DE60203623T2 - Substituierte piperazinderivate und ihre verwendung als fettsaüre-oxidationsinhibitoren - Google Patents
Substituierte piperazinderivate und ihre verwendung als fettsaüre-oxidationsinhibitoren Download PDFInfo
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- DE60203623T2 DE60203623T2 DE60203623T DE60203623T DE60203623T2 DE 60203623 T2 DE60203623 T2 DE 60203623T2 DE 60203623 T DE60203623 T DE 60203623T DE 60203623 T DE60203623 T DE 60203623T DE 60203623 T2 DE60203623 T2 DE 60203623T2
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- 238000007254 oxidation reaction Methods 0.000 title claims description 26
- 239000003112 inhibitor Substances 0.000 title claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title description 7
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 248
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 241000124008 Mammalia Species 0.000 claims abstract description 9
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 8
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 6
- 208000010125 myocardial infarction Diseases 0.000 claims abstract description 6
- 206010003130 Arrhythmia supraventricular Diseases 0.000 claims abstract description 5
- 208000007718 Stable Angina Diseases 0.000 claims abstract description 5
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 5
- -1 2-methylbenzo-1,3-thiazol-5-yl Chemical group 0.000 claims description 165
- 125000001072 heteroaryl group Chemical group 0.000 claims description 52
- 238000002360 preparation method Methods 0.000 claims description 50
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 230000003647 oxidation Effects 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 19
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 17
- 239000000194 fatty acid Substances 0.000 claims description 17
- 229930195729 fatty acid Natural products 0.000 claims description 17
- 150000004665 fatty acids Chemical class 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 9
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 201000001068 Prinzmetal angina Diseases 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 210000001519 tissue Anatomy 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 239000011593 sulfur Chemical group 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 208000009325 Variant Angina Pectoris Diseases 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 230000035939 shock Effects 0.000 claims description 3
- 210000002027 skeletal muscle Anatomy 0.000 claims description 3
- 238000002054 transplantation Methods 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- QQKJIZOFAXRQPI-UHFFFAOYSA-N 1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-[4-[[5-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]propan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(N=1)=NOC=1C1=CC=C(C(F)(F)F)C=C1 QQKJIZOFAXRQPI-UHFFFAOYSA-N 0.000 claims description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- DXYYSGDWQCSKKO-UHFFFAOYSA-N 2-methylbenzothiazole Chemical compound C1=CC=C2SC(C)=NC2=C1 DXYYSGDWQCSKKO-UHFFFAOYSA-N 0.000 claims 2
- AICXVAPPRIPRMH-JXFKEZNVSA-N (2s)-1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-[(2s)-2-methyl-4-[[5-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]propan-2-ol Chemical compound C([C@@H](N(CC1)C[C@H](O)COC=2C=C3N=C(C)SC3=CC=2)C)N1CC(N=1)=NOC=1C1=CC=C(C(F)(F)F)C=C1 AICXVAPPRIPRMH-JXFKEZNVSA-N 0.000 claims 1
- PYUAONCDAVXNNW-NRFANRHFSA-N (2s)-1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-[4-[[5-[4-(trifluoromethyl)phenyl]-1,2-oxazol-3-yl]methyl]piperazin-1-yl]propan-2-ol Chemical compound C([C@H](O)COC=1C=C2N=C(SC2=CC=1)C)N(CC1)CCN1CC(=NO1)C=C1C1=CC=C(C(F)(F)F)C=C1 PYUAONCDAVXNNW-NRFANRHFSA-N 0.000 claims 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims 1
- WYDWTECDFUFLJT-UHFFFAOYSA-N 1-[4-[[5-(4-chlorophenyl)-1,2-oxazol-3-yl]methyl]piperazin-1-yl]-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(=NO1)C=C1C1=CC=C(Cl)C=C1 WYDWTECDFUFLJT-UHFFFAOYSA-N 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 26
- 206010022562 Intermittent claudication Diseases 0.000 abstract description 4
- 230000001746 atrial effect Effects 0.000 abstract description 4
- 208000021156 intermittent vascular claudication Diseases 0.000 abstract description 4
- 206010002388 Angina unstable Diseases 0.000 abstract description 2
- 208000007814 Unstable Angina Diseases 0.000 abstract description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 abstract description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 abstract 1
- 230000036470 plasma concentration Effects 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 description 74
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
- 239000000203 mixture Substances 0.000 description 64
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- 125000001424 substituent group Chemical group 0.000 description 51
- 125000003118 aryl group Chemical group 0.000 description 47
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 41
- 239000002904 solvent Substances 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 230000002829 reductive effect Effects 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 38
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 37
- 125000003545 alkoxy group Chemical group 0.000 description 33
- 238000000034 method Methods 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 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 28
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 28
- 125000004181 carboxyalkyl group Chemical group 0.000 description 28
- 229910052736 halogen Inorganic materials 0.000 description 27
- 150000002367 halogens Chemical class 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000004480 active ingredient Substances 0.000 description 26
- 239000008103 glucose Substances 0.000 description 26
- 125000003342 alkenyl group Chemical group 0.000 description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 24
- 125000004093 cyano group Chemical group *C#N 0.000 description 24
- 125000000753 cycloalkyl group Chemical group 0.000 description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
- 239000000047 product Substances 0.000 description 23
- 125000000392 cycloalkenyl group Chemical group 0.000 description 21
- 239000003826 tablet Substances 0.000 description 21
- 239000012442 inert solvent Substances 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 210000002216 heart Anatomy 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 125000000304 alkynyl group Chemical group 0.000 description 16
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 15
- 150000003839 salts Chemical class 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 230000010412 perfusion Effects 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- YBJJKPOQWUEERM-UHFFFAOYSA-N 1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-piperazin-1-ylpropan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN1CCNCC1 YBJJKPOQWUEERM-UHFFFAOYSA-N 0.000 description 12
- 125000002252 acyl group Chemical group 0.000 description 12
- 125000004442 acylamino group Chemical group 0.000 description 12
- 125000004423 acyloxy group Chemical group 0.000 description 12
- 125000004414 alkyl thio group Chemical group 0.000 description 12
- 125000005110 aryl thio group Chemical group 0.000 description 12
- 125000004104 aryloxy group Chemical group 0.000 description 12
- 125000005553 heteroaryloxy group Chemical group 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 125000003396 thiol group Chemical group [H]S* 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 125000000033 alkoxyamino group Chemical group 0.000 description 11
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 11
- 125000005368 heteroarylthio group Chemical group 0.000 description 11
- 125000004468 heterocyclylthio group Chemical group 0.000 description 11
- 125000000547 substituted alkyl group Chemical group 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 229930194542 Keto Chemical group 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 10
- 125000000468 ketone group Chemical group 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- 125000006598 aminocarbonylamino group Chemical group 0.000 description 9
- 150000001540 azides Chemical group 0.000 description 9
- 230000034659 glycolysis Effects 0.000 description 9
- 125000004470 heterocyclooxy group Chemical group 0.000 description 9
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000003963 antioxidant agent Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- XCARGDPHZYJCMU-UHFFFAOYSA-N 2-chloro-n'-hydroxyethanimidamide Chemical compound ClCC(N)=NO XCARGDPHZYJCMU-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 150000007530 organic bases Chemical class 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- LAKVUPMDDFICNR-UHFFFAOYSA-N 2-methyl-1,3-benzothiazol-5-ol Chemical compound OC1=CC=C2SC(C)=NC2=C1 LAKVUPMDDFICNR-UHFFFAOYSA-N 0.000 description 5
- IPCSVZSSVZVIGE-BFDQMJDGSA-N 5-tritiohexadecanoic acid Chemical compound C(CCCC(CCCCCCCCCCC)[3H])(=O)O IPCSVZSSVZVIGE-BFDQMJDGSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 230000003078 antioxidant effect Effects 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 210000004165 myocardium Anatomy 0.000 description 5
- 150000004885 piperazines Chemical class 0.000 description 5
- 230000036316 preload Effects 0.000 description 5
- 125000005017 substituted alkenyl group Chemical group 0.000 description 5
- 125000005156 substituted alkylene group Chemical group 0.000 description 5
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 5
- OHIMGDQOEPFSSL-UHFFFAOYSA-N 1-(2-chloroethyl)-4-(4-fluorophenyl)pyrazole Chemical compound C1=CC(F)=CC=C1C1=CN(CCCl)N=C1 OHIMGDQOEPFSSL-UHFFFAOYSA-N 0.000 description 4
- YSPRCDGVFRVBED-UHFFFAOYSA-N 2-methyl-5-(oxiran-2-ylmethoxy)-1,3-benzothiazole Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC1CO1 YSPRCDGVFRVBED-UHFFFAOYSA-N 0.000 description 4
- YCOKTYBAJSXBTK-UHFFFAOYSA-N 3-(chloromethyl)-5-(3-fluorophenyl)-1,2,4-oxadiazole Chemical compound FC1=CC=CC(C=2ON=C(CCl)N=2)=C1 YCOKTYBAJSXBTK-UHFFFAOYSA-N 0.000 description 4
- FOPHIEABULMTDJ-UHFFFAOYSA-N 3-(chloromethyl)-5-[4-(trifluoromethyl)phenyl]-1,2-oxazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC(CCl)=NO1 FOPHIEABULMTDJ-UHFFFAOYSA-N 0.000 description 4
- OFVIHHHWOQCWEK-UHFFFAOYSA-N 5-(chloromethyl)-3-(3-fluorophenyl)-1,2,4-oxadiazole Chemical compound FC1=CC=CC(C=2N=C(CCl)ON=2)=C1 OFVIHHHWOQCWEK-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- XKLMZUWKNUAPSZ-UHFFFAOYSA-N N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide Chemical compound COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC=2C(=CC=CC=2C)C)CC1 XKLMZUWKNUAPSZ-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- HTDMXATWYNKLLE-UHFFFAOYSA-N [5-[4-(trifluoromethyl)phenyl]-1,2-oxazol-3-yl]methanol Chemical compound O1N=C(CO)C=C1C1=CC=C(C(F)(F)F)C=C1 HTDMXATWYNKLLE-UHFFFAOYSA-N 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000011067 equilibration Methods 0.000 description 4
- MKMLEMDGZCVWJB-UHFFFAOYSA-N ethyl 5-[4-(trifluoromethyl)phenyl]-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OCC)C=C1C1=CC=C(C(F)(F)F)C=C1 MKMLEMDGZCVWJB-UHFFFAOYSA-N 0.000 description 4
- WWWSJJPBJGEKKY-UHFFFAOYSA-N ethyl 5-[4-(trifluoromethyl)phenyl]-4,5-dihydro-1,2-oxazole-3-carboxylate Chemical compound C1C(C(=O)OCC)=NOC1C1=CC=C(C(F)(F)F)C=C1 WWWSJJPBJGEKKY-UHFFFAOYSA-N 0.000 description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 4
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- AUIXBRCHZDSKLC-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-3-[(2-phenyl-3h-benzimidazol-5-yl)oxy]propyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)COC1=CC=C(N=C(N2)C=3C=CC=CC=3)C2=C1 AUIXBRCHZDSKLC-UHFFFAOYSA-N 0.000 description 1
- IENFLFSMBDWJRG-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-4-(2-methoxyphenoxy)butyl]piperazine-1-carboxylate Chemical compound COC1=CC=CC=C1OCCC(O)CN1CCN(C(=O)OC(C)(C)C)CC1 IENFLFSMBDWJRG-UHFFFAOYSA-N 0.000 description 1
- CMXUXPHYDAUYBY-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-4-[(2-methyl-1,3-benzothiazol-5-yl)oxy]butyl]piperazine-1-carboxylate Chemical compound C=1C=C2SC(C)=NC2=CC=1OCCC(O)CN1CCN(C(=O)OC(C)(C)C)CC1 CMXUXPHYDAUYBY-UHFFFAOYSA-N 0.000 description 1
- MZYKRTRAZWZLBH-UHFFFAOYSA-N tert-butyl 4-[3-(1-fluoronaphthalen-2-yl)oxy-2-hydroxypropyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)COC1=CC=C(C=CC=C2)C2=C1F MZYKRTRAZWZLBH-UHFFFAOYSA-N 0.000 description 1
- KYAKKAMGAAUBFZ-UHFFFAOYSA-N tert-butyl 4-[3-(8-fluoronaphthalen-1-yl)oxy-2-hydroxypropyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)COC1=CC=CC2=CC=CC(F)=C12 KYAKKAMGAAUBFZ-UHFFFAOYSA-N 0.000 description 1
- SHNPJRUSVXSHHY-UHFFFAOYSA-N tert-butyl 4-[3-[(2-ethyl-1,3-thiazol-4-yl)oxy]-2-hydroxypropyl]piperazine-1-carboxylate Chemical compound S1C(CC)=NC(OCC(O)CN2CCN(CC2)C(=O)OC(C)(C)C)=C1 SHNPJRUSVXSHHY-UHFFFAOYSA-N 0.000 description 1
- DCZJYNHYQRCTDU-UHFFFAOYSA-N tert-butyl 4-[4-(2-fluorophenoxy)-2-hydroxybutyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)CCOC1=CC=CC=C1F DCZJYNHYQRCTDU-UHFFFAOYSA-N 0.000 description 1
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- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000005259 triarylamine group Chemical group 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 229910052905 tridymite Inorganic materials 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
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
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- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
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- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07D277/62—Benzothiazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- 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
- C07D417/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
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- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Lubricants (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
- Paper (AREA)
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| US30662101P | 2001-07-19 | 2001-07-19 | |
| US306621P | 2001-07-19 | ||
| PCT/US2002/022897 WO2003008411A1 (en) | 2001-07-19 | 2002-07-18 | Substituted piperazine compounds and their use as fatty acid oxidation inhibitors |
Publications (2)
| Publication Number | Publication Date |
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| DE60203623D1 DE60203623D1 (de) | 2005-05-12 |
| DE60203623T2 true DE60203623T2 (de) | 2006-01-19 |
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| AU2003248558B8 (en) * | 2002-05-21 | 2009-07-09 | Gilead Sciences, Inc. | Method of treating diabetes |
| US8822473B2 (en) * | 2002-05-21 | 2014-09-02 | Gilead Sciences, Inc. | Method of treating diabetes |
| WO2004014881A2 (en) | 2002-08-09 | 2004-02-19 | Astra Zeneca Ab | '1,2,4'oxadiazoles as modulators of metabotropic glutamate receptor-5 |
| CN1691944A (zh) * | 2002-08-09 | 2005-11-02 | 阿斯利康(瑞典)有限公司 | 作为代谢型谷氨酸受体－5调节剂的噁二唑 |
| AU2003264018A1 (en) | 2002-08-09 | 2004-02-25 | Astrazeneca Ab | Compounds having an activity at metabotropic glutamate receptors |
| ATE365737T1 (de) * | 2002-12-05 | 2007-07-15 | Cv Therapeutics Inc | Substituierte piperazinverbindungen undderen verwendung als fettsuureoxidationsinhibitoren |
| EP1806346B1 (en) * | 2002-12-05 | 2009-07-22 | Cv Therapeutics, Inc. | Substituted piperazine compounds and their use as fatty acid oxidation inhibitors |
| NZ541069A (en) | 2003-01-03 | 2008-09-26 | Cv Therapeutics Inc | Piperazine derivatives as fatty acid oxidation inhibitors |
| WO2004069818A1 (en) * | 2003-01-17 | 2004-08-19 | Cv Therapeutics Inc. | Substituted heterocyclic compounds useful in the treatment of cardiovascular diseases |
| CA2530376A1 (en) * | 2003-06-23 | 2005-01-06 | Cv Therapeutics, Inc. | Urea derivatives of piperazines and piperidines as fatty acid oxidation inhibitors |
| CA2550257A1 (en) | 2003-12-18 | 2005-07-07 | Cv Therapeutics, Inc. | 1-akan-2-ol substituted piperazine and piperidine compounds |
| JP2007517550A (ja) | 2004-01-02 | 2007-07-05 | アドヴァンスド カーディオヴァスキュラー システムズ， インコーポレイテッド | 高比重リポ蛋白をコーティングした医療デバイス |
| US7271169B2 (en) * | 2004-09-08 | 2007-09-18 | Cv Therapeutics, Inc. | Substituted heterocyclic compounds |
| CN101541331A (zh) | 2006-08-24 | 2009-09-23 | 沃克哈特研究中心 | 具有抗微生物活性的新颖大环内酯和酮内酯 |
| US8088920B2 (en) * | 2008-03-31 | 2012-01-03 | Hoffmann-La Roche Inc. | 3-trifluoromethyl-pyrazine-2-carboxylic acid amide derivatives as HDL-cholesterol raising agents |
| ES2617873T3 (es) * | 2008-10-10 | 2017-06-20 | Vm Discovery, Inc. | Composiciones y métodos para tratar trastornos de alcoholismo, dolor y otras enfermedades |
| MX2011012140A (es) * | 2009-05-14 | 2012-02-28 | Gilead Sciences Inc | Ranolazina para el tratamiento de problemas del snc. |
| WO2011115150A1 (ja) * | 2010-03-18 | 2011-09-22 | 興和株式会社 | ベンゾチアジン化合物の製造方法 |
| CN111285819A (zh) * | 2018-12-07 | 2020-06-16 | 江苏恩华药业股份有限公司 | 一种苯并噁唑类化合物及其应用 |
| WO2023023995A1 (zh) * | 2021-08-25 | 2023-03-02 | 苏州大学 | 一种防治心肌缺血后心功能衰竭的药物及其应用 |
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| GB1133989A (en) * | 1964-12-08 | 1968-11-20 | Chugai Pharmaceutical Co Ltd | Theophylline derivatives, their salts and process for preparing the same |
| DE2834114A1 (de) * | 1978-08-01 | 1980-02-14 | Schering Ag | Polyalkoxyphenylpyrrolidone iii, verfahren zu ihrer herstellung und ihre verwendung |
| US4567264A (en) * | 1983-05-18 | 1986-01-28 | Syntex (U.S.A.) Inc. | Cardioselective aryloxy- and arylthio- hydroxypropylene-piperazinyl acetanilides which affect calcium entry |
| JPS6137765A (ja) * | 1984-07-19 | 1986-02-22 | サンド・アクチエンゲゼルシヤフト | ３‐アミノプロポキシアリール誘導体 |
| US4723014A (en) * | 1986-11-19 | 1988-02-02 | Warner-Lambert Company | Process for the preparation of 2-substituted-1,4-dihydropyridines |
| DE3723648A1 (de) * | 1987-07-17 | 1989-01-26 | Sandoz Ag | Indol-derivate, ihre herstellung und sie enthaltende arzneimittel |
| JPH0699399B2 (ja) * | 1988-10-06 | 1994-12-07 | 三井東圧化学株式会社 | 新規複素環化合物およびそれを有効成分として含有する製癌剤効果増強剤 |
| JPH02268162A (ja) * | 1989-04-10 | 1990-11-01 | Fujisawa Pharmaceut Co Ltd | ジフェニルピリジン誘導体 |
| MX9308025A (es) * | 1992-12-22 | 1994-08-31 | Lilly Co Eli | Compuestos inhibidores de la proteasa del virus dela inmunodeficiencia humana, procedimiento para supreparacion y formulacion farmaceutica que los contiene. |
| EP0938480A1 (en) * | 1996-11-14 | 1999-09-01 | American Home Products Corporation | Substituted tetrahydro-1,3,5-triazin-2 1h]-thiones as anti-atherosclerotic agents |
| BR0013943A (pt) * | 1999-09-13 | 2002-05-14 | American Home Prod | Conjugados de glicopiranosìdeos de 2-(4-hidróxi-fenil)-1-[4-(2-amin-1-il-etóxi)-benzil]-1h-indo l-5-óis |
| SE9904765D0 (sv) * | 1999-12-23 | 1999-12-23 | Astra Ab | Pharmaceutically-useful compounds |
| WO2001062711A2 (en) * | 2000-02-22 | 2001-08-30 | Cv Therapeutics, Inc. | Substituted alkylene diamine compounds |
| AU2001238590A1 (en) * | 2000-02-22 | 2001-09-03 | Cv Therapeutics, Inc. | Substituted piperazine compounds |
| US6451798B2 (en) * | 2000-02-22 | 2002-09-17 | Cv Therapeutics, Inc. | Substituted alkyl piperazine derivatives |
| US6552023B2 (en) * | 2000-02-22 | 2003-04-22 | Cv Therapeutics, Inc. | Aralkyl substituted piperazine compounds |
| NZ520782A (en) * | 2000-02-22 | 2004-03-26 | Cv Therapeutics Inc | Substituted piperazine compounds that are partial fatty acid oxidation inhibitors |
| SE0003795D0 (sv) * | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Pharmaceutically useful compounds |
| US6573264B1 (en) * | 2000-10-23 | 2003-06-03 | Cv Therapeutics, Inc. | Heteroaryl alkyl piperazine derivatives |
-
2002
- 2002-07-18 MX MXPA04000565A patent/MXPA04000565A/es active IP Right Grant
- 2002-07-18 EP EP02756522A patent/EP1406898B1/en not_active Expired - Lifetime
- 2002-07-18 KR KR1020047000898A patent/KR100919141B1/ko not_active Expired - Fee Related
- 2002-07-18 DK DK02756522T patent/DK1406898T3/da active
- 2002-07-18 NZ NZ530705A patent/NZ530705A/en not_active IP Right Cessation
- 2002-07-18 WO PCT/US2002/022897 patent/WO2003008411A1/en not_active Ceased
- 2002-07-18 HU HU0402088A patent/HUP0402088A3/hu unknown
- 2002-07-18 PT PT02756522T patent/PT1406898E/pt unknown
- 2002-07-18 DE DE60203623T patent/DE60203623T2/de not_active Expired - Fee Related
- 2002-07-18 CN CNA02814371XA patent/CN1533388A/zh active Pending
- 2002-07-18 PL PL02368529A patent/PL368529A1/xx not_active Application Discontinuation
- 2002-07-18 CA CA002454059A patent/CA2454059A1/en not_active Abandoned
- 2002-07-18 ES ES02756522T patent/ES2236557T3/es not_active Expired - Lifetime
- 2002-07-18 IL IL15989702A patent/IL159897A0/xx unknown
- 2002-07-18 RU RU2004104951/04A patent/RU2300533C2/ru not_active IP Right Cessation
- 2002-07-18 AT AT02756522T patent/ATE292633T1/de not_active IP Right Cessation
- 2002-07-18 US US10/198,237 patent/US6930111B2/en not_active Expired - Fee Related
- 2002-07-18 JP JP2003513970A patent/JP2004537554A/ja not_active Ceased
-
2004
- 2004-01-19 NO NO20040234A patent/NO327635B1/no not_active IP Right Cessation
- 2004-01-19 ZA ZA200400404A patent/ZA200400404B/en unknown
-
2008
- 2008-07-03 AU AU2008202958A patent/AU2008202958A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1406898B1 (en) | 2005-04-06 |
| WO2003008411A1 (en) | 2003-01-30 |
| NO327635B1 (no) | 2009-09-07 |
| EP1406898A1 (en) | 2004-04-14 |
| NO20040234L (no) | 2004-03-18 |
| US6930111B2 (en) | 2005-08-16 |
| DK1406898T3 (da) | 2005-05-30 |
| IL159897A0 (en) | 2004-06-20 |
| DE60203623D1 (de) | 2005-05-12 |
| RU2300533C2 (ru) | 2007-06-10 |
| CN1533388A (zh) | 2004-09-29 |
| CA2454059A1 (en) | 2003-01-30 |
| MXPA04000565A (es) | 2005-06-17 |
| AU2008202958A1 (en) | 2008-07-31 |
| AU2002322527A2 (en) | 2003-03-03 |
| PL368529A1 (en) | 2005-04-04 |
| AU2002322527B2 (en) | 2008-04-17 |
| NZ530705A (en) | 2005-08-26 |
| HUP0402088A2 (hu) | 2005-02-28 |
| ES2236557T3 (es) | 2005-07-16 |
| US20030181352A1 (en) | 2003-09-25 |
| KR20040029374A (ko) | 2004-04-06 |
| RU2004104951A (ru) | 2005-06-27 |
| HUP0402088A3 (en) | 2010-03-29 |
| HK1064374A1 (en) | 2005-01-28 |
| KR100919141B1 (ko) | 2009-09-25 |
| PT1406898E (pt) | 2005-08-31 |
| ATE292633T1 (de) | 2005-04-15 |
| JP2004537554A (ja) | 2004-12-16 |
| ZA200400404B (en) | 2004-10-14 |
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| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |