IL118278A - Transformed benzyloxycarbonylguanidines, process for their preparation, and pharmaceutical preparations containing them - Google Patents
Transformed benzyloxycarbonylguanidines, process for their preparation, and pharmaceutical preparations containing themInfo
- Publication number
- IL118278A IL118278A IL11827896A IL11827896A IL118278A IL 118278 A IL118278 A IL 118278A IL 11827896 A IL11827896 A IL 11827896A IL 11827896 A IL11827896 A IL 11827896A IL 118278 A IL118278 A IL 118278A
- Authority
- IL
- Israel
- Prior art keywords
- independently
- another
- hydrogen
- group
- alkyl
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims description 29
- 238000000034 method Methods 0.000 title description 28
- 230000008569 process Effects 0.000 title description 5
- 238000002360 preparation method Methods 0.000 title description 4
- FZOCFRPFPKJHHP-UHFFFAOYSA-N benzyl n-(diaminomethylidene)carbamate Chemical class NC(N)=NC(=O)OCC1=CC=CC=C1 FZOCFRPFPKJHHP-UHFFFAOYSA-N 0.000 title description 3
- 239000001257 hydrogen Substances 0.000 claims abstract description 212
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 212
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 162
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 159
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 105
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 104
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 97
- -1 methoxy, hydroxyl Chemical group 0.000 claims abstract description 66
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- 125000001424 substituent group Chemical group 0.000 claims abstract description 56
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 48
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 45
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 37
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000001301 oxygen Substances 0.000 claims abstract description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 239000002253 acid Substances 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims abstract description 16
- 150000007513 acids Chemical class 0.000 claims abstract description 9
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims abstract 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 49
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 46
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 44
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 30
- 150000001721 carbon Chemical group 0.000 claims description 24
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 23
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 23
- 229960004198 guanidine Drugs 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 125000002883 imidazolyl group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 10
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 10
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 10
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 7
- 210000000056 organ Anatomy 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 238000011321 prophylaxis Methods 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 5
- 206010061216 Infarction Diseases 0.000 claims description 4
- ZTTLASLZGMTEBH-UHFFFAOYSA-N [2-chloro-5-(trifluoromethyl)phenyl]methyl n-(diaminomethylidene)carbamate;hydrochloride Chemical compound Cl.NC(N)=NC(=O)OCC1=CC(C(F)(F)F)=CC=C1Cl ZTTLASLZGMTEBH-UHFFFAOYSA-N 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 230000007574 infarction Effects 0.000 claims description 4
- 230000000302 ischemic effect Effects 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- XOZVHVVFSDGFSY-UHFFFAOYSA-N (3-propan-2-ylphenyl)methyl n-(diaminomethylidene)carbamate;hydrochloride Chemical compound Cl.CC(C)C1=CC=CC(COC(=O)N=C(N)N)=C1 XOZVHVVFSDGFSY-UHFFFAOYSA-N 0.000 claims description 3
- MEDGDWUZMZKJIQ-UHFFFAOYSA-N 1-carbamimidoyl-1-[(3,4-dichlorophenyl)methyl]-3-methylurea;hydrochloride Chemical compound Cl.CNC(=O)N(C(N)=N)CC1=CC=C(Cl)C(Cl)=C1 MEDGDWUZMZKJIQ-UHFFFAOYSA-N 0.000 claims description 3
- AYOOQCPGFQKDBK-UHFFFAOYSA-N 1-carbamimidoyl-1-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]-3-methylurea;hydrochloride Chemical compound Cl.CNC(=O)N(C(N)=N)CC1=CC=C(F)C(C(F)(F)F)=C1 AYOOQCPGFQKDBK-UHFFFAOYSA-N 0.000 claims description 3
- FFZOIJHZOIGCDN-UHFFFAOYSA-N 1-carbamimidoyl-1-methyl-3-[(3-methylsulfonyl-4-phenoxyphenyl)methyl]urea;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(=O)(=O)C1=CC(CNC(=O)N(C(N)=N)C)=CC=C1OC1=CC=CC=C1 FFZOIJHZOIGCDN-UHFFFAOYSA-N 0.000 claims description 3
- XQNVTOUUGHRJIT-UHFFFAOYSA-N 1-carbamimidoyl-1-methyl-3-[(3-methylsulfonyl-4-propan-2-ylphenyl)methyl]urea;methanesulfonic acid Chemical compound CS(O)(=O)=O.CC(C)C1=CC=C(CNC(=O)N(C)C(N)=N)C=C1S(C)(=O)=O XQNVTOUUGHRJIT-UHFFFAOYSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 206010003119 arrhythmia Diseases 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 3
- 206010020718 hyperplasia Diseases 0.000 claims description 3
- 230000002093 peripheral effect Effects 0.000 claims description 3
- 125000004620 quinolinyl-N-oxide group Chemical group 0.000 claims description 3
- 230000035939 shock Effects 0.000 claims description 3
- RNINTZTVHIJZNQ-UHFFFAOYSA-N (2,3,6-trifluorophenyl)methyl n-(diaminomethylidene)carbamate;hydrochloride Chemical compound Cl.NC(N)=NC(=O)OCC1=C(F)C=CC(F)=C1F RNINTZTVHIJZNQ-UHFFFAOYSA-N 0.000 claims description 2
- SCOWUCRWGRQSKH-UHFFFAOYSA-N (3-methylsulfonyl-4-propan-2-ylphenyl)methyl n-(diaminomethylidene)carbamate;hydrochloride Chemical compound Cl.CC(C)C1=CC=C(COC(=O)N=C(N)N)C=C1S(C)(=O)=O SCOWUCRWGRQSKH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- IWCWJRYHQVOQRL-UHFFFAOYSA-N 1-carbamimidoyl-1-[[2-chloro-5-(trifluoromethyl)phenyl]methyl]-3-methylurea;hydrochloride Chemical compound Cl.CNC(=O)N(C(N)=N)CC1=CC(C(F)(F)F)=CC=C1Cl IWCWJRYHQVOQRL-UHFFFAOYSA-N 0.000 claims description 2
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 206010019668 Hepatic fibrosis Diseases 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- RMKIADKIUILBFL-UHFFFAOYSA-N [4-methoxy-3-(trifluoromethyl)phenyl]methyl n-(diaminomethylidene)carbamate;hydrochloride Chemical compound Cl.COC1=CC=C(COC(=O)N=C(N)N)C=C1C(F)(F)F RMKIADKIUILBFL-UHFFFAOYSA-N 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 230000000879 anti-atherosclerotic effect Effects 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims description 2
- 230000004663 cell proliferation Effects 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 230000003176 fibrotic effect Effects 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
- 201000002793 renal fibrosis Diseases 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims 2
- FMOOEJZQTMGEFK-UHFFFAOYSA-N (3-methylsulfonyl-4-quinolin-6-yloxyphenyl)methyl n-(diaminomethylidene)carbamate;dihydrochloride Chemical compound Cl.Cl.CS(=O)(=O)C1=CC(COC(=O)N=C(N)N)=CC=C1OC1=CC=C(N=CC=C2)C2=C1 FMOOEJZQTMGEFK-UHFFFAOYSA-N 0.000 claims 1
- FYGQFSWSLTWXEY-UHFFFAOYSA-N 1-(diaminomethylidene)-3-[(2,5-difluorophenyl)methyl]urea;hydrochloride Chemical compound Cl.NC(N)=NC(=O)NCC1=CC(F)=CC=C1F FYGQFSWSLTWXEY-UHFFFAOYSA-N 0.000 claims 1
- FFXFOLIHTZYERQ-UHFFFAOYSA-N 1-(diaminomethylidene)-3-[(2-fluorophenyl)methyl]urea;hydrochloride Chemical compound Cl.NC(N)=NC(=O)NCC1=CC=CC=C1F FFXFOLIHTZYERQ-UHFFFAOYSA-N 0.000 claims 1
- HHVIJYWDLDIVAV-UHFFFAOYSA-N 1-(diaminomethylidene)-3-[(3,5-difluorophenyl)methyl]urea;hydrochloride Chemical compound Cl.NC(N)=NC(=O)NCC1=CC(F)=CC(F)=C1 HHVIJYWDLDIVAV-UHFFFAOYSA-N 0.000 claims 1
- RGOOSBAFKGQNDK-UHFFFAOYSA-N 1-(diaminomethylidene)-3-[(3,5-dimethylphenyl)methyl]urea;hydrochloride Chemical compound Cl.CC1=CC(C)=CC(CNC(=O)N=C(N)N)=C1 RGOOSBAFKGQNDK-UHFFFAOYSA-N 0.000 claims 1
- ITWFWANFFTUVLO-UHFFFAOYSA-N 1-(diaminomethylidene)-3-[(3-fluorophenyl)methyl]urea;hydrochloride Chemical compound Cl.NC(N)=NC(=O)NCC1=CC=CC(F)=C1 ITWFWANFFTUVLO-UHFFFAOYSA-N 0.000 claims 1
- ZAKMLKUFCQYNIA-UHFFFAOYSA-N 1-(diaminomethylidene)-3-[(3-methylphenyl)methyl]urea;hydrochloride Chemical compound Cl.CC1=CC=CC(CNC(=O)N=C(N)N)=C1 ZAKMLKUFCQYNIA-UHFFFAOYSA-N 0.000 claims 1
- BBRAUBVZDDLAIW-UHFFFAOYSA-N 1-(diaminomethylidene)-3-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]urea;hydrochloride Chemical compound Cl.NC(N)=NC(=O)NCC1=CC(F)=CC(C(F)(F)F)=C1 BBRAUBVZDDLAIW-UHFFFAOYSA-N 0.000 claims 1
- JHMVEDKZNGSUKS-UHFFFAOYSA-N 1-(diaminomethylidene)-3-[[4-(dimethylamino)phenyl]methyl]urea;hydrochloride Chemical compound Cl.CN(C)C1=CC=C(CNC(=O)NC(N)=N)C=C1 JHMVEDKZNGSUKS-UHFFFAOYSA-N 0.000 claims 1
- UTOLKUXYLWGTLQ-UHFFFAOYSA-N 1-[(3-bromo-5-fluorophenyl)methyl]-3-(diaminomethylidene)urea;hydrochloride Chemical compound Cl.NC(N)=NC(=O)NCC1=CC(F)=CC(Br)=C1 UTOLKUXYLWGTLQ-UHFFFAOYSA-N 0.000 claims 1
- DTSLLVDTGYVKRL-UHFFFAOYSA-N Cl.FC1=C(CN(C(=N)N)C(=O)N)C(=CC=C1)F Chemical compound Cl.FC1=C(CN(C(=N)N)C(=O)N)C(=CC=C1)F DTSLLVDTGYVKRL-UHFFFAOYSA-N 0.000 claims 1
- ADZNMUGOJGYKGD-UHFFFAOYSA-N NC(N)=NC(=O)OCC1=CC(F)=CC=C1F Chemical compound NC(N)=NC(=O)OCC1=CC(F)=CC=C1F ADZNMUGOJGYKGD-UHFFFAOYSA-N 0.000 claims 1
- DOOUMOMSIXOYFO-UHFFFAOYSA-N [4-(2-methylquinolin-6-yl)oxy-3-(trifluoromethyl)phenyl]methyl n-(diaminomethylidene)carbamate;dihydrochloride Chemical compound Cl.Cl.C1=CC2=NC(C)=CC=C2C=C1OC1=CC=C(COC(=O)N=C(N)N)C=C1C(F)(F)F DOOUMOMSIXOYFO-UHFFFAOYSA-N 0.000 claims 1
- MANCPDUJJHRYJZ-UHFFFAOYSA-N [4-(2-methylquinolin-6-yl)oxy-3-methylsulfonylphenyl]methyl n-(diaminomethylidene)carbamate;dihydrochloride Chemical compound Cl.Cl.C1=CC2=NC(C)=CC=C2C=C1OC1=CC=C(COC(=O)N=C(N)N)C=C1S(C)(=O)=O MANCPDUJJHRYJZ-UHFFFAOYSA-N 0.000 claims 1
- VCDVXXHOFGQKQK-UHFFFAOYSA-N [4-pyridin-3-yloxy-3-(trifluoromethyl)phenyl]methyl n-(diaminomethylidene)carbamate;dihydrochloride Chemical compound Cl.Cl.FC(F)(F)C1=CC(COC(=O)N=C(N)N)=CC=C1OC1=CC=CN=C1 VCDVXXHOFGQKQK-UHFFFAOYSA-N 0.000 claims 1
- 238000003745 diagnosis Methods 0.000 claims 1
- 210000001428 peripheral nervous system Anatomy 0.000 claims 1
- 238000004321 preservation Methods 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 25
- 239000000243 solution Substances 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 19
- 235000011167 hydrochloric acid Nutrition 0.000 description 12
- 229960000443 hydrochloric acid Drugs 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000004941 influx Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 3
- WOPLIOPJEJRFST-UHFFFAOYSA-N 3-methylsulfonyl-4-phenoxybenzoic acid Chemical compound CS(=O)(=O)C1=CC(C(O)=O)=CC=C1OC1=CC=CC=C1 WOPLIOPJEJRFST-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- LPMXVESGRSUGHW-GHYGWZAOSA-N Ouabain Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1)[C@H]1C[C@@H](O)[C@@]2(CO)[C@@](O)(C1)CC[C@H]1[C@]3(O)[C@@](C)([C@H](C4=CC(=O)OC4)CC3)C[C@@H](O)[C@H]21 LPMXVESGRSUGHW-GHYGWZAOSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical class ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 244000166550 Strophanthus gratus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
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- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
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- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
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- GHNGBFHLUOJHKP-UHFFFAOYSA-N methyl 3-iodo-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(I)=C1 GHNGBFHLUOJHKP-UHFFFAOYSA-N 0.000 description 1
- IRYBOHVMFKZODT-UHFFFAOYSA-N methyl 4-fluoro-3-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC=C(F)C(C(F)(F)F)=C1 IRYBOHVMFKZODT-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
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- AJDQRQQNNLZLPM-UHFFFAOYSA-N n-(diaminomethylidene)benzamide Chemical class NC(N)=NC(=O)C1=CC=CC=C1 AJDQRQQNNLZLPM-UHFFFAOYSA-N 0.000 description 1
- CWPKGNODLGNSMD-UHFFFAOYSA-N n-methyl-1-(3-methylsulfonyl-4-phenoxyphenyl)methanamine Chemical compound CS(=O)(=O)C1=CC(CNC)=CC=C1OC1=CC=CC=C1 CWPKGNODLGNSMD-UHFFFAOYSA-N 0.000 description 1
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- 239000003380 propellant Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- OVYWMEWYEJLIER-UHFFFAOYSA-N quinolin-6-ol Chemical compound N1=CC=CC2=CC(O)=CC=C21 OVYWMEWYEJLIER-UHFFFAOYSA-N 0.000 description 1
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LAYPMCGIWDGYKX-UHFFFAOYSA-N trichloromethyl hydrogen carbonate Chemical compound OC(=O)OC(Cl)(Cl)Cl LAYPMCGIWDGYKX-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/10—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by doubly-bound oxygen atoms
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/24—Y being a hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/22—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide 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
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/46—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
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- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
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- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
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- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Physics & Mathematics (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19518073A DE19518073A1 (de) | 1995-05-17 | 1995-05-17 | Substituierte Benzyloxycarbonylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL118278A0 IL118278A0 (en) | 1996-09-12 |
| IL118278A true IL118278A (en) | 2001-06-14 |
Family
ID=7762133
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL11827896A IL118278A (en) | 1995-05-17 | 1996-05-15 | Transformed benzyloxycarbonylguanidines, process for their preparation, and pharmaceutical preparations containing them |
Country Status (29)
| Country | Link |
|---|---|
| US (2) | US5753710A (pt) |
| EP (1) | EP0748795B1 (pt) |
| JP (1) | JP3962110B2 (pt) |
| KR (1) | KR960040130A (pt) |
| CN (1) | CN1062555C (pt) |
| AR (1) | AR002741A1 (pt) |
| AT (1) | ATE195726T1 (pt) |
| AU (1) | AU701567B2 (pt) |
| BR (1) | BR9602337A (pt) |
| CA (1) | CA2176796C (pt) |
| CZ (1) | CZ288332B6 (pt) |
| DE (2) | DE19518073A1 (pt) |
| DK (1) | DK0748795T3 (pt) |
| ES (1) | ES2149403T3 (pt) |
| GR (1) | GR3034573T3 (pt) |
| HR (1) | HRP960221B1 (pt) |
| HU (1) | HUP9601321A3 (pt) |
| IL (1) | IL118278A (pt) |
| MY (1) | MY115805A (pt) |
| NO (1) | NO306156B1 (pt) |
| NZ (1) | NZ286583A (pt) |
| PL (1) | PL183629B1 (pt) |
| PT (1) | PT748795E (pt) |
| RU (1) | RU2188191C2 (pt) |
| SI (1) | SI0748795T1 (pt) |
| SK (1) | SK282010B6 (pt) |
| TR (1) | TR199600400A2 (pt) |
| TW (1) | TW355705B (pt) |
| ZA (1) | ZA963893B (pt) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19960204A1 (de) * | 1999-12-14 | 2001-06-28 | Aventis Pharma Gmbh | Substituierte Norlbornylamino-Derivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| US6740776B2 (en) | 2001-07-16 | 2004-05-25 | Novartis Ag | Air oxidation of an aromatic aldehyde to an aromatic acid |
| ES2628850T3 (es) * | 2011-03-15 | 2017-08-04 | Astellas Pharma Inc. | Compuesto de guanidina |
| WO2013113776A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| CN104220427A (zh) | 2012-02-03 | 2014-12-17 | 巴斯夫欧洲公司 | 杀真菌嘧啶化合物 |
| CN104220428A (zh) | 2012-02-03 | 2014-12-17 | 巴斯夫欧洲公司 | 杀真菌嘧啶化合物 |
| WO2013113773A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113787A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113716A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113720A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013135672A1 (en) | 2012-03-13 | 2013-09-19 | Basf Se | Fungicidal pyrimidine compounds |
| SG11201608114QA (en) * | 2014-03-28 | 2016-11-29 | Kaneka Corp | Method for producing tri-carbobenzoxy-arginine |
| PL3455216T3 (pl) * | 2016-05-12 | 2021-05-17 | Boehringer Ingelheim International Gmbh | Pochodne pirydynylowe, kompozycje farmaceutyczne i ich zastosowania jako inhibitory aoc3 |
| CN109111376B (zh) * | 2018-09-18 | 2021-09-14 | 四川医立特生物医药有限公司 | 一种2,5-双脱氧链霉胺衍生物及其应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2734904A (en) * | 1956-02-14 | Xcxnhxc-nh | ||
| BE844832A (fr) * | 1976-08-03 | 1977-02-03 | Rorer Inc William H | Nouvelles amidinourees, leur preparation et leur emploi |
| GB8523606D0 (en) * | 1985-09-25 | 1985-10-30 | Shell Int Research | Pesticidal benzoylurea compounds |
| DE3929582A1 (de) * | 1989-09-06 | 1991-03-07 | Hoechst Ag | Benzoylguanidine, verfahren zu ihrer herstellung, ihre verwendung als medikament sowie sie enthaltendes medikament |
| EP0612723B1 (de) * | 1993-02-20 | 1997-08-27 | Hoechst Aktiengesellschaft | Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, als Inhibitoren des zellulären Na+/H+-Austauschs oder als Diagnostikum sowie sie enthaltendes Medikament |
| DE4328869A1 (de) * | 1993-08-27 | 1995-03-02 | Hoechst Ag | Ortho-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
-
1995
- 1995-05-17 DE DE19518073A patent/DE19518073A1/de not_active Withdrawn
-
1996
- 1996-05-13 DK DK96107586T patent/DK0748795T3/da active
- 1996-05-13 SI SI9630255T patent/SI0748795T1/xx unknown
- 1996-05-13 DE DE59605782T patent/DE59605782D1/de not_active Expired - Lifetime
- 1996-05-13 EP EP96107586A patent/EP0748795B1/de not_active Expired - Lifetime
- 1996-05-13 ES ES96107586T patent/ES2149403T3/es not_active Expired - Lifetime
- 1996-05-13 AT AT96107586T patent/ATE195726T1/de not_active IP Right Cessation
- 1996-05-13 PT PT96107586T patent/PT748795E/pt unknown
- 1996-05-15 SK SK629-96A patent/SK282010B6/sk unknown
- 1996-05-15 NO NO962006A patent/NO306156B1/no not_active IP Right Cessation
- 1996-05-15 US US08/648,499 patent/US5753710A/en not_active Expired - Lifetime
- 1996-05-15 TR TR96/00400A patent/TR199600400A2/xx unknown
- 1996-05-15 PL PL96314253A patent/PL183629B1/pl unknown
- 1996-05-15 RU RU96109706/04A patent/RU2188191C2/ru not_active IP Right Cessation
- 1996-05-15 HR HR960221A patent/HRP960221B1/xx not_active IP Right Cessation
- 1996-05-15 IL IL11827896A patent/IL118278A/en not_active IP Right Cessation
- 1996-05-15 AU AU52294/96A patent/AU701567B2/en not_active Ceased
- 1996-05-15 AR ARP960102580A patent/AR002741A1/es not_active Application Discontinuation
- 1996-05-15 NZ NZ286583A patent/NZ286583A/en unknown
- 1996-05-15 CN CN96107454A patent/CN1062555C/zh not_active Expired - Fee Related
- 1996-05-15 CZ CZ19961415A patent/CZ288332B6/cs not_active IP Right Cessation
- 1996-05-16 ZA ZA9603893A patent/ZA963893B/xx unknown
- 1996-05-16 HU HU9601321A patent/HUP9601321A3/hu unknown
- 1996-05-16 KR KR1019960016312A patent/KR960040130A/ko not_active Application Discontinuation
- 1996-05-16 MY MYPI96001851A patent/MY115805A/en unknown
- 1996-05-16 CA CA002176796A patent/CA2176796C/en not_active Expired - Fee Related
- 1996-05-16 JP JP12142196A patent/JP3962110B2/ja not_active Expired - Fee Related
- 1996-05-17 BR BR9602337A patent/BR9602337A/pt active Search and Examination
- 1996-06-14 TW TW085107134A patent/TW355705B/zh active
-
1998
- 1998-01-09 US US09/005,163 patent/US6022899A/en not_active Expired - Lifetime
-
2000
- 2000-10-06 GR GR20000402262T patent/GR3034573T3/el not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |