JP2004500338A - Ｎｈｅ−３阻害剤として用いられるビフェニル誘導体 - Google Patents
Ｎｈｅ−３阻害剤として用いられるビフェニル誘導体 Download PDFInfo
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- JP2004500338A JP2004500338A JP2001524962A JP2001524962A JP2004500338A JP 2004500338 A JP2004500338 A JP 2004500338A JP 2001524962 A JP2001524962 A JP 2001524962A JP 2001524962 A JP2001524962 A JP 2001524962A JP 2004500338 A JP2004500338 A JP 2004500338A
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- biphenyl
- nhe
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- acid
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- 108091006649 SLC9A3 Proteins 0.000 title claims abstract description 23
- 239000003112 inhibitor Substances 0.000 title claims abstract description 21
- 102000046061 Sodium-Hydrogen Exchanger 3 Human genes 0.000 title claims abstract 5
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- -1 methyl [3'-amidino-5- (4-amidinophenoxymethyl) -biphenyl-3-yloxy] acetate Chemical class 0.000 claims description 97
- 150000003839 salts Chemical class 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 15
- 239000012453 solvate Substances 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 230000000302 ischemic effect Effects 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 210000000056 organ Anatomy 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 238000001356 surgical procedure Methods 0.000 claims description 5
- 208000007536 Thrombosis Diseases 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 208000017169 kidney disease Diseases 0.000 claims description 4
- 230000002093 peripheral effect Effects 0.000 claims description 4
- 230000000241 respiratory effect Effects 0.000 claims description 4
- 238000003860 storage Methods 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- QAIJMAFUGWSUFR-UHFFFAOYSA-N 3-[(3-carbamimidoylphenoxy)methyl]-5-(3-carbamimidoylphenyl)benzoic acid Chemical compound NC(=N)C1=CC=CC(OCC=2C=C(C=C(C=2)C(O)=O)C=2C=C(C=CC=2)C(N)=N)=C1 QAIJMAFUGWSUFR-UHFFFAOYSA-N 0.000 claims description 3
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 230000035939 shock Effects 0.000 claims description 3
- OMYRYWJJQSDEBR-UHFFFAOYSA-N 2-[3-[(4-carbamimidoylphenoxy)methyl]-5-(3-carbamimidoylphenyl)phenoxy]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1OCC1=CC(OCC(O)=O)=CC(C=2C=C(C=CC=2)C(N)=N)=C1 OMYRYWJJQSDEBR-UHFFFAOYSA-N 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 208000023569 ischemic bowel disease Diseases 0.000 claims description 2
- UPBDRALYKRMMSV-UHFFFAOYSA-N n-(diaminomethylidene)-3-[3-[[3-(diaminomethylidenecarbamoyl)phenoxy]methyl]phenyl]benzamide Chemical compound NC(=N)NC(=O)C1=CC=CC(OCC=2C=C(C=CC=2)C=2C=C(C=CC=2)C(=O)NC(N)=N)=C1 UPBDRALYKRMMSV-UHFFFAOYSA-N 0.000 claims description 2
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- XVWGCWQAXSLVAX-UHFFFAOYSA-N 3-[3-[(3-carbamimidoylphenoxy)methyl]phenyl]benzenecarboximidamide Chemical compound NC(=N)C1=CC=CC(OCC=2C=C(C=CC=2)C=2C=C(C=CC=2)C(N)=N)=C1 XVWGCWQAXSLVAX-UHFFFAOYSA-N 0.000 claims 1
- BPNWOLGYJJGREY-UHFFFAOYSA-N 3-[[3-(3-carbamimidoylphenyl)phenoxy]methyl]benzenecarboximidamide Chemical compound NC(=N)C1=CC=CC(COC=2C=C(C=CC=2)C=2C=C(C=CC=2)C(N)=N)=C1 BPNWOLGYJJGREY-UHFFFAOYSA-N 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- 210000002216 heart Anatomy 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 239000011734 sodium Substances 0.000 abstract description 12
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract description 8
- 229910052708 sodium Inorganic materials 0.000 abstract description 7
- 238000006243 chemical reaction Methods 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 25
- 238000010265 fast atom bombardment Methods 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 210000003743 erythrocyte Anatomy 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 102100030375 Sodium/hydrogen exchanger 3 Human genes 0.000 description 18
- 102000001708 Protein Isoforms Human genes 0.000 description 16
- 108010029485 Protein Isoforms Proteins 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
- 238000011534 incubation Methods 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 230000009102 absorption Effects 0.000 description 12
- 238000010521 absorption reaction Methods 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 239000000872 buffer Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 102100022897 Sodium/hydrogen exchanger 10 Human genes 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
- 102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000007868 Raney catalyst Substances 0.000 description 6
- 229910000564 Raney nickel Inorganic materials 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- QDERNBXNXJCIQK-UHFFFAOYSA-N ethylisopropylamiloride Chemical compound CCN(C(C)C)C1=NC(N)=C(C(=O)N=C(N)N)N=C1Cl QDERNBXNXJCIQK-UHFFFAOYSA-N 0.000 description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- TYBARJRCFHUHSN-DMJRSANLSA-N 3-[(1r,3s,5s,8r,9s,10r,11r,13r,14s,17r)-1,5,11,14-tetrahydroxy-10-(hydroxymethyl)-13-methyl-3-[(2r,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2h-furan-5-one;octahydrate Chemical compound O.O.O.O.O.O.O.O.O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 TYBARJRCFHUHSN-DMJRSANLSA-N 0.000 description 4
- LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 description 4
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- LPMXVESGRSUGHW-GHYGWZAOSA-N Ouabain Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1)[C@H]1C[C@@H](O)[C@@]2(CO)[C@@](O)(C1)CC[C@H]1[C@]3(O)[C@@](C)([C@H](C4=CC(=O)OC4)CC3)C[C@@H](O)[C@H]21 LPMXVESGRSUGHW-GHYGWZAOSA-N 0.000 description 4
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- 125000003277 amino group Chemical group 0.000 description 4
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- 230000012105 intracellular pH reduction Effects 0.000 description 4
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
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- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
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- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
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- XDBHWPLGGBLUHH-UHFFFAOYSA-N (3-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C#N)=C1 XDBHWPLGGBLUHH-UHFFFAOYSA-N 0.000 description 2
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
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- VEOJXCSYGJEFEX-UHFFFAOYSA-N methyl 3-[3-[(3-methoxycarbonylphenoxy)methyl]phenyl]benzoate Chemical compound COC(=O)C1=CC=CC(OCC=2C=C(C=CC=2)C=2C=C(C=CC=2)C(=O)OC)=C1 VEOJXCSYGJEFEX-UHFFFAOYSA-N 0.000 description 1
- OAOZBFUAVJUPED-UHFFFAOYSA-N methyl 3-bromo-5-methylbenzoate Chemical compound COC(=O)C1=CC(C)=CC(Br)=C1 OAOZBFUAVJUPED-UHFFFAOYSA-N 0.000 description 1
- KMFJVYMFCAIRAN-UHFFFAOYSA-N methyl 3-bromobenzoate Chemical compound COC(=O)C1=CC=CC(Br)=C1 KMFJVYMFCAIRAN-UHFFFAOYSA-N 0.000 description 1
- 229940120152 methyl 3-hydroxybenzoate Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- NMLAPMPFWBKYBX-UHFFFAOYSA-N n'-hydroxy-3-[3-[[3-(n'-hydroxycarbamimidoyl)phenoxy]methyl]phenyl]benzenecarboximidamide Chemical compound ONC(=N)C1=CC=CC(OCC=2C=C(C=CC=2)C=2C=C(C=CC=2)C(=N)NO)=C1 NMLAPMPFWBKYBX-UHFFFAOYSA-N 0.000 description 1
- IEVJZFMFGKOJSR-UHFFFAOYSA-N n-(diaminomethylidene)-3-[[3-[3-(diaminomethylidenecarbamoyl)phenyl]phenoxy]methyl]benzamide Chemical compound NC(N)=NC(=O)C1=CC=CC(COC=2C=C(C=CC=2)C=2C=C(C=CC=2)C(=O)N=C(N)N)=C1 IEVJZFMFGKOJSR-UHFFFAOYSA-N 0.000 description 1
- JFESASXRVFKAFH-UHFFFAOYSA-N n-(diaminomethylidene)-3-[[3-[4-(diaminomethylidenecarbamoyl)phenyl]phenoxy]methyl]benzamide Chemical compound C1=CC(C(=O)N=C(N)N)=CC=C1C1=CC=CC(OCC=2C=C(C=CC=2)C(=O)N=C(N)N)=C1 JFESASXRVFKAFH-UHFFFAOYSA-N 0.000 description 1
- BQGKHBVEZBTERM-UHFFFAOYSA-N n-(diaminomethylidene)-4-[4-[[4-(diaminomethylidenecarbamoyl)phenoxy]methyl]phenyl]benzamide Chemical compound C1=CC(C(=O)N=C(N)N)=CC=C1OCC1=CC=C(C=2C=CC(=CC=2)C(=O)N=C(N)N)C=C1 BQGKHBVEZBTERM-UHFFFAOYSA-N 0.000 description 1
- JYYFUYLSAIKZDR-UHFFFAOYSA-N n-(diaminomethylidene)-4-[[3-[4-(diaminomethylidenecarbamoyl)phenyl]phenoxy]methyl]benzamide Chemical compound C1=CC(C(=O)N=C(N)N)=CC=C1COC1=CC=CC(C=2C=CC(=CC=2)C(=O)N=C(N)N)=C1 JYYFUYLSAIKZDR-UHFFFAOYSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 125000001400 nonyl 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])C([H])([H])[H] 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
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000036278 prepulse Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-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
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 210000000512 proximal kidney tubule Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002901 radioactive waste Substances 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/22—Y being a hydrogen or a carbon atom, e.g. benzoylguanidines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- 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
- A61P9/10—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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19945302A DE19945302A1 (de) | 1999-09-22 | 1999-09-22 | Biphenylderivate als NHE-3-Inhibitoren |
| PCT/EP2000/008616 WO2001021582A1 (de) | 1999-09-22 | 2000-09-04 | Biphenylderivate als nhe-3-inhibitoren |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2004500338A true JP2004500338A (ja) | 2004-01-08 |
Family
ID=7922831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001524962A Pending JP2004500338A (ja) | 1999-09-22 | 2000-09-04 | Ｎｈｅ−３阻害剤として用いられるビフェニル誘導体 |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP1214291A1 (zh) |
| JP (1) | JP2004500338A (zh) |
| KR (1) | KR20020033818A (zh) |
| CN (1) | CN1555356A (zh) |
| AU (1) | AU7649700A (zh) |
| BR (1) | BR0014199A (zh) |
| CA (1) | CA2387529A1 (zh) |
| CZ (1) | CZ2002815A3 (zh) |
| DE (1) | DE19945302A1 (zh) |
| HU (1) | HUP0202891A3 (zh) |
| MX (1) | MXPA02003087A (zh) |
| NO (1) | NO20021407D0 (zh) |
| PL (1) | PL355097A1 (zh) |
| SK (1) | SK3342002A3 (zh) |
| WO (1) | WO2001021582A1 (zh) |
| ZA (1) | ZA200203095B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8716470B2 (en) | 2011-03-15 | 2014-05-06 | Astellas Pharma Inc. | Guanidine compound |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10163239A1 (de) * | 2001-12-21 | 2003-07-10 | Aventis Pharma Gmbh | Substituierte Imidazolidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie enthaltendes Medikament |
| US7049333B2 (en) | 2002-06-04 | 2006-05-23 | Sanofi-Aventis Deutschland Gmbh | Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis |
| DE10304374A1 (de) | 2003-02-04 | 2004-08-05 | Aventis Pharma Deutschland Gmbh | Neue substituierte 2-Aminoimidazole, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| US20050054705A1 (en) | 2003-02-04 | 2005-03-10 | Aventis Pharma Deutschland Gmbh | N-substituted (benzoimidazol-2-yl) phenylamines, process for their preparation, their use as medicament or diagnostic aid, and medicament comprising them |
| DE10341240A1 (de) | 2003-09-08 | 2005-04-07 | Aventis Pharma Deutschland Gmbh | Substituierte Thienoimidazole, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| US7534894B2 (en) | 2003-09-25 | 2009-05-19 | Wyeth | Biphenyloxy-acids |
| DE102005001411A1 (de) | 2005-01-12 | 2006-07-27 | Sanofi-Aventis Deutschland Gmbh | Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament |
| EP2170872B1 (en) | 2007-06-28 | 2010-09-01 | Sanofi-Aventis U.S. LLC | Process for the preparation of the n-(2-chloro-4-methyl-3-thienyl)-1h- benzimidazol-2-amine hydrochloride and intermediates thereof |
| JP5745406B2 (ja) | 2008-09-02 | 2015-07-08 | サノフイ | 置換アミノインダン及びそのアナログ、及びその医薬使用 |
| WO2018129556A1 (en) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| ES2657938T3 (es) | 2008-12-31 | 2018-03-07 | Ardelyx, Inc. | Compuestos y métodos para inhibir el antipuerto mediado por NHE en el tratamiento de trastornos asociados a la retención de líquidos o a la sobrecarga de sales y trastornos del tracto gastrointestinal |
| CN103012200B (zh) * | 2011-09-20 | 2014-12-17 | 北京大学 | 具有β-分泌酶抑制功能的化合物及其制备方法与应用 |
| US10376481B2 (en) | 2012-08-21 | 2019-08-13 | Ardelyx, Inc. | Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| CN104902930A (zh) | 2012-08-21 | 2015-09-09 | 阿德利克斯公司 | 在治疗与液体潴留或盐分过载相关的疾病和胃肠道疾病中用于抑制nhe-介导的反向转运的化合物和方法 |
| ES2735992T3 (es) | 2013-04-12 | 2019-12-23 | Ardelyx Inc | Compuestos de unión a NHE3 y procedimientos para inhibir el transporte de fosfatos |
| LT3173408T (lt) | 2014-07-25 | 2018-12-27 | Taisho Pharmaceutical Co., Ltd. | Fenilo tetrahidroizochinolino junginys, turintis heteroarilo pakaitų |
| EP3565808A1 (en) | 2017-01-09 | 2019-11-13 | Ardelyx, Inc. | Compounds useful for treating gastrointestinal tract disorders |
| EA201991676A1 (ru) | 2017-01-09 | 2020-01-30 | Арделикс, Инк. | Ингибиторы nhe-опосредованного антипорта |
| BR112020002322A2 (pt) | 2017-08-04 | 2020-09-01 | Ardelyx, Inc. | derivados de ácido glicirretinínico para o tratamento de hipercalemia |
| AU2020218255A1 (en) | 2019-02-07 | 2021-09-09 | Ardelyx, Inc. | Glycyrrhetinic acid derivatives for use in treating hyperkalemia |
| JP2022533251A (ja) | 2019-05-21 | 2022-07-21 | アルデリックス， インコーポレイテッド | 患者において血清リン酸塩を低下させるための組み合わせ |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19548812A1 (de) * | 1995-12-27 | 1997-07-03 | Hoechst Ag | Verwendung von Inhibitoren des zellulären Na·+·/H·+·-Exchangers (NHE) zur Herstellung eines Medikaments zur Atemstimulation |
| DE19622222A1 (de) * | 1996-06-03 | 1997-12-04 | Hoechst Ag | Verwendung von Inhibitoren des zellulären Na·+·/H·+·-Exchangers (NHE) zur Herstellung eines Medikament zur Normalisierung der Serumlipide |
| DE19737224A1 (de) * | 1997-08-27 | 1999-03-18 | Hoechst Marion Roussel De Gmbh | Pharmazeutisches Kombinationspräparat aus einem Inhibitor des Natrium-Wasserstoff-Austauschers und einem Arzneimittel zur Behandlung von Herz-Kreislauferkrankungen |
| DE19819548A1 (de) * | 1998-04-30 | 1999-11-04 | Merck Patent Gmbh | Biphenylderivate |
-
1999
- 1999-09-22 DE DE19945302A patent/DE19945302A1/de not_active Withdrawn
-
2000
- 2000-09-04 WO PCT/EP2000/008616 patent/WO2001021582A1/de not_active Application Discontinuation
- 2000-09-04 CN CNA008131600A patent/CN1555356A/zh active Pending
- 2000-09-04 MX MXPA02003087A patent/MXPA02003087A/es unknown
- 2000-09-04 EP EP00965915A patent/EP1214291A1/de not_active Withdrawn
- 2000-09-04 CA CA002387529A patent/CA2387529A1/en not_active Abandoned
- 2000-09-04 JP JP2001524962A patent/JP2004500338A/ja active Pending
- 2000-09-04 SK SK334-2002A patent/SK3342002A3/sk not_active Application Discontinuation
- 2000-09-04 KR KR1020027003735A patent/KR20020033818A/ko not_active Application Discontinuation
- 2000-09-04 PL PL00355097A patent/PL355097A1/xx unknown
- 2000-09-04 HU HU0202891A patent/HUP0202891A3/hu unknown
- 2000-09-04 BR BR0014199-2A patent/BR0014199A/pt not_active IP Right Cessation
- 2000-09-04 CZ CZ2002815A patent/CZ2002815A3/cs unknown
- 2000-09-04 AU AU76497/00A patent/AU7649700A/en not_active Abandoned
-
2002
- 2002-03-21 NO NO20021407A patent/NO20021407D0/no unknown
- 2002-04-18 ZA ZA200203095A patent/ZA200203095B/xx unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8716470B2 (en) | 2011-03-15 | 2014-05-06 | Astellas Pharma Inc. | Guanidine compound |
| US9051283B2 (en) | 2011-03-15 | 2015-06-09 | Astellas Pharma Inc. | Guanidine compound |
| US9556160B2 (en) | 2011-03-15 | 2017-01-31 | Astellas Pharma Inc. | Guanidine compound |
Also Published As
| Publication number | Publication date |
|---|---|
| NO20021407L (no) | 2002-03-21 |
| MXPA02003087A (es) | 2003-08-20 |
| CN1555356A (zh) | 2004-12-15 |
| EP1214291A1 (de) | 2002-06-19 |
| BR0014199A (pt) | 2002-05-21 |
| ZA200203095B (en) | 2003-09-23 |
| WO2001021582A1 (de) | 2001-03-29 |
| KR20020033818A (ko) | 2002-05-07 |
| HUP0202891A3 (en) | 2003-11-28 |
| CZ2002815A3 (cs) | 2002-08-14 |
| NO20021407D0 (no) | 2002-03-21 |
| DE19945302A1 (de) | 2001-03-29 |
| SK3342002A3 (en) | 2002-07-02 |
| PL355097A1 (en) | 2004-03-22 |
| HUP0202891A2 (hu) | 2003-02-28 |
| AU7649700A (en) | 2001-04-24 |
| CA2387529A1 (en) | 2001-03-29 |
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