SK286256B6 - Biarylové deriváty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents
Biarylové deriváty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK286256B6 SK286256B6 SK1908-2000A SK19082000A SK286256B6 SK 286256 B6 SK286256 B6 SK 286256B6 SK 19082000 A SK19082000 A SK 19082000A SK 286256 B6 SK286256 B6 SK 286256B6
- Authority
- SK
- Slovakia
- Prior art keywords
- amino
- ethyl
- biphenyl
- chlorophenyl
- hydroxyethyl
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims abstract description 115
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 29
- 230000008569 process Effects 0.000 title claims abstract description 7
- 125000005841 biaryl group Chemical class 0.000 title abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 208
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 111
- 239000000543 intermediate Substances 0.000 claims description 95
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 66
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 58
- -1 nitro, cyano, hydroxymethyl Chemical group 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 239000004480 active ingredient Substances 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 150000005347 biaryls Chemical class 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- HHFHHEFKHJOXBW-QFIPXVFZSA-N (1r)-1-(3-chlorophenyl)-2-[2-(3-phenylanilino)ethylamino]ethanol Chemical compound C([C@H](O)C=1C=C(Cl)C=CC=1)NCCNC(C=1)=CC=CC=1C1=CC=CC=C1 HHFHHEFKHJOXBW-QFIPXVFZSA-N 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 19
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 150000004702 methyl esters Chemical class 0.000 claims description 11
- 229960003512 nicotinic acid Drugs 0.000 claims description 11
- 239000011664 nicotinic acid Substances 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 239000004305 biphenyl Substances 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 235000010290 biphenyl Nutrition 0.000 claims description 7
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- YMRIDJQAEZFTSC-UHFFFAOYSA-N 2,3-dihydro-1h-tetrazole Chemical compound N1NC=NN1 YMRIDJQAEZFTSC-UHFFFAOYSA-N 0.000 claims description 4
- BAPUQSSJZHLNHK-QFIPXVFZSA-N 3-[3-[2-[[(2r)-2-(3,5-dichlorophenyl)-2-hydroxyethyl]amino]ethylamino]phenyl]benzoic acid Chemical compound C([C@H](O)C=1C=C(Cl)C=C(Cl)C=1)NCCNC(C=1)=CC=CC=1C1=CC=CC(C(O)=O)=C1 BAPUQSSJZHLNHK-QFIPXVFZSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical compound NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 claims description 3
- DOGXHKMRIIVWNP-QFIPXVFZSA-N 4-[3-[2-[[(2r)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethylamino]phenyl]phthalic acid Chemical compound C([C@H](O)C=1C=C(Cl)C=CC=1)NCCNC(C=1)=CC=CC=1C1=CC=C(C(O)=O)C(C(O)=O)=C1 DOGXHKMRIIVWNP-QFIPXVFZSA-N 0.000 claims description 3
- UOTZJBMSOVLQAQ-NRFANRHFSA-N 5-[3-[2-[[(2r)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethylamino]phenyl]pyridine-3-carboxylic acid Chemical compound C([C@H](O)C=1C=C(Cl)C=CC=1)NCCNC(C=1)=CC=CC=1C1=CN=CC(C(O)=O)=C1 UOTZJBMSOVLQAQ-NRFANRHFSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000011737 fluorine Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- 206010046543 Urinary incontinence Diseases 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- AFXVNMWMSXRKBE-QHCPKHFHSA-N methyl 3-[3-[2-[[(2r)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethylamino]phenyl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2C=C(NCCNC[C@H](O)C=3C=C(Cl)C=CC=3)C=CC=2)=C1 AFXVNMWMSXRKBE-QHCPKHFHSA-N 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 8
- 239000000808 adrenergic beta-agonist Substances 0.000 claims 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 2
- 229910052794 bromium Inorganic materials 0.000 claims 2
- INXPJVQGSMHBDG-QHCPKHFHSA-N 4-[3-[2-[[(2r)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethylamino]phenyl]-3-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC(C(O)=O)=CC=C1C1=CC=CC(NCCNC[C@H](O)C=2C=C(Cl)C=CC=2)=C1 INXPJVQGSMHBDG-QHCPKHFHSA-N 0.000 claims 1
- BGFUXHUMITWARX-MWTRTKDXSA-N 4-[3-[[(2r)-2-[[(2r)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]amino]phenyl]benzoic acid Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(Cl)C=CC=1)NC(C=1)=CC=CC=1C1=CC=C(C(O)=O)C=C1 BGFUXHUMITWARX-MWTRTKDXSA-N 0.000 claims 1
- 102100034159 Beta-3 adrenergic receptor Human genes 0.000 abstract 1
- 239000000048 adrenergic agonist Substances 0.000 abstract 1
- 108040005346 beta3-adrenergic receptor activity proteins Proteins 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000000243 solution Substances 0.000 description 79
- 239000007787 solid Substances 0.000 description 64
- 239000000203 mixture Substances 0.000 description 62
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 61
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
- 239000011541 reaction mixture Substances 0.000 description 56
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 55
- 238000004949 mass spectrometry Methods 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- 229910001868 water Inorganic materials 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 150000002500 ions Chemical class 0.000 description 29
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 29
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 29
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 28
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 26
- 102000005962 receptors Human genes 0.000 description 25
- 108020003175 receptors Proteins 0.000 description 25
- 239000008346 aqueous phase Substances 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000012074 organic phase Substances 0.000 description 22
- 238000000926 separation method Methods 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 239000003480 eluent Substances 0.000 description 19
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 18
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 18
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 description 18
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 239000003826 tablet Substances 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 239000006260 foam Substances 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- 239000000556 agonist Substances 0.000 description 15
- 239000002775 capsule Substances 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- ZNRGSYUVFVNSAW-UHFFFAOYSA-N 3-nitrophenylboronic acid Chemical compound OB(O)C1=CC=CC([N+]([O-])=O)=C1 ZNRGSYUVFVNSAW-UHFFFAOYSA-N 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- 238000002156 mixing Methods 0.000 description 12
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
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- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000000908 ammonium hydroxide Substances 0.000 description 8
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 8
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000013270 controlled release Methods 0.000 description 8
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 7
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- 239000004014 plasticizer Substances 0.000 description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 7
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- 239000000377 silicon dioxide Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 6
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
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- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 6
- FYRPEHRWMVMHQM-UHFFFAOYSA-N 1-nitro-3-phenylbenzene Chemical compound [O-][N+](=O)C1=CC=CC(C=2C=CC=CC=2)=C1 FYRPEHRWMVMHQM-UHFFFAOYSA-N 0.000 description 5
- 229920003136 Eudragit® L polymer Polymers 0.000 description 5
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- 239000002585 base Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 5
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- GIISOKXJNMYXHH-SFHVURJKSA-N tert-butyl n-[(2r)-2-[tert-butyl(dimethyl)silyl]oxy-2-(3-chlorophenyl)ethyl]-n-(2-oxoethyl)carbamate Chemical compound CC(C)(C)OC(=O)N(CC=O)C[C@H](O[Si](C)(C)C(C)(C)C)C1=CC=CC(Cl)=C1 GIISOKXJNMYXHH-SFHVURJKSA-N 0.000 description 5
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 238000010792 warming Methods 0.000 description 5
- MUNOBADFTHUUFG-UHFFFAOYSA-N 3-phenylaniline Chemical compound NC1=CC=CC(C=2C=CC=CC=2)=C1 MUNOBADFTHUUFG-UHFFFAOYSA-N 0.000 description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
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- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
- 239000012346 acetyl chloride Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
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Classifications
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- 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
- C07D213/60—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 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
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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
- C07D213/60—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 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Neurology (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9812709.5A GB9812709D0 (en) | 1998-06-13 | 1998-06-13 | Chemical compounds |
| PCT/EP1999/003958 WO1999065877A1 (en) | 1998-06-13 | 1999-06-09 | Therapeutic biaryl derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK19082000A3 SK19082000A3 (sk) | 2001-09-11 |
| SK286256B6 true SK286256B6 (sk) | 2008-06-06 |
Family
ID=10833658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1908-2000A SK286256B6 (sk) | 1998-06-13 | 1999-06-09 | Biarylové deriváty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie |
Country Status (37)
| Country | Link |
|---|---|
| US (1) | US6251925B1 (cs) |
| EP (1) | EP1087943B1 (cs) |
| JP (1) | JP3471754B2 (cs) |
| KR (1) | KR100415877B1 (cs) |
| CN (1) | CN1214008C (cs) |
| AP (1) | AP1687A (cs) |
| AR (1) | AR029301A1 (cs) |
| AT (1) | ATE302189T1 (cs) |
| AU (1) | AU753004B2 (cs) |
| BR (1) | BR9911182B1 (cs) |
| CA (1) | CA2334713C (cs) |
| CO (1) | CO5060482A1 (cs) |
| CZ (1) | CZ299172B6 (cs) |
| DE (1) | DE69926752T2 (cs) |
| DK (1) | DK1087943T3 (cs) |
| EA (1) | EA003641B1 (cs) |
| EE (1) | EE04435B1 (cs) |
| EG (1) | EG23856A (cs) |
| ES (1) | ES2245107T3 (cs) |
| GB (1) | GB9812709D0 (cs) |
| HR (1) | HRP20000854B1 (cs) |
| HU (1) | HUP0102668A3 (cs) |
| ID (1) | ID27841A (cs) |
| IL (2) | IL140219A0 (cs) |
| IS (1) | IS2277B (cs) |
| MY (1) | MY119542A (cs) |
| NO (1) | NO318782B1 (cs) |
| NZ (1) | NZ508805A (cs) |
| PE (1) | PE20000726A1 (cs) |
| PL (1) | PL196943B1 (cs) |
| RS (1) | RS49921B (cs) |
| SI (1) | SI1087943T1 (cs) |
| SK (1) | SK286256B6 (cs) |
| TR (1) | TR200100299T2 (cs) |
| TW (1) | TWI244471B (cs) |
| WO (1) | WO1999065877A1 (cs) |
| ZA (1) | ZA200007417B (cs) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9929118D0 (en) * | 1999-12-10 | 2000-02-02 | Glaxo Group Ltd | Chemical compounds |
| GB9929297D0 (en) * | 1999-12-11 | 2000-02-02 | Glaxo Group Ltd | Process |
| DE10005150A1 (de) * | 2000-02-07 | 2001-08-09 | Merck Patent Gmbh | Verfahren zur Herstellung von 5-Arylnicotinaldehyden |
| CN1469876A (zh) | 2000-10-20 | 2004-01-21 | �Ʒ� | α-芳基乙醇胺及其用作β-3肾上腺素能受体激动剂的用途 |
| AR035605A1 (es) | 2000-12-11 | 2004-06-16 | Bayer Corp | Derivados de aminometil cromano di-sustituidos, un metodo para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la manufactura de medicamentos utiles como agonistas beta-3-adreno-receptores |
| GB0102407D0 (en) | 2001-01-31 | 2001-03-14 | Glaxo Group Ltd | Process |
| US7034053B2 (en) | 2001-01-31 | 2006-04-25 | Smithkline Beecham Corporation | Phenethanolamine derivatives, compositions, and their use as agonists at atypical beta-adrenoreceptors |
| US7709677B2 (en) | 2001-01-31 | 2010-05-04 | Glaxosmithkline Llc | Process of preparing arylethanoldiamines |
| GB0102408D0 (en) * | 2001-01-31 | 2001-03-14 | Glaxo Group Ltd | Chemical compounds |
| EP1236723A1 (en) * | 2001-03-01 | 2002-09-04 | Pfizer Products Inc. | Sulfamide derivatives useful as beta3 agonists and pharmaceutical uses thereof |
| AR035858A1 (es) | 2001-04-23 | 2004-07-21 | Bayer Corp | Derivados de cromano 2,6-sustituidos,composiciones farmaceuticas,uso de dichos derivados para la manufactura de medicamentos utiles como agonistas adrenorreceptores beta-3 |
| WO2003024948A1 (en) | 2001-09-14 | 2003-03-27 | Bayer Pharmaceuticals Corporation | Benzofuran and dihydrobenzofuran derivatives useful as beta-3 adrenoreceptor agonists |
| AU2003209527A1 (en) | 2002-02-27 | 2003-09-09 | Pfizer Products Inc. | Crystal forms of (r)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol |
| AU2003248352A1 (en) | 2002-02-27 | 2003-09-09 | Pfizer Products Inc. | PROCESSES AND INTERMEDIATES USEFUL IN PREPARING Beta3-ADRENERGIC RECEPTOR AGONISTS |
| DOP2003000587A (es) * | 2002-02-27 | 2003-08-30 | Pfizer Prod Inc | AGONISTAS DEL RECEPTOR ß3-ADRENERGICO |
| WO2003072571A1 (en) * | 2002-02-27 | 2003-09-04 | Pfizer Products Inc. | Salt of a pyridyl ethanolamine derivative and its use as a beta-3-adrenergic receptor agonist |
| US6864268B2 (en) | 2002-02-27 | 2005-03-08 | Pfizer Inc. | β3 adrenergic receptor agonists |
| MXPA05000663A (es) * | 2002-07-17 | 2005-09-20 | Lek Pharmaceuticals | Derivados novedosos de piridiletanol (feniletil) aminas como inhibidores de la biosintesis de colesterol, proceso para su preparacion, y composiciones farmaceuticas que los contienen. |
| GB0220730D0 (en) * | 2002-09-06 | 2002-10-16 | Glaxo Group Ltd | Medicinal compounds |
| SI1569907T1 (sl) * | 2002-12-13 | 2016-06-30 | Ym Biosciences Australia Pty Ltd | Na nikotinamidu osnovani kinazni inhibitorji |
| EP1593666B1 (en) * | 2003-02-14 | 2008-07-02 | Kissei Pharmaceutical Co., Ltd. | Amino alcohol derivatives, pharmaceutical compositions containing the same, and use thereof |
| CN100418944C (zh) * | 2003-02-14 | 2008-09-17 | 橘生药品工业株式会社 | 氨基醇衍生物、含有所述氨基醇衍生物的药物组合物及其应用 |
| EP1679304A4 (en) | 2003-10-24 | 2006-11-15 | Kissei Pharmaceutical | AMINO ALCOHOL DERIVATIVE, MEDICAL COMPOSITION CONTAINING THEREOF AND ITS USE |
| KR101071748B1 (ko) * | 2003-12-23 | 2011-10-11 | 아스텔라스세이야쿠 가부시키가이샤 | 아미노알콜 유도체 |
| US7915309B2 (en) * | 2007-06-20 | 2011-03-29 | Protia, Llc | Deuterium-enriched oseltamivir |
| TWI478712B (zh) | 2008-09-30 | 2015-04-01 | Astellas Pharma Inc | 釋控性醫藥組成物 |
| WO2010118291A2 (en) | 2009-04-10 | 2010-10-14 | Auspex Pharmaceuticals, Inc. | Biphenyl-3-carboxylic acid modulators of beta-3-adrenoreceptor |
| US9522129B2 (en) | 2010-08-03 | 2016-12-20 | Velicept Therapeutics, Inc. | Pharmaceutical Combination |
| NZ607485A (en) | 2010-08-03 | 2015-04-24 | Altherx Inc | Combinations of beta - 3 adrenergic receptor agonists and muscarinic receptor antagonists for treating overactive bladder |
| US9907767B2 (en) | 2010-08-03 | 2018-03-06 | Velicept Therapeutics, Inc. | Pharmaceutical compositions and the treatment of overactive bladder |
| HK1204966A1 (en) | 2012-02-09 | 2015-12-11 | Velicept Therapeutics, Inc. | Combination of muscarinic receptor antagonists and beta- 3 adrenoceptor agonists for treating overactive bladder |
| WO2014108449A1 (en) | 2013-01-08 | 2014-07-17 | Atrogi Ab | A screening method, a kit, a method of treatment and a compound for use in a method of treatment |
| US9956194B2 (en) | 2014-12-03 | 2018-05-01 | Velicept Therapeutics, Inc. | Compositions and methods of using modified release solabegron for lower urinary tract symptoms |
| PL3365321T3 (pl) | 2015-10-23 | 2024-03-25 | B3Ar Therapeutics, Inc. | Jon obojnaczy solabegronu i jego zastosowania |
| US12102638B2 (en) | 2017-06-06 | 2024-10-01 | Urovant Sciences Gmbh | Use of vibegron to treat overactive bladder |
| GB201714736D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714734D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714745D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714740D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| TW202038963A (zh) | 2018-12-05 | 2020-11-01 | 瑞士商優洛凡特科學公司 | 維貝隆(vibegron)於治療患有良性前列腺增生之男性中膀胱過動症症狀之用途 |
| GB201903832D0 (en) | 2019-03-20 | 2019-05-01 | Atrogi Ab | New compounds and methods |
| GB202205895D0 (en) | 2022-04-22 | 2022-06-08 | Atrogi Ab | New medical uses |
| US12097189B1 (en) | 2024-02-09 | 2024-09-24 | Astellas Pharma Inc. | Pharmaceutical composition for modified release |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0006735B1 (en) | 1978-06-28 | 1983-06-15 | Beecham Group Plc | Secondary amines, their preparation, pharmaceutical compositions containing them and their use |
| GB8519154D0 (en) | 1985-07-30 | 1985-09-04 | Ici Plc | Aromatic ethers |
| DE3934436A1 (de) | 1989-06-01 | 1991-04-18 | Thomae Gmbh Dr K | 2-hydroxy-n-propylamine, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| US5061727A (en) * | 1990-05-04 | 1991-10-29 | American Cyanamid Company | Substituted 5-(2-((2-aryl-2-hydroxyethyl)amino)propyl)-1,3-benzodioxoles |
| NO179246C (no) * | 1991-11-20 | 1996-09-04 | Sankyo Co | Aromatiske amino-alkoholderivater og mellomprodukter til fremstilling derav |
| AU2737295A (en) * | 1994-06-09 | 1996-01-04 | Glaxo Group Limited | Phenethanolamine derivatives and their use as atypical beta-adrenoceptor agonists |
-
1998
- 1998-06-13 GB GBGB9812709.5A patent/GB9812709D0/en not_active Ceased
-
1999
- 1999-06-09 AP APAP/P/2001/002028A patent/AP1687A/en active
- 1999-06-09 DK DK99927923T patent/DK1087943T3/da active
- 1999-06-09 AT AT99927923T patent/ATE302189T1/de active
- 1999-06-09 ID IDW20010101A patent/ID27841A/id unknown
- 1999-06-09 CZ CZ20004648A patent/CZ299172B6/cs not_active IP Right Cessation
- 1999-06-09 BR BRPI9911182-9A patent/BR9911182B1/pt not_active IP Right Cessation
- 1999-06-09 HU HU0102668A patent/HUP0102668A3/hu unknown
- 1999-06-09 AU AU45103/99A patent/AU753004B2/en not_active Expired
- 1999-06-09 DE DE69926752T patent/DE69926752T2/de not_active Expired - Lifetime
- 1999-06-09 CA CA002334713A patent/CA2334713C/en not_active Expired - Lifetime
- 1999-06-09 SK SK1908-2000A patent/SK286256B6/sk not_active IP Right Cessation
- 1999-06-09 EA EA200001172A patent/EA003641B1/ru not_active IP Right Cessation
- 1999-06-09 IL IL14021999A patent/IL140219A0/xx active IP Right Grant
- 1999-06-09 US US09/719,595 patent/US6251925B1/en not_active Expired - Lifetime
- 1999-06-09 RS YUP-792/00A patent/RS49921B/sr unknown
- 1999-06-09 PL PL344865A patent/PL196943B1/pl unknown
- 1999-06-09 SI SI9930827T patent/SI1087943T1/sl unknown
- 1999-06-09 HR HR20000854A patent/HRP20000854B1/xx not_active IP Right Cessation
- 1999-06-09 CO CO99036228A patent/CO5060482A1/es unknown
- 1999-06-09 KR KR10-2000-7014098A patent/KR100415877B1/ko not_active Expired - Lifetime
- 1999-06-09 EE EEP200000744A patent/EE04435B1/xx not_active IP Right Cessation
- 1999-06-09 TR TR2001/00299T patent/TR200100299T2/xx unknown
- 1999-06-09 AR ARP990102733A patent/AR029301A1/es active IP Right Grant
- 1999-06-09 WO PCT/EP1999/003958 patent/WO1999065877A1/en active IP Right Grant
- 1999-06-09 ES ES99927923T patent/ES2245107T3/es not_active Expired - Lifetime
- 1999-06-09 JP JP2000554704A patent/JP3471754B2/ja not_active Expired - Lifetime
- 1999-06-09 NZ NZ508805A patent/NZ508805A/en not_active IP Right Cessation
- 1999-06-09 CN CNB99809630XA patent/CN1214008C/zh not_active Expired - Lifetime
- 1999-06-09 EP EP99927923A patent/EP1087943B1/en not_active Expired - Lifetime
- 1999-06-10 PE PE1999000517A patent/PE20000726A1/es not_active Application Discontinuation
- 1999-06-10 MY MYPI99002368A patent/MY119542A/en unknown
- 1999-06-10 EG EG70199A patent/EG23856A/xx active
- 1999-06-16 TW TW088110054A patent/TWI244471B/zh not_active IP Right Cessation
-
2000
- 2000-12-08 IS IS5760A patent/IS2277B/is unknown
- 2000-12-11 IL IL140219A patent/IL140219A/en not_active IP Right Cessation
- 2000-12-12 ZA ZA200007417A patent/ZA200007417B/en unknown
- 2000-12-12 NO NO20006319A patent/NO318782B1/no not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20160609 |