyl
- formula
- 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.)
- Withdrawn
Links
- 150000003937 benzamidines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 114
- 108010074860 Factor Xa Proteins 0.000 claims abstract description 11
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 4
- 239000003112 inhibitor Substances 0.000 claims abstract 2
- -1 Hal F Chemical group 0.000 claims description 245
- 229910052757 nitrogen Inorganic materials 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 229910052794 bromium Inorganic materials 0.000 claims description 14
- 239000000460 chlorine Chemical group 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 229910052740 iodine Inorganic materials 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 8
- 208000007536 Thrombosis Diseases 0.000 claims description 7
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 206010002383 Angina Pectoris Diseases 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 206010022562 Intermittent claudication Diseases 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 4
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 4
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 208000010125 myocardial infarction Diseases 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 238000002399 angioplasty Methods 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 150000004866 oxadiazoles Chemical class 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- YZEPMQXUPCJOCY-UHFFFAOYSA-N 3-[[3-(4-carbamimidoylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methoxy]benzenecarboximidamide Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)OC(COC=2C=C(C=CC=2)C(N)=N)C1 YZEPMQXUPCJOCY-UHFFFAOYSA-N 0.000 claims description 2
- QROCYRVGCHDDLR-UHFFFAOYSA-N 4-[[2-hydroxy-3-[(4-propan-2-ylphenyl)sulfonylmethylamino]propyl]amino]benzenecarboximidamide Chemical compound C(C)(C)C1=CC=C(C=C1)S(=O)(=O)CNCC(CNC1=CC=C(C(=N)N)C=C1)O QROCYRVGCHDDLR-UHFFFAOYSA-N 0.000 claims description 2
- CWJXCAVJQCBDSD-UHFFFAOYSA-N 4-[[3-[4-(2,6-dichloro-4-methoxyphenyl)sulfonylpiperazin-1-yl]-2-hydroxypropyl]amino]benzenecarboximidamide Chemical compound ClC1=CC(OC)=CC(Cl)=C1S(=O)(=O)N1CCN(CC(O)CNC=2C=CC(=CC=2)C(N)=N)CC1 CWJXCAVJQCBDSD-UHFFFAOYSA-N 0.000 claims description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- BTLRKVDLMIGGOS-UHFFFAOYSA-N 4-[[2-hydroxy-3-[4-(2-naphthalen-1-ylphenyl)sulfonylpiperazin-1-yl]propyl]amino]benzenecarboximidamide Chemical compound C1=CC(C(=N)N)=CC=C1NCC(O)CN1CCN(S(=O)(=O)C=2C(=CC=CC=2)C=2C3=CC=CC=C3C=CC=2)CC1 BTLRKVDLMIGGOS-UHFFFAOYSA-N 0.000 claims 1
- 206010061216 Infarction Diseases 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 230000007574 infarction Effects 0.000 claims 1
- 210000004165 myocardium Anatomy 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 208000001435 Thromboembolism Diseases 0.000 abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 238000010265 fast atom bombardment Methods 0.000 description 166
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 115
- 229940022663 acetate Drugs 0.000 description 115
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 238000005984 hydrogenation reaction Methods 0.000 description 17
- 239000004480 active ingredient Substances 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- 239000012442 inert solvent Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- WTDHULULXKLSOZ-UHFFFAOYSA-N hydroxylamine hydrochloride Substances Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 7
- HJJPIFMUUQYUON-UHFFFAOYSA-N methyl [3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methanesulfonate Chemical compound O=C1OC(CS(=O)(=O)OC)CN1C1=CC=C(C=2N=C(C)ON=2)C=C1 HJJPIFMUUQYUON-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 238000010626 work up procedure Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 229960004756 ethanol Drugs 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- WCYJQVALWQMJGE-UHFFFAOYSA-M hydroxylammonium chloride Chemical compound [Cl-].O[NH3+] WCYJQVALWQMJGE-UHFFFAOYSA-M 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
- WHJAQKAAIOHCGN-UHFFFAOYSA-N 2,4,6-trichlorobenzenesulfonyl chloride Chemical compound ClC1=CC(Cl)=C(S(Cl)(=O)=O)C(Cl)=C1 WHJAQKAAIOHCGN-UHFFFAOYSA-N 0.000 description 3
- CDFCJDHGBCGHMG-UHFFFAOYSA-N 3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-5-[[4-(2,4,6-trichlorophenyl)sulfonylpiperazin-1-yl]methyl]-1,3-oxazolidin-2-one Chemical compound O1C(C)=NC(C=2C=CC(=CC=2)N2C(OC(CN3CCN(CC3)S(=O)(=O)C=3C(=CC(Cl)=CC=3Cl)Cl)C2)=O)=N1 CDFCJDHGBCGHMG-UHFFFAOYSA-N 0.000 description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- LEFGAGRZHLNPLS-UHFFFAOYSA-N 4-propylbenzenesulfonyl chloride Chemical compound CCCC1=CC=C(S(Cl)(=O)=O)C=C1 LEFGAGRZHLNPLS-UHFFFAOYSA-N 0.000 description 3
- ANPIUIKFTZXVFA-UHFFFAOYSA-N 5-(aminomethyl)-3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-1,3-oxazolidin-2-one Chemical compound O1C(C)=NC(C=2C=CC(=CC=2)N2C(OC(CN)C2)=O)=N1 ANPIUIKFTZXVFA-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 108090000190 Thrombin Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 230000002785 anti-thrombosis Effects 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940113088 dimethylacetamide Drugs 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 229960004072 thrombin Drugs 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- LDFPQCYQWOWKCY-UHFFFAOYSA-N 1-[4-(2,6-dichloro-4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)anilino]propan-2-ol Chemical compound ClC1=CC(OC)=CC(Cl)=C1S(=O)(=O)N1CCN(CC(O)CNC=2C=CC(=CC=2)C=2N=C(C)ON=2)CC1 LDFPQCYQWOWKCY-UHFFFAOYSA-N 0.000 description 2
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- ISENRXYNTDDWKI-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-3-[4-[(z)-n'-hydroxycarbamimidoyl]phenoxy]propyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)COC1=CC=C(C(\N)=N\O)C=C1 ISENRXYNTDDWKI-UHFFFAOYSA-N 0.000 description 1
- IPCDTXOKIMSQJI-UHFFFAOYSA-N tert-butyl 4-[3-(4-cyanophenoxy)-2-hydroxypropyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)COC1=CC=C(C#N)C=C1 IPCDTXOKIMSQJI-UHFFFAOYSA-N 0.000 description 1
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/05—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/18—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
-
- 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
- C07D413/10—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 carbon chain containing aromatic 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
- C07D417/14—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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (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)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Priority Applications (16)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19755268A DE19755268A1 (de) | 1997-12-12 | 1997-12-12 | Benzamidinderivate |
| SK857-2000A SK8572000A3 (en) | 1997-12-12 | 1998-11-27 | Benzamine derivatives |
| KR1020007006310A KR20010032963A (ko) | 1997-12-12 | 1998-11-27 | 벤즈아민 유도체 |
| BR9813477-9A BR9813477A (pt) | 1997-12-12 | 1998-11-27 | Derivados de benzamidina |
| PCT/EP1998/007673 WO1999031092A1 (fr) | 1997-12-12 | 1998-11-27 | DERIVES DE BENZAMIDINE UTILISES COMME INHIBITEURS DU FACTEUR DE COAGULATION Xa |
| CA002313651A CA2313651A1 (fr) | 1997-12-12 | 1998-11-27 | Derives de benzamidine utilises comme inhibiteurs du facteur de coagulation xa |
| PL98341008A PL341008A1 (en) | 1997-12-12 | 1998-11-27 | Benzamidine derivatives |
| EP98964455A EP1056743A1 (fr) | 1997-12-12 | 1998-11-27 | DERIVES DE BENZAMIDINE UTILISES COMME INHIBITEURS DU FACTEUR DE COAGULATION Xa |
| CN98812087A CN1281451A (zh) | 1997-12-12 | 1998-11-27 | 苄脒衍生物 |
| RU2000118792/04A RU2203897C2 (ru) | 1997-12-12 | 1998-11-27 | Производные бензамидина, способ их получения, фармацевтическая композиция, способ ее получения и лекарственное средство |
| HU0004353A HUP0004353A3 (en) | 1997-12-12 | 1998-11-27 | Benzamine derivatives, process for producing them and ph |
| JP2000539016A JP2002508370A (ja) | 1997-12-12 | 1998-11-27 | ベンズアミジン誘導体 |
| AU19647/99A AU744002B2 (en) | 1997-12-12 | 1998-11-27 | Benzamine derivatives |
| ZA9811339A ZA9811339B (en) | 1997-12-12 | 1998-12-10 | Benzamidine derivatives. |
| ARP980106293A AR017844A1 (es) | 1997-12-12 | 1998-12-11 | Derivados de benzamidina, procedimiento para prepararlos, empleo de los mismos para preparar un medicamento, composicion farmaceutica que los contiene yprocedimiento para obtenerla |
| NO20002958A NO20002958L (no) | 1997-12-12 | 2000-06-09 | Benzamidinderivater som koagulasjonsfaktor Xa-hemmere |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19755268A DE19755268A1 (de) | 1997-12-12 | 1997-12-12 | Benzamidinderivate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19755268A1 true DE19755268A1 (de) | 1999-06-17 |
Family
ID=7851688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19755268A Withdrawn DE19755268A1 (de) | 1997-12-12 | 1997-12-12 | Benzamidinderivate |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP1056743A1 (fr) |
| JP (1) | JP2002508370A (fr) |
| KR (1) | KR20010032963A (fr) |
| CN (1) | CN1281451A (fr) |
| AR (1) | AR017844A1 (fr) |
| AU (1) | AU744002B2 (fr) |
| BR (1) | BR9813477A (fr) |
| CA (1) | CA2313651A1 (fr) |
| DE (1) | DE19755268A1 (fr) |
| HU (1) | HUP0004353A3 (fr) |
| NO (1) | NO20002958L (fr) |
| PL (1) | PL341008A1 (fr) |
| RU (1) | RU2203897C2 (fr) |
| SK (1) | SK8572000A3 (fr) |
| WO (1) | WO1999031092A1 (fr) |
| ZA (1) | ZA9811339B (fr) |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001092214A1 (fr) * | 2000-05-31 | 2001-12-06 | Merck Patent Gmbh | Esters d'acide carbamique utilises comme inhibiteurs du facteur xa |
| WO2003047572A1 (fr) * | 2001-12-04 | 2003-06-12 | Merck Patent Gmbh | Utilisation de composes 1-phenyl-oxazolidin-2-one comme inhibiteurs de la protease m |
| US6903085B1 (en) | 1999-08-24 | 2005-06-07 | Astrazeneca, Ab | Substituted piperidine compounds useful as modulators of chemokine receptor activity |
| US6911458B2 (en) | 2000-06-20 | 2005-06-28 | Astra Zeneca | Compounds |
| US6927222B2 (en) | 2000-02-25 | 2005-08-09 | Astrazeneca Ab | Compounds |
| US6958350B2 (en) | 2001-02-19 | 2005-10-25 | Astrazeneca Ab | Chemical compounds |
| US6960602B2 (en) | 2001-03-22 | 2005-11-01 | Astrazeneca Ab | Piperidine derivatives as modulators of chemokine receptors |
| US7005439B2 (en) | 2000-06-20 | 2006-02-28 | Astrazeneca Ab | Compounds |
| US7192973B2 (en) | 2001-11-15 | 2007-03-20 | Astrazeneca Ab | Piperidine derivatives and their use as modulators of chemokine receptor activity (especially CCR5) |
| WO2007089101A1 (fr) * | 2006-01-31 | 2007-08-09 | Dong Wha Pharmaceutical Ind.Co., Ltd. | Nouveaux dérivés de benzamidine, procédé de fabrication et composition pharmaceutique les renfermant |
| US7294636B2 (en) | 2003-05-09 | 2007-11-13 | Astrazeneca Ab | Chemical compounds |
| US7345063B2 (en) | 2001-03-23 | 2008-03-18 | Astrazeneca Ab | Amides, preparation and therapeutic use as modulators of CCR-receptor activity |
| US7388020B2 (en) | 2001-03-19 | 2008-06-17 | Astrazeneca Ab | Benzimidazol derivatives modulate chemokine receptors |
| WO2009017346A1 (fr) * | 2007-07-27 | 2009-02-05 | Dong Wha Pharmaceutical Co., Ltd. | Nouveaux dérivés de benzamidine, procédé de préparation correspondant et composition pharmaceutique les contenant qui permet de prévenir ou de traiter l'ostéoporose |
| US8148405B2 (en) | 2005-08-02 | 2012-04-03 | Astrazeneca Ab | Salt I |
| US20130109672A1 (en) * | 2010-04-29 | 2013-05-02 | The United States Of America,As Represented By The Secretary, Department Of Health And Human Service | Activators of human pyruvate kinase |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU5196399A (en) * | 1998-08-11 | 2000-03-06 | Daiichi Pharmaceutical Co., Ltd. | Novel sulfonyl derivatives |
| AU2004202422B2 (en) * | 1999-12-24 | 2007-11-22 | Bayer Intellectual Property Gmbh | Substituted oxazolidinones and their use in the field of blood coagulation |
| DE19962924A1 (de) * | 1999-12-24 | 2001-07-05 | Bayer Ag | Substituierte Oxazolidinone und ihre Verwendung |
| DE10105989A1 (de) * | 2001-02-09 | 2002-08-14 | Bayer Ag | Substituierte Oxazolidinone und ihre Verwendung |
| DE10129725A1 (de) * | 2001-06-20 | 2003-01-02 | Bayer Ag | Kombinationstherapie substituierter Oxazolidinone |
| PL209135B1 (pl) * | 2002-03-06 | 2011-07-29 | Toyama Chemical Co Ltd | Pochodna aryloamidyny lub jej sól oraz środek grzybobójczy |
| DK1569912T3 (en) | 2002-12-03 | 2015-06-29 | Pharmacyclics Inc | 2- (2-hydroxybiphenyl-3-yl) -1h-benzoimidazole-5-carboxamidine derivatives as factor VIIa inhibitors. |
| DE10300111A1 (de) | 2003-01-07 | 2004-07-15 | Bayer Healthcare Ag | Verfahren zur Herstellung von 5-Chlor-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophencarboxamid |
| DE10322469A1 (de) * | 2003-05-19 | 2004-12-16 | Bayer Healthcare Ag | Heterocyclische Verbindungen |
| NZ544449A (en) * | 2003-06-23 | 2008-10-31 | Cv Therapeutics Inc | Urea derivatives of piperazines and piperidines as fatty acid oxidation inhibitors |
| DE10355461A1 (de) | 2003-11-27 | 2005-06-23 | Bayer Healthcare Ag | Verfahren zur Herstellung einer festen, oral applizierbaren pharmazeutischen Zusammensetzung |
| EP1685841A1 (fr) | 2005-01-31 | 2006-08-02 | Bayer Health Care Aktiengesellschaft | Prevention et traitement de troubles thromboemboliques |
| DE102005045518A1 (de) | 2005-09-23 | 2007-03-29 | Bayer Healthcare Ag | 2-Aminoethoxyessigsäure-Derivate und ihre Verwendung |
| AU2006299126B2 (en) | 2005-10-04 | 2012-06-28 | Bayer Intellectual Property Gmbh | Novel polymorphous form and the amorphous form of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidine-5-yl}-methyl)-2-thiophene carboxamide |
| DE102005047561A1 (de) | 2005-10-04 | 2007-04-05 | Bayer Healthcare Ag | Feste, oral applizierbare pharmazeutische Darreichungsformen mit schneller Wirkstofffreisetzung |
| DE102007018662A1 (de) | 2007-04-20 | 2008-10-23 | Bayer Healthcare Ag | Oxazolidinone zur Behandlung und Prophylaxe von pulmonaler Hypertonie |
| WO2008140220A1 (fr) * | 2007-05-09 | 2008-11-20 | Legochem Bioscience Ltd. | Inhibiteurs du facteur xa comprenant des amidines cycliques en tant que sous-unité p4, leurs procédés de préparation, et compositions pharmaceutiques et dérivés de ceux-ci |
| KR101009594B1 (ko) | 2007-05-09 | 2011-01-20 | 주식회사 레고켐 바이오사이언스 | P4 위치에 사이클릭 아미딘을 가지는 FXa 저해제, 이의유도체, 제조방법 및 이를 함유하는 의약 조성물 |
| DE102007028318A1 (de) | 2007-06-20 | 2008-12-24 | Bayer Healthcare Ag | Oxazolidinone zur Behandlung und Prophylaxe von Sepsis |
| EP2138178A1 (fr) | 2008-06-28 | 2009-12-30 | Bayer Schering Pharma Aktiengesellschaft | Oxazolidinones pour le traitement de maladie pulmonaire obstructive chronique (MPOC) et/ou de l'asthme |
| EP2140866A1 (fr) | 2008-07-04 | 2010-01-06 | Bayer Schering Pharma Aktiengesellschaft | Oxazolidinones pour le traitement d'états inflammatoires du tractus gastro-intestinal |
| CN102822167A (zh) * | 2010-01-04 | 2012-12-12 | 埃南蒂亚有限公司 | 用于制备利伐沙班的方法及其中间体 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4166132A (en) * | 1977-08-18 | 1979-08-28 | Pfizer Inc. | Antiviral amine derivatives of glycerol and propanediols |
| DE4203201A1 (de) * | 1992-02-05 | 1993-08-12 | Boehringer Ingelheim Kg | Neue amidinderivate, ihre herstellung und verwendung |
| DK0623615T3 (da) * | 1993-05-01 | 1999-12-13 | Merck Patent Gmbh | Adhæsionsreceptor-antagonister |
| ATE170179T1 (de) * | 1994-11-02 | 1998-09-15 | Merck Patent Gmbh | Adhäsionsrezeptor-antagonisten |
| DE19504954A1 (de) * | 1995-02-15 | 1996-08-22 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| DE19516483A1 (de) * | 1995-05-05 | 1996-11-07 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| ATE267011T1 (de) * | 1995-12-21 | 2004-06-15 | Bristol Myers Squibb Pharma Co | Isoxazolin, isothiazolin und pyrazolin als faktor xa inhibitoren |
| KR20010021645A (ko) * | 1997-07-11 | 2001-03-15 | 로렌스 티. 마이젠헬더 | 티아디아졸릴 및 옥사디아졸릴 페닐 옥사졸리디논 항균제 |
-
1997
- 1997-12-12 DE DE19755268A patent/DE19755268A1/de not_active Withdrawn
-
1998
- 1998-11-27 CA CA002313651A patent/CA2313651A1/fr not_active Abandoned
- 1998-11-27 SK SK857-2000A patent/SK8572000A3/sk unknown
- 1998-11-27 KR KR1020007006310A patent/KR20010032963A/ko not_active Withdrawn
- 1998-11-27 EP EP98964455A patent/EP1056743A1/fr not_active Withdrawn
- 1998-11-27 HU HU0004353A patent/HUP0004353A3/hu unknown
- 1998-11-27 BR BR9813477-9A patent/BR9813477A/pt not_active IP Right Cessation
- 1998-11-27 WO PCT/EP1998/007673 patent/WO1999031092A1/fr not_active Ceased
- 1998-11-27 CN CN98812087A patent/CN1281451A/zh active Pending
- 1998-11-27 RU RU2000118792/04A patent/RU2203897C2/ru not_active IP Right Cessation
- 1998-11-27 JP JP2000539016A patent/JP2002508370A/ja active Pending
- 1998-11-27 AU AU19647/99A patent/AU744002B2/en not_active Ceased
- 1998-11-27 PL PL98341008A patent/PL341008A1/xx unknown
- 1998-12-10 ZA ZA9811339A patent/ZA9811339B/xx unknown
- 1998-12-11 AR ARP980106293A patent/AR017844A1/es not_active Application Discontinuation
-
2000
- 2000-06-09 NO NO20002958A patent/NO20002958L/no not_active Application Discontinuation
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6903085B1 (en) | 1999-08-24 | 2005-06-07 | Astrazeneca, Ab | Substituted piperidine compounds useful as modulators of chemokine receptor activity |
| US6927222B2 (en) | 2000-02-25 | 2005-08-09 | Astrazeneca Ab | Compounds |
| US6943188B2 (en) | 2000-02-25 | 2005-09-13 | Astrazeneca Ab | Hydroxyalkyl compounds |
| US6951874B2 (en) | 2000-02-25 | 2005-10-04 | Astrazeneca Ab | Compounds |
| WO2001092214A1 (fr) * | 2000-05-31 | 2001-12-06 | Merck Patent Gmbh | Esters d'acide carbamique utilises comme inhibiteurs du facteur xa |
| US7528156B2 (en) | 2000-06-20 | 2009-05-05 | Astrazeneca Ab | Compounds |
| US6911458B2 (en) | 2000-06-20 | 2005-06-28 | Astra Zeneca | Compounds |
| US7005439B2 (en) | 2000-06-20 | 2006-02-28 | Astrazeneca Ab | Compounds |
| US6958350B2 (en) | 2001-02-19 | 2005-10-25 | Astrazeneca Ab | Chemical compounds |
| US7388020B2 (en) | 2001-03-19 | 2008-06-17 | Astrazeneca Ab | Benzimidazol derivatives modulate chemokine receptors |
| US6960602B2 (en) | 2001-03-22 | 2005-11-01 | Astrazeneca Ab | Piperidine derivatives as modulators of chemokine receptors |
| US7345063B2 (en) | 2001-03-23 | 2008-03-18 | Astrazeneca Ab | Amides, preparation and therapeutic use as modulators of CCR-receptor activity |
| US7192973B2 (en) | 2001-11-15 | 2007-03-20 | Astrazeneca Ab | Piperidine derivatives and their use as modulators of chemokine receptor activity (especially CCR5) |
| WO2003047572A1 (fr) * | 2001-12-04 | 2003-06-12 | Merck Patent Gmbh | Utilisation de composes 1-phenyl-oxazolidin-2-one comme inhibiteurs de la protease m |
| US7294636B2 (en) | 2003-05-09 | 2007-11-13 | Astrazeneca Ab | Chemical compounds |
| US8148405B2 (en) | 2005-08-02 | 2012-04-03 | Astrazeneca Ab | Salt I |
| WO2007089101A1 (fr) * | 2006-01-31 | 2007-08-09 | Dong Wha Pharmaceutical Ind.Co., Ltd. | Nouveaux dérivés de benzamidine, procédé de fabrication et composition pharmaceutique les renfermant |
| US7943646B2 (en) | 2006-01-31 | 2011-05-17 | Dong Wha Pharmaceutical Co., Ltd. | Benzamidine derivative, process for the preparation thereof and pharmaceutical composition comprising same |
| WO2009017346A1 (fr) * | 2007-07-27 | 2009-02-05 | Dong Wha Pharmaceutical Co., Ltd. | Nouveaux dérivés de benzamidine, procédé de préparation correspondant et composition pharmaceutique les contenant qui permet de prévenir ou de traiter l'ostéoporose |
| US20130109672A1 (en) * | 2010-04-29 | 2013-05-02 | The United States Of America,As Represented By The Secretary, Department Of Health And Human Service | Activators of human pyruvate kinase |
| US9708267B2 (en) | 2010-04-29 | 2017-07-18 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Activators of human pyruvate kinase |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002508370A (ja) | 2002-03-19 |
| AU1964799A (en) | 1999-07-05 |
| AR017844A1 (es) | 2001-10-24 |
| ZA9811339B (en) | 1999-07-08 |
| WO1999031092A1 (fr) | 1999-06-24 |
| PL341008A1 (en) | 2001-03-12 |
| HUP0004353A2 (hu) | 2002-03-28 |
| HUP0004353A3 (en) | 2002-04-29 |
| AU744002B2 (en) | 2002-02-14 |
| NO20002958L (no) | 2000-08-11 |
| NO20002958D0 (no) | 2000-06-09 |
| EP1056743A1 (fr) | 2000-12-06 |
| KR20010032963A (ko) | 2001-04-25 |
| BR9813477A (pt) | 2000-10-24 |
| CA2313651A1 (fr) | 1999-06-24 |
| SK8572000A3 (en) | 2001-07-10 |
| RU2203897C2 (ru) | 2003-05-10 |
| CN1281451A (zh) | 2001-01-24 |
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