OA10981A - Substituted n-Ä(aminoiminomethyl or aminomethyl)p henylÜpropyl amides - Google Patents
Substituted n-Ä(aminoiminomethyl or aminomethyl)p henylÜpropyl amides Download PDFInfo
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- OA10981A OA10981A OA9900040A OA9900040A OA10981A OA 10981 A OA10981 A OA 10981A OA 9900040 A OA9900040 A OA 9900040A OA 9900040 A OA9900040 A OA 9900040A OA 10981 A OA10981 A OA 10981A
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- prodrug
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- -1 aminoiminomethyl Chemical group 0.000 title claims description 72
- 150000001408 amides Chemical class 0.000 title claims description 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 674
- 108010074860 Factor Xa Proteins 0.000 claims abstract description 39
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 190
- 239000000203 mixture Substances 0.000 claims description 101
- 239000000651 prodrug Substances 0.000 claims description 59
- 229940002612 prodrug Drugs 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- 239000001257 hydrogen Substances 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 125000001072 heteroaryl group Chemical group 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 108090000190 Thrombin Proteins 0.000 claims description 14
- 230000015572 biosynthetic process Effects 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 229960004072 thrombin Drugs 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 claims description 6
- 125000003435 aroyl group Chemical group 0.000 claims description 5
- 125000005215 cycloalkylheteroaryl group Chemical group 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 3
- 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 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
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 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 1
- 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 1
- JPIONSXLJKFEHX-UHFFFAOYSA-N N-[3-(5-carbamimidoyl-2-hydroxyphenyl)propyl]-4-pyridazin-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)-c2ccnnc2)c1 JPIONSXLJKFEHX-UHFFFAOYSA-N 0.000 claims 1
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 14
- 239000003112 inhibitor Substances 0.000 abstract description 11
- 230000001668 ameliorated effect Effects 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 153
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 121
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 104
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 75
- 239000002253 acid Substances 0.000 description 71
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 66
- 239000000047 product Substances 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 52
- 235000019439 ethyl acetate Nutrition 0.000 description 51
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 46
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 41
- 239000000463 material Substances 0.000 description 40
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- 235000002639 sodium chloride Nutrition 0.000 description 36
- 239000007787 solid Substances 0.000 description 36
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 238000003756 stirring Methods 0.000 description 33
- 150000003839 salts Chemical class 0.000 description 30
- 238000004007 reversed phase HPLC Methods 0.000 description 29
- 150000002500 ions Chemical class 0.000 description 27
- 229940125773 compound 10 Drugs 0.000 description 26
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 26
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 25
- 150000002466 imines Chemical class 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- 125000006413 ring segment Chemical group 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
- 125000004429 atom Chemical group 0.000 description 22
- 239000012043 crude product Substances 0.000 description 22
- 239000007921 spray Substances 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 21
- 229910052799 carbon Inorganic materials 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- 229940093499 ethyl acetate Drugs 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 18
- 150000003254 radicals Chemical class 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 16
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 16
- 239000003146 anticoagulant agent Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 150000003952 β-lactams Chemical class 0.000 description 15
- 208000007536 Thrombosis Diseases 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 239000012467 final product Substances 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- ZBELDPMWYXDLNY-UHFFFAOYSA-N methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate Chemical compound C12=C3SC(C(=N)OC)=NC3=CC=C2N=CN=C1NC1=CC=C(Br)C=C1F ZBELDPMWYXDLNY-UHFFFAOYSA-N 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
- 230000010933 acylation Effects 0.000 description 11
- 238000005917 acylation reaction Methods 0.000 description 11
- 239000012267 brine Substances 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- JPVUWCPKMYXOKW-UHFFFAOYSA-N 4-phenylbenzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1C1=CC=CC=C1 JPVUWCPKMYXOKW-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- 150000001204 N-oxides Chemical class 0.000 description 10
- 241000206607 Porphyra umbilicalis Species 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
- 125000004122 cyclic group Chemical group 0.000 description 10
- 238000004949 mass spectrometry Methods 0.000 description 10
- 239000001301 oxygen Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000012317 TBTU Substances 0.000 description 9
- 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 9
- 229940127219 anticoagulant drug Drugs 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 238000007429 general method Methods 0.000 description 9
- 229910052717 sulfur Inorganic materials 0.000 description 9
- 0 C[C@]([C@@](Cc1cc(C(N)=N)ccc1)C(*)=O)N*(c(cc1)cc2c1C1=CC=CCC21C)=O Chemical compound C[C@]([C@@](Cc1cc(C(N)=N)ccc1)C(*)=O)N*(c(cc1)cc2c1C1=CC=CCC21C)=O 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 241000534944 Thia Species 0.000 description 8
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 8
- 239000012458 free base Substances 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 229960002897 heparin Drugs 0.000 description 7
- 229920000669 heparin Polymers 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 125000004434 sulfur atom Chemical group 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 210000003462 vein Anatomy 0.000 description 7
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 6
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 6
- 229940123583 Factor Xa inhibitor Drugs 0.000 description 6
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000006978 adaptation Effects 0.000 description 6
- 230000002785 anti-thrombosis Effects 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 230000017531 blood circulation Effects 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
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- 239000000523 sample Substances 0.000 description 6
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 5
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 5
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- 101150041968 CDC13 gene Proteins 0.000 description 5
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- 241001465754 Metazoa Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 206010047249 Venous thrombosis Diseases 0.000 description 5
- 210000001367 artery Anatomy 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
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- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 238000001038 ionspray mass spectrometry Methods 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
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- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 4
- 206010003178 Arterial thrombosis Diseases 0.000 description 4
- ISMDILRWKSYCOD-GNKBHMEESA-N C(C1=CC=CC=C1)[C@@H]1NC(OCCCCCCCCCCCNC([C@@H](NC(C[C@@H]1O)=O)C(C)C)=O)=O Chemical compound C(C1=CC=CC=C1)[C@@H]1NC(OCCCCCCCCCCCNC([C@@H](NC(C[C@@H]1O)=O)C(C)C)=O)=O ISMDILRWKSYCOD-GNKBHMEESA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- 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
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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
-
- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/08—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing three- or four-membered rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (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)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- 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 (1)
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 |
Publications (1)
Publication Number | Publication Date |
---|---|
OA10981A true OA10981A (en) | 2001-11-01 |
Family
ID=25384556
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
OA9900040A OA10981A (en) | 1997-06-27 | 1999-02-25 | Substituted n-Ä(aminoiminomethyl or aminomethyl)p henylÜpropyl amides |
Country Status (28)
Country | Link |
---|---|
US (1) | US6080767A (de) |
EP (1) | EP0931060B1 (de) |
JP (1) | JP4107687B2 (de) |
KR (1) | KR100567148B1 (de) |
CN (1) | CN1221529C (de) |
AP (1) | AP1061A (de) |
AT (1) | ATE449759T1 (de) |
AU (1) | AU741173B2 (de) |
BG (1) | BG64867B1 (de) |
BR (1) | BR9806060B1 (de) |
CA (1) | CA2264556C (de) |
CZ (1) | CZ299399B6 (de) |
DE (1) | DE69841300D1 (de) |
DK (1) | DK0931060T3 (de) |
EA (1) | EA002358B1 (de) |
ES (1) | ES2335825T3 (de) |
HK (1) | HK1022685A1 (de) |
HU (1) | HU228982B1 (de) |
IL (1) | IL128653A (de) |
NO (1) | NO314758B1 (de) |
OA (1) | OA10981A (de) |
PL (1) | PL191115B1 (de) |
PT (1) | PT931060E (de) |
SI (1) | SI0931060T1 (de) |
SK (1) | SK286615B6 (de) |
UA (1) | UA66346C2 (de) |
WO (1) | WO1999000356A1 (de) |
ZA (1) | ZA985664B (de) |
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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 (de) * | 2002-08-13 | 2004-03-03 | Warner-Lambert Company LLC | Neue Thiophen-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen |
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. |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
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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/de 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/uk 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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