NO314758B1 - Substituerte N-[(aminiminmetyl- eller aminmetyl)fenyl]- propylamider - Google Patents
Substituerte N-[(aminiminmetyl- eller aminmetyl)fenyl]- propylamider Download PDFInfo
- Publication number
- NO314758B1 NO314758B1 NO19990854A NO990854A NO314758B1 NO 314758 B1 NO314758 B1 NO 314758B1 NO 19990854 A NO19990854 A NO 19990854A NO 990854 A NO990854 A NO 990854A NO 314758 B1 NO314758 B1 NO 314758B1
- Authority
- NO
- Norway
- Prior art keywords
- carbamimidoyl
- phenyl
- hydroxy
- compound according
- compound
- Prior art date
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims description 14
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 title 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical class CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 291
- 238000000034 method Methods 0.000 claims description 109
- 150000003839 salts Chemical class 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 42
- 108010074860 Factor Xa Proteins 0.000 claims description 40
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- -1 C 1 -C 6 -alkyl Chemical group 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 108090000190 Thrombin Proteins 0.000 claims description 10
- 229960004072 thrombin Drugs 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- HQULGJDHOPDURG-UHFFFAOYSA-N 5-pyridin-2-ylthiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=CC=N1 HQULGJDHOPDURG-UHFFFAOYSA-N 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000005479 oxodihydropyridyl group Chemical group 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- GSYIVQLTSZFJRV-UHFFFAOYSA-N 3-(4-carboxyphenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC(C(O)=O)=C1 GSYIVQLTSZFJRV-UHFFFAOYSA-N 0.000 claims description 3
- YWXSPXWOLXFCBP-UHFFFAOYSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.C(N)(=N)C=1C=CC(=C(C1)CCCC1=C(C(=O)N)C=CC(=C1)C=1NC=NC1)O Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.C(N)(=N)C=1C=CC(=C(C1)CCCC1=C(C(=O)N)C=CC(=C1)C=1NC=NC1)O YWXSPXWOLXFCBP-UHFFFAOYSA-N 0.000 claims description 3
- HRCFDHWCIKKQGE-UHFFFAOYSA-N N-[3-(5-carbamimidoyl-2-hydroxyphenyl)propyl]-4-(1H-imidazol-2-yl)benzamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.NC(=N)c1ccc(O)c(CCCNC(=O)c2ccc(cc2)-c2ncc[nH]2)c1 HRCFDHWCIKKQGE-UHFFFAOYSA-N 0.000 claims description 3
- IUGURGKONYSWDW-UHFFFAOYSA-N N-[3-(5-carbamimidoyl-2-hydroxyphenyl)propyl]-4-piperidin-4-ylbenzamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.NC(=N)c1ccc(O)c(CCCNC(=O)c2ccc(cc2)C2CCNCC2)c1 IUGURGKONYSWDW-UHFFFAOYSA-N 0.000 claims description 3
- QXGGIOQOYWNMEZ-UHFFFAOYSA-N benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.NC(=O)C1=CC=CC=C1 QXGGIOQOYWNMEZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- GQOIZDFIEBHLKG-UHFFFAOYSA-N 4-tert-butyl-N-[3-(5-carbamimidoyl-2-hydroxyphenyl)propyl]benzamide 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.C(C)(C)(C)C1=CC=C(C(=O)NCCCC2=C(C=CC(=C2)C(N)=N)O)C=C1 GQOIZDFIEBHLKG-UHFFFAOYSA-N 0.000 claims description 2
- NAEPPQRSKXFIMY-UHFFFAOYSA-N FC(C(=O)O)(F)F.C(N)(=N)C=1C=CC(=C(C1)CCCNC(=O)C=1SC2=C(C1)C=CC=C2Cl)O Chemical compound FC(C(=O)O)(F)F.C(N)(=N)C=1C=CC(=C(C1)CCCNC(=O)C=1SC2=C(C1)C=CC=C2Cl)O NAEPPQRSKXFIMY-UHFFFAOYSA-N 0.000 claims description 2
- UCMFFTYQVYPZPM-UHFFFAOYSA-N N-[3-(5-carbamimidoyl-2-hydroxyphenyl)propyl]-4-phenylbenzamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)c1ccc(O)c(CCCNC(=O)c2ccc(cc2)-c2ccccc2)c1 UCMFFTYQVYPZPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 239000004305 biphenyl Chemical group 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 2
- 125000005545 phthalimidyl group Chemical group 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- WIKUFZWKQNBBGL-UHFFFAOYSA-N FC(C(=O)O)(F)F.C(N)(=N)C=1C=CC(=C(C1)CCCNC(C1=CC=C(C=C1)C1=CNC(C=C1)=O)=O)O Chemical compound FC(C(=O)O)(F)F.C(N)(=N)C=1C=CC(=C(C1)CCCNC(C1=CC=C(C=C1)C1=CNC(C=C1)=O)=O)O WIKUFZWKQNBBGL-UHFFFAOYSA-N 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims 1
- 239000000463 material Substances 0.000 description 78
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 71
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- 239000000243 solution Substances 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- 239000007921 spray Substances 0.000 description 29
- 239000002253 acid Substances 0.000 description 26
- 239000000460 chlorine Substances 0.000 description 25
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- 239000007787 solid Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 229910001868 water Inorganic materials 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 20
- 239000003146 anticoagulant agent Substances 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 150000002500 ions Chemical class 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- 229940127219 anticoagulant drug Drugs 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
- 238000002560 therapeutic procedure Methods 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- CBIRFGOMVXQXRP-NSCUHMNNSA-N 3-[(e)-3-aminoprop-1-enyl]-4-(2-methoxyethoxymethoxy)benzonitrile Chemical compound COCCOCOC1=CC=C(C#N)C=C1\C=C\CN CBIRFGOMVXQXRP-NSCUHMNNSA-N 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 11
- 150000001408 amides Chemical class 0.000 description 11
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- BMBANPOHPFKVTA-UHFFFAOYSA-N benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=O)C1=CC=CC=C1 BMBANPOHPFKVTA-UHFFFAOYSA-N 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
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- 239000000725 suspension Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000012317 TBTU Substances 0.000 description 8
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 8
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 8
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
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- 239000012458 free base Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
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- 239000012267 brine Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 206010051055 Deep vein thrombosis Diseases 0.000 description 6
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- 238000001990 intravenous administration Methods 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 208000007536 Thrombosis Diseases 0.000 description 5
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- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
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- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 4
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- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
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- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
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- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
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- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- QIDNUEGVQSCMKS-ONEGZZNKSA-N n-[(e)-3-[5-cyano-2-(2-methoxyethoxymethoxy)phenyl]prop-2-enyl]-4-(6-methoxypyridin-3-yl)benzamide Chemical compound COCCOCOC1=CC=C(C#N)C=C1\C=C\CNC(=O)C1=CC=C(C=2C=NC(OC)=CC=2)C=C1 QIDNUEGVQSCMKS-ONEGZZNKSA-N 0.000 description 1
- LNLHJOZESPRYSX-UHFFFAOYSA-N n-[3-[5-cyano-2-(2-methoxyethoxymethoxy)phenyl]propyl]-4-pyridazin-4-ylbenzamide Chemical compound COCCOCOC1=CC=C(C#N)C=C1CCCNC(=O)C1=CC=C(C=2C=NN=CC=2)C=C1 LNLHJOZESPRYSX-UHFFFAOYSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 230000017570 negative regulation of blood coagulation Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
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- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
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- ZHNFLHYOFXQIOW-LPYZJUEESA-N quinine sulfate dihydrate Chemical compound [H+].[H+].O.O.[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ZHNFLHYOFXQIOW-LPYZJUEESA-N 0.000 description 1
- WXXVQWSDMOAHHV-UHFFFAOYSA-N quinoline-7-carboxylic acid Chemical compound C1=CC=NC2=CC(C(=O)O)=CC=C21 WXXVQWSDMOAHHV-UHFFFAOYSA-N 0.000 description 1
- 159000000010 radium salts Chemical class 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- 230000007017 scission Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
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- 150000004760 silicates Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
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- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tri(ortho-tolyl)phosphine Substances CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D207/327—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
- C07C255/60—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated
-
- 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
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
- C07C259/18—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines having carbon atoms of hydroxamidine groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pyridine Compounds (AREA)
- Quinoline Compounds (AREA)
- Pyrrole Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/884,405 US6080767A (en) | 1996-01-02 | 1997-06-27 | Substituted n-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
PCT/US1998/013550 WO1999000356A1 (en) | 1997-06-27 | 1998-06-26 | Substituted n-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
Publications (3)
Publication Number | Publication Date |
---|---|
NO990854D0 NO990854D0 (no) | 1999-02-23 |
NO990854L NO990854L (no) | 1999-04-23 |
NO314758B1 true NO314758B1 (no) | 2003-05-19 |
Family
ID=25384556
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19990854A NO314758B1 (no) | 1997-06-27 | 1999-02-23 | Substituerte N-[(aminiminmetyl- eller aminmetyl)fenyl]- propylamider |
Country Status (28)
Country | Link |
---|---|
US (1) | US6080767A (ru) |
EP (1) | EP0931060B1 (ru) |
JP (1) | JP4107687B2 (ru) |
KR (1) | KR100567148B1 (ru) |
CN (1) | CN1221529C (ru) |
AP (1) | AP1061A (ru) |
AT (1) | ATE449759T1 (ru) |
AU (1) | AU741173B2 (ru) |
BG (1) | BG64867B1 (ru) |
BR (1) | BR9806060B1 (ru) |
CA (1) | CA2264556C (ru) |
CZ (1) | CZ299399B6 (ru) |
DE (1) | DE69841300D1 (ru) |
DK (1) | DK0931060T3 (ru) |
EA (1) | EA002358B1 (ru) |
ES (1) | ES2335825T3 (ru) |
HK (1) | HK1022685A1 (ru) |
HU (1) | HU228982B1 (ru) |
IL (1) | IL128653A (ru) |
NO (1) | NO314758B1 (ru) |
OA (1) | OA10981A (ru) |
PL (1) | PL191115B1 (ru) |
PT (1) | PT931060E (ru) |
SI (1) | SI0931060T1 (ru) |
SK (1) | SK286615B6 (ru) |
UA (1) | UA66346C2 (ru) |
WO (1) | WO1999000356A1 (ru) |
ZA (1) | ZA985664B (ru) |
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US6740682B2 (en) * | 1997-08-29 | 2004-05-25 | Tularik Limited | Meta-benzamidine derivatives as serine protease inhibitors |
WO2000047553A2 (en) * | 1999-02-11 | 2000-08-17 | Cor Therapeutics Inc. | ALKENYL AND ALKYNYL COMPOUNDS AS INHIBITORS OF FACTOR Xa |
DE10012732A1 (de) | 2000-03-18 | 2001-09-20 | Aventis Behring Gmbh | Thrombin-Zubereitungen und Verfahren zu ihrer Herstellung |
SE0001803D0 (sv) | 2000-05-16 | 2000-05-16 | Astrazeneca Ab | New compounds i |
GB0108903D0 (en) * | 2000-10-05 | 2001-05-30 | Aventis Pharm Prod Inc | Novel crystalline forms of a factor Xa inhibitor |
US6982251B2 (en) * | 2000-12-20 | 2006-01-03 | Schering Corporation | Substituted 2-azetidinones useful as hypocholesterolemic agents |
US20020183519A1 (en) * | 2001-03-13 | 2002-12-05 | Herbert Nar | Antithrombotic carboxylic acid amides |
GB0124938D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124933D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124931D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124934D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124941D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124936D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124939D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
DK1474395T3 (da) * | 2002-02-12 | 2008-02-11 | Smithkline Beecham Corp | Nicotinamidderivater, der er nyttige som p38-inhibitorer |
GB0217757D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
EP1394159A1 (fr) * | 2002-08-13 | 2004-03-03 | Warner-Lambert Company LLC | Nouveaux dérivés de thiophène, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent |
PT1569912E (pt) | 2002-12-03 | 2015-09-15 | Pharmacyclics Llc | Derivados 2-(2-hidroxibifenil-3-il)-1h-benzoimidazole-5- carboxamidina como inibidores do fator viia |
GB0230162D0 (en) * | 2002-12-24 | 2003-02-05 | Metris Therapeutics Ltd | Compounds useful in inhibiting angiogenesis |
US7235543B2 (en) | 2003-03-07 | 2007-06-26 | Schering Corporation | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
JP4589919B2 (ja) * | 2003-03-07 | 2010-12-01 | シェーリング コーポレイション | 高コレステロール血症の処置のための、置換アゼチジノン化合物、これらの処方物および使用 |
CN1756755A (zh) * | 2003-03-07 | 2006-04-05 | 先灵公司 | 取代的2-吖丁啶酮化合物、其制剂及其治疗高胆甾醇血症的用途 |
GB0308185D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
WO2005033079A1 (ja) * | 2003-09-30 | 2005-04-14 | Eisai Co., Ltd. | ヘテロ環化合物を含有する新規な抗真菌剤 |
GB0402143D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
RU2006138036A (ru) * | 2004-03-30 | 2008-05-10 | Чирон Корпорейшн (Us) | Производные замещенного тиофена в качестве противораковых средств |
US20050241110A1 (en) * | 2004-04-09 | 2005-11-03 | Bruce Baker | Ergonomic handles, especially for garden tools |
US7563780B1 (en) * | 2004-06-18 | 2009-07-21 | Advanced Cardiovascular Systems, Inc. | Heparin prodrugs and drug delivery stents formed therefrom |
US20090227799A1 (en) * | 2004-08-09 | 2009-09-10 | Kazutaka Nakamoto | Novel Antimalarial Agent Containing Heterocyclic Compound |
US20080051416A1 (en) * | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
JP4874958B2 (ja) | 2005-03-30 | 2012-02-15 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ピリジン誘導体を含有する抗真菌剤 |
GB0512429D0 (en) * | 2005-06-17 | 2005-07-27 | Smithkline Beecham Corp | Novel compound |
TWI385169B (zh) * | 2005-10-31 | 2013-02-11 | Eisai R&D Man Co Ltd | 經雜環取代之吡啶衍生物及含有彼之抗真菌劑 |
HUE041300T2 (hu) * | 2006-06-26 | 2019-05-28 | Akebia Therapeutics Inc | Prolilhidroxiláz inhibitorok és alkalmazási eljárások |
WO2008035726A1 (fr) * | 2006-09-21 | 2008-03-27 | Eisai R & D Management Co., Ltd. | Dérivé de pyridine substitué par un cycle hétéroaryle, et agent antifongique le comprenant |
KR20100015897A (ko) * | 2007-04-27 | 2010-02-12 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 헤테로환 치환 피리딘 유도체의 염 또는 그의 결정 |
TW200841879A (en) * | 2007-04-27 | 2008-11-01 | Eisai R&D Man Co Ltd | Pyridine derivatives substituted by heterocyclic ring and phosphonoamino group, and anti-fungal agent containing same |
US8513287B2 (en) | 2007-12-27 | 2013-08-20 | Eisai R&D Management Co., Ltd. | Heterocyclic ring and phosphonoxymethyl group substituted pyridine derivatives and antifungal agent containing same |
US8188119B2 (en) * | 2008-10-24 | 2012-05-29 | Eisai R&D Management Co., Ltd | Pyridine derivatives substituted with heterocyclic ring and γ-glutamylamino group, and antifungal agents containing same |
GB0919194D0 (en) | 2009-11-02 | 2009-12-16 | Lytix Biopharma As | Compounds |
RU2608611C2 (ru) | 2009-11-05 | 2017-01-23 | Юниверсити Оф Нотр Дам Дю Лак | СОЕДИНЕНИЯ ИМИДАЗО[1,2-а] ПИРИДИНА, ИХ СИНТЕЗ И СПОСОБЫ ПРИМЕНЕНИЯ |
NZ602311A (en) * | 2010-03-18 | 2014-08-29 | Pasteur Institut Korea | Anti-infective compounds |
KR101844623B1 (ko) | 2011-03-29 | 2018-04-02 | 사노피 | 안정성이 향상된 오타믹사반 제제 |
SG193612A1 (en) * | 2011-03-29 | 2013-11-29 | Sanofi Sa | Benzoic acid salt of otamixaban |
CA2841905A1 (en) | 2011-07-26 | 2013-01-31 | Sanofi | 3-heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals |
WO2013042782A1 (ja) | 2011-09-22 | 2013-03-28 | 武田薬品工業株式会社 | 縮合複素環化合物 |
MX2018003294A (es) | 2015-09-17 | 2019-04-25 | J Miller Marvin | Compuestos heterociclicos que contienen bencilamina y composiciones utiles contra infeccion por micobacterias. |
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US5424334A (en) * | 1991-12-19 | 1995-06-13 | G. D. Searle & Co. | Peptide mimetic compounds useful as platelet aggregation inhibitors |
US5612353A (en) * | 1995-06-07 | 1997-03-18 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
SI0906094T1 (en) * | 1996-01-02 | 2003-12-31 | Aventis Pharmaceuticals Inc. | Substituted n- (aminoiminomethyl or aminomethyl)phenyl)propyl amides |
-
1997
- 1997-06-27 US US08/884,405 patent/US6080767A/en not_active Expired - Lifetime
-
1998
- 1998-06-26 JP JP50587099A patent/JP4107687B2/ja not_active Expired - Fee Related
- 1998-06-26 IL IL12865398A patent/IL128653A/en not_active IP Right Cessation
- 1998-06-26 AT AT98931728T patent/ATE449759T1/de active
- 1998-06-26 EP EP98931728A patent/EP0931060B1/en not_active Expired - Lifetime
- 1998-06-26 SK SK220-99A patent/SK286615B6/sk not_active IP Right Cessation
- 1998-06-26 DE DE69841300T patent/DE69841300D1/de not_active Expired - Lifetime
- 1998-06-26 CZ CZ0064799A patent/CZ299399B6/cs not_active IP Right Cessation
- 1998-06-26 UA UA99031713A patent/UA66346C2/ru unknown
- 1998-06-26 BR BRPI9806060-0A patent/BR9806060B1/pt not_active IP Right Cessation
- 1998-06-26 ES ES98931728T patent/ES2335825T3/es not_active Expired - Lifetime
- 1998-06-26 CN CNB988010844A patent/CN1221529C/zh not_active Expired - Lifetime
- 1998-06-26 AU AU81771/98A patent/AU741173B2/en not_active Expired
- 1998-06-26 HU HU0202655A patent/HU228982B1/hu unknown
- 1998-06-26 DK DK98931728.4T patent/DK0931060T3/da active
- 1998-06-26 WO PCT/US1998/013550 patent/WO1999000356A1/en active IP Right Grant
- 1998-06-26 AP APAP/P/1999/001467A patent/AP1061A/en active
- 1998-06-26 KR KR1019997001592A patent/KR100567148B1/ko not_active IP Right Cessation
- 1998-06-26 EA EA199900239A patent/EA002358B1/ru not_active IP Right Cessation
- 1998-06-26 PL PL331985A patent/PL191115B1/pl unknown
- 1998-06-26 SI SI9830924T patent/SI0931060T1/sl unknown
- 1998-06-26 PT PT98931728T patent/PT931060E/pt unknown
- 1998-06-26 CA CA002264556A patent/CA2264556C/en not_active Expired - Lifetime
- 1998-06-29 ZA ZA985664A patent/ZA985664B/xx unknown
-
1999
- 1999-02-23 NO NO19990854A patent/NO314758B1/no not_active IP Right Cessation
- 1999-02-25 OA OA9900040A patent/OA10981A/en unknown
- 1999-03-18 BG BG103264A patent/BG64867B1/bg unknown
-
2000
- 2000-03-21 HK HK00101706A patent/HK1022685A1/xx not_active IP Right Cessation
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