CA2304849A1 - Bisethers de 1-oxa, aza et thianaphtalene-2-one inhibiteurs du phospholambane - Google Patents
Bisethers de 1-oxa, aza et thianaphtalene-2-one inhibiteurs du phospholambane Download PDFInfo
- Publication number
- CA2304849A1 CA2304849A1 CA002304849A CA2304849A CA2304849A1 CA 2304849 A1 CA2304849 A1 CA 2304849A1 CA 002304849 A CA002304849 A CA 002304849A CA 2304849 A CA2304849 A CA 2304849A CA 2304849 A1 CA2304849 A1 CA 2304849A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- aryl
- arylalkyl
- hydrogen
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 102000005681 phospholamban Human genes 0.000 title abstract description 12
- 108010059929 phospholamban Proteins 0.000 title abstract description 12
- 239000003112 inhibitor Substances 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 39
- 125000003118 aryl group Chemical group 0.000 claims abstract description 37
- 239000001257 hydrogen Substances 0.000 claims abstract description 37
- 150000002148 esters Chemical class 0.000 claims abstract description 19
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 17
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 10
- 125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 9
- 125000002252 acyl group Chemical group 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 206010019280 Heart failures Diseases 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical group 0.000 claims abstract 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 8
- 208000002089 myocardial stunning Diseases 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- MRMBHOCJZVMBJN-UHFFFAOYSA-N 3-benzyl-4-methyl-5,7-bis(2h-tetrazol-5-ylmethoxy)chromen-2-one Chemical compound O=C1OC=2C=C(OCC=3NN=NN=3)C=C(OCC=3NN=NN=3)C=2C(C)=C1CC1=CC=CC=C1 MRMBHOCJZVMBJN-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 239000000047 product Substances 0.000 description 94
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 74
- 238000005160 1H NMR spectroscopy Methods 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 39
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 36
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 32
- 238000002844 melting Methods 0.000 description 32
- 230000008018 melting Effects 0.000 description 32
- 239000000243 solution Substances 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 239000000203 mixture Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 25
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- -1 C1_q Chemical group 0.000 description 17
- 235000019270 ammonium chloride Nutrition 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 238000002474 experimental method Methods 0.000 description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 13
- 239000000872 buffer Substances 0.000 description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 239000005457 ice water Substances 0.000 description 11
- 230000010412 perfusion Effects 0.000 description 11
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 210000002027 skeletal muscle Anatomy 0.000 description 9
- JPYHHZQJCSQRJY-UHFFFAOYSA-N Phloroglucinol Natural products CCC=CCC=CCC=CCC=CCCCCC(=O)C1=C(O)C=C(O)C=C1O JPYHHZQJCSQRJY-UHFFFAOYSA-N 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- QCDYQQDYXPDABM-UHFFFAOYSA-N phloroglucinol Chemical compound OC1=CC(O)=CC(O)=C1 QCDYQQDYXPDABM-UHFFFAOYSA-N 0.000 description 8
- 229960001553 phloroglucinol Drugs 0.000 description 8
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
- 230000002861 ventricular Effects 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 230000003185 calcium uptake Effects 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 5
- 239000004816 latex Substances 0.000 description 5
- 229920000126 latex Polymers 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- DVNOTHMAOBZNRF-UHFFFAOYSA-N 1,3-dibenzyl-5,7-dihydroxy-4-methylquinolin-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(O)=CC(O)=C2C(C)=C1CC1=CC=CC=C1 DVNOTHMAOBZNRF-UHFFFAOYSA-N 0.000 description 4
- WNRGWPVJGDABME-UHFFFAOYSA-N 3,5-Dimethoxyaniline Chemical compound COC1=CC(N)=CC(OC)=C1 WNRGWPVJGDABME-UHFFFAOYSA-N 0.000 description 4
- 241000700199 Cavia porcellus Species 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 230000035488 systolic blood pressure Effects 0.000 description 4
- POSZUTFLHGNLHX-KSBRXOFISA-N tris maleate Chemical compound OCC(N)(CO)CO.OCC(N)(CO)CO.OC(=O)\C=C/C(O)=O POSZUTFLHGNLHX-KSBRXOFISA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- 229910015845 BBr3 Inorganic materials 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 102000004612 Calcium-Transporting ATPases Human genes 0.000 description 3
- 108010017954 Calcium-Transporting ATPases Proteins 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 235000011148 calcium chloride Nutrition 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- QCBXSNFQJIQQLN-UHFFFAOYSA-N 1,3-dibenzyl-4-methyl-5,7-bis(2h-tetrazol-5-ylmethoxy)quinolin-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(OCC=3NN=NN=3)=CC(OCC=3NN=NN=3)=C2C(C)=C1CC1=CC=CC=C1 QCBXSNFQJIQQLN-UHFFFAOYSA-N 0.000 description 2
- NPICNJMUNQWUKH-UHFFFAOYSA-N 3-[[3-benzyl-4-methyl-2-oxo-5-[(5-oxo-1,2,4-oxadiazolidin-3-yl)methoxy]chromen-7-yl]oxymethyl]-1,2,4-oxadiazolidin-5-one Chemical compound O=C1OC=2C=C(OCC3NC(=O)ON3)C=C(OCC3NC(=O)ON3)C=2C(C)=C1CC1=CC=CC=C1 NPICNJMUNQWUKH-UHFFFAOYSA-N 0.000 description 2
- HJCRSNVHQFLLFY-UHFFFAOYSA-N 3-benzyl-4-methyl-5,7-bis[1-(2h-tetrazol-5-yl)ethoxy]chromen-2-one Chemical compound N=1N=NNC=1C(C)OC(C=C1OC(=O)C(CC=2C=CC=CC=2)=C(C)C1=1)=CC=1OC(C)C1=NN=NN1 HJCRSNVHQFLLFY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- OHULVMOXKLLMJR-MSOLQXFVSA-N [(2s,6r)-4-benzoyloxy-2-methoxy-5-oxo-2h-pyran-6-yl]methyl benzoate Chemical compound C([C@H]1O[C@@H](C=C(OC(=O)C=2C=CC=CC=2)C1=O)OC)OC(=O)C1=CC=CC=C1 OHULVMOXKLLMJR-MSOLQXFVSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000005236 alkanoylamino group Chemical group 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 210000005003 heart tissue Anatomy 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 210000005246 left atrium Anatomy 0.000 description 2
- 210000005240 left ventricle Anatomy 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- QAXZWHGWYSJAEI-UHFFFAOYSA-N n,n-dimethylformamide;ethanol Chemical compound CCO.CN(C)C=O QAXZWHGWYSJAEI-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 210000003492 pulmonary vein Anatomy 0.000 description 2
- 210000003625 skull Anatomy 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical class C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- SNDULORIDCAWCM-UHFFFAOYSA-N 1,3-dibenzyl-5,7-dimethoxy-4-methylquinolin-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(OC)=CC(OC)=C2C(C)=C1CC1=CC=CC=C1 SNDULORIDCAWCM-UHFFFAOYSA-N 0.000 description 1
- WHOXXIZKHZBTOB-UHFFFAOYSA-N 1,3-dihydroxy-7,8,9,10-tetrahydrobenzo[c]chromen-6-one Chemical compound C1CCCC2=C1C1=C(O)C=C(O)C=C1OC2=O WHOXXIZKHZBTOB-UHFFFAOYSA-N 0.000 description 1
- HDCLBUVMTQHZQE-UHFFFAOYSA-N 1,3-dihydroxy-7-phenyl-7,8,9,10-tetrahydrobenzo[c]chromen-6-one Chemical compound C1=2C(=O)OC3=CC(O)=CC(O)=C3C=2CCCC1C1=CC=CC=C1 HDCLBUVMTQHZQE-UHFFFAOYSA-N 0.000 description 1
- MHOJTFDLYMLLTN-UHFFFAOYSA-N 1,3-dihydroxy-8-phenyl-7,8,9,10-tetrahydrobenzo[c]chromen-6-one Chemical compound C1C=2C(=O)OC3=CC(O)=CC(O)=C3C=2CCC1C1=CC=CC=C1 MHOJTFDLYMLLTN-UHFFFAOYSA-N 0.000 description 1
- IZXWCDITFDNEBY-UHFFFAOYSA-N 1-(chloromethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCl)C=C1 IZXWCDITFDNEBY-UHFFFAOYSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- ZWMXPNVOJPHGOX-UHFFFAOYSA-N 1-benzyl-3-[(2-fluorophenyl)methyl]-5,7-dimethoxy-4-methylquinolin-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(OC)=CC(OC)=C2C(C)=C1CC1=CC=CC=C1F ZWMXPNVOJPHGOX-UHFFFAOYSA-N 0.000 description 1
- NUSAZZBRTPEAON-UHFFFAOYSA-N 1-benzyl-3-[(4-fluorophenyl)methyl]-5,7-dimethoxy-4-methylquinolin-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(OC)=CC(OC)=C2C(C)=C1CC1=CC=C(F)C=C1 NUSAZZBRTPEAON-UHFFFAOYSA-N 0.000 description 1
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- QJVZAZHBUKOZAZ-UHFFFAOYSA-N ethyl 2-[1,3-dibenzyl-5-(2-ethoxy-2-oxoethoxy)-4-methyl-2-oxoquinolin-7-yl]oxyacetate Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(OCC(=O)OCC)=CC(OCC(=O)OCC)=C2C(C)=C1CC1=CC=CC=C1 QJVZAZHBUKOZAZ-UHFFFAOYSA-N 0.000 description 1
- FGSGHBPKHFDJOP-UHFFFAOYSA-N ethyl 2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCCC1=O FGSGHBPKHFDJOP-UHFFFAOYSA-N 0.000 description 1
- GPRDAMCHHGGJNX-UHFFFAOYSA-N ethyl 3-oxo-2-(2-phenylethyl)butanoate Chemical compound CCOC(=O)C(C(C)=O)CCC1=CC=CC=C1 GPRDAMCHHGGJNX-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 125000006277 halobenzyl group Chemical group 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000001087 myotubule Anatomy 0.000 description 1
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- HHAVHBDPWSUKHZ-UHFFFAOYSA-N propan-2-ol;propan-2-one Chemical compound CC(C)O.CC(C)=O HHAVHBDPWSUKHZ-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002097 psoas muscle Anatomy 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 229930185107 quinolinone Natural products 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 125000001424 substituent group Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000005757 von Pechmann cycloaddition reaction Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- 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
- C07D215/16—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
L'invention porte sur les composés à activité thérapeutique de formules (I) et (II) dans lesquelles R¿1? est hydrogène, alkyle, alcényle, aryle, aryalkyle, hydroxyalkyle, halogenalkyle, alkoxy, COR¿10?, CONR¿10?R¿11?, OR¿10?, S(O)¿m?R¿10?, NR¿10?COR¿11? ou NR¿10?R¿11?, ou R¿10? est hydrogène, alkyle, alcényle, aryle, arylalkyle, hydroxyalkyle, halogénalkyle, alkoxy ou hydroxy et R¿11? est hydrogène, alkyle, aryle, arylalkyle, alkoxy, aryloxy, hydroxy ou acyle, ou si X est NR¿11?, R¿1? peut aussi être carboxylalkyle, R¿6? est hydrogène, alkyle, alkényle, aryle, arylalkyle, R¿2? et R¿7? sont hydrogène, alkyle, aryle, arylalkyle, alcényle, COR¿10?, CONR¿10?R¿11?, halogène, trifluorométhyle, nitro ou cyano, où R¿10? et R¿11? sont comme définis ci-dessus, R¿3? est hydrogène, alkyle, aryle ou arylalkyle, A est alkyle ou alkyle substitué, m est 0-2 et n est 1-3, Y est O, NR11 ou S, où R11 est défini comme ci-dessus, X est O, NR11 ou S, où R11 est défini comme ci-dessus, R¿4?, R¿5?, R¿8? et R¿9? sont indépendamment l'un des groupes (a), (b), (c), (d), (e), (f) et (g) suivants ou si X est NR¿11?, R¿4?, R¿5?, R¿8? et R¿9? peuvent aussi être indépendamment HOOC-, R¿12?OOC-, H¿2?NCO- ou HOHNCO-, où R¿12? est alkyle, arylalkyle ou aryle, et où chacun des résidus aryle défini ci-dessus par lui-même ou en tant que partie d'un autre groupe peut être substitué. L'invention porte également sur les sels et esters pharmacocompatibles desdits composés qui présentent une activité inhibitrice du phospholambane et s'avèrent utiles pour le traitement de l'insuffisance cardiaque.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93711997A | 1997-09-24 | 1997-09-24 | |
| US937,119 | 1997-09-24 | ||
| US99015097A | 1997-12-12 | 1997-12-12 | |
| US990,150 | 1997-12-12 | ||
| US10411498A | 1998-06-25 | 1998-06-25 | |
| US104,114 | 1998-06-25 | ||
| PCT/FI1998/000755 WO1999015523A1 (fr) | 1997-09-24 | 1998-09-24 | Bisethers de 1-oxa, aza et thianaphtalene-2-one inhibiteurs du phospholambane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2304849A1 true CA2304849A1 (fr) | 1999-04-01 |
Family
ID=27379660
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002304849A Abandoned CA2304849A1 (fr) | 1997-09-24 | 1998-09-24 | Bisethers de 1-oxa, aza et thianaphtalene-2-one inhibiteurs du phospholambane |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP1017691A1 (fr) |
| JP (1) | JP2003525838A (fr) |
| KR (1) | KR20010015607A (fr) |
| CN (1) | CN1143857C (fr) |
| AU (1) | AU735729B2 (fr) |
| BR (1) | BR9813216A (fr) |
| CA (1) | CA2304849A1 (fr) |
| EA (1) | EA003084B1 (fr) |
| EE (1) | EE04494B1 (fr) |
| HU (1) | HUP0003647A3 (fr) |
| ID (1) | ID24373A (fr) |
| IL (1) | IL134662A0 (fr) |
| NO (1) | NO20001569L (fr) |
| NZ (1) | NZ503044A (fr) |
| PL (1) | PL339493A1 (fr) |
| SK (1) | SK3902000A3 (fr) |
| TR (1) | TR200000764T2 (fr) |
| WO (1) | WO1999015523A1 (fr) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7026491B2 (en) | 2000-07-21 | 2006-04-11 | Chugai Seiyaku Kabushiki Kaisha | Coumarin derivatives useful as TNFα inhibitors |
| GEP20053675B (en) * | 2001-03-30 | 2005-11-25 | Pfizer Prod Inc | Pyridazinone Aldose Reductase Inhibitors |
| US7572910B2 (en) | 2003-02-20 | 2009-08-11 | Pfizer, Inc. | Pyridazinone aldose reductase inhibitors |
| FR2970964B1 (fr) * | 2011-01-28 | 2013-12-13 | Univ Claude Bernard Lyon | Nouveaux derives d'azacoumarines presentant une activite inhibitrice des pompes mdr |
| KR20260021596A (ko) | 2023-04-05 | 2026-02-13 | 아이오니스 파마수티컬즈, 인코포레이티드 | Pln 발현을 감소시키는 화합물 및 방법 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2543945A1 (de) * | 1975-10-02 | 1977-04-21 | Troponwerke Gmbh & Co Kg | 2-benzopyranonderivate, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| GB8529362D0 (en) * | 1985-11-28 | 1986-01-02 | Pfizer Ltd | Quinolone cardiac stimulants |
| GB8630702D0 (en) * | 1986-12-23 | 1987-02-04 | Wellcome Found | Quinoline compound |
| EP0355583B1 (fr) * | 1988-08-10 | 1995-01-25 | Otsuka Pharmaceutical Co., Ltd. | Agents cardiotoniques |
| CA2022236A1 (fr) * | 1989-07-31 | 1991-02-01 | Hiroaki Yanagisawa | Derives de coumarin, leur preparation et leur utilisation pour le traitement des troubles cerebrovasculaires |
| DE4337906A1 (de) * | 1993-11-08 | 1995-05-11 | Cassella Ag | Verwendung von Cumarinderivaten |
-
1998
- 1998-09-24 CA CA002304849A patent/CA2304849A1/fr not_active Abandoned
- 1998-09-24 HU HU0003647A patent/HUP0003647A3/hu unknown
- 1998-09-24 JP JP2000512828A patent/JP2003525838A/ja active Pending
- 1998-09-24 WO PCT/FI1998/000755 patent/WO1999015523A1/fr not_active Ceased
- 1998-09-24 PL PL98339493A patent/PL339493A1/xx unknown
- 1998-09-24 ID IDW20000564A patent/ID24373A/id unknown
- 1998-09-24 SK SK390-2000A patent/SK3902000A3/sk unknown
- 1998-09-24 EP EP98946482A patent/EP1017691A1/fr not_active Withdrawn
- 1998-09-24 EA EA200000352A patent/EA003084B1/ru not_active IP Right Cessation
- 1998-09-24 TR TR2000/00764T patent/TR200000764T2/xx unknown
- 1998-09-24 KR KR1020007003094A patent/KR20010015607A/ko not_active Ceased
- 1998-09-24 AU AU93508/98A patent/AU735729B2/en not_active Ceased
- 1998-09-24 EE EEP200000179A patent/EE04494B1/xx not_active IP Right Cessation
- 1998-09-24 IL IL13466298A patent/IL134662A0/xx unknown
- 1998-09-24 NZ NZ503044A patent/NZ503044A/en unknown
- 1998-09-24 CN CNB98809438XA patent/CN1143857C/zh not_active Expired - Fee Related
- 1998-09-24 BR BR9813216-4A patent/BR9813216A/pt not_active IP Right Cessation
-
2000
- 2000-03-24 NO NO20001569A patent/NO20001569L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IL134662A0 (en) | 2001-04-30 |
| NZ503044A (en) | 2001-08-31 |
| CN1143857C (zh) | 2004-03-31 |
| AU735729B2 (en) | 2001-07-12 |
| HUP0003647A3 (en) | 2002-12-28 |
| ID24373A (id) | 2000-07-13 |
| KR20010015607A (ko) | 2001-02-26 |
| SK3902000A3 (en) | 2000-12-11 |
| JP2003525838A (ja) | 2003-09-02 |
| BR9813216A (pt) | 2000-08-29 |
| EE200000179A (et) | 2001-04-16 |
| AU9350898A (en) | 1999-04-12 |
| HUP0003647A2 (hu) | 2001-08-28 |
| NO20001569D0 (no) | 2000-03-24 |
| EA200000352A1 (ru) | 2000-10-30 |
| TR200000764T2 (tr) | 2001-03-21 |
| EP1017691A1 (fr) | 2000-07-12 |
| CN1271357A (zh) | 2000-10-25 |
| PL339493A1 (en) | 2000-12-18 |
| WO1999015523A1 (fr) | 1999-04-01 |
| NO20001569L (no) | 2000-03-24 |
| EA003084B1 (ru) | 2002-12-26 |
| EE04494B1 (et) | 2005-06-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |