SK3342002A3 - Biphenyl derivatives used as nhe-3 inhibitors - Google Patents

Biphenyl derivatives used as nhe-3 inhibitors Download PDF

Info

Publication number: SK3342002A3
Authority: SK; Slovakia
Prior art keywords: biphenyl; formula; group; nhe; coor
Prior art date: 1999-09-22

Application number

SK334-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Dieter Dorsch

Peter Raddatz

Norbert Beier

Claudia Wilm

Original Assignee

Merck Patent Gmbh

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-09-22

Filing date

2000-09-04

Publication date

2002-07-02

2000-09-04 Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh

2002-07-02 Publication of SK3342002A3 publication Critical patent/SK3342002A3/sk

Links

239000003112 inhibitor Substances 0.000 title claims abstract description 18
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title claims description 9
150000001875 compounds Chemical class 0.000 claims abstract description 59
108091006649 SLC9A3 Proteins 0.000 claims abstract description 19
102000046061 Sodium-Hydrogen Exchanger 3 Human genes 0.000 claims abstract 3
150000003839 salts Chemical class 0.000 claims description 23
238000011282 treatment Methods 0.000 claims description 21
239000012453 solvate Substances 0.000 claims description 16
239000003814 drug Substances 0.000 claims description 14
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 11
230000000302 ischemic effect Effects 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
210000000056 organ Anatomy 0.000 claims description 7
239000004480 active ingredient Substances 0.000 claims description 6
230000004663 cell proliferation Effects 0.000 claims description 6
230000002093 peripheral effect Effects 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
208000007536 Thrombosis Diseases 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
125000001624 naphthyl group Chemical group 0.000 claims description 5
238000011321 prophylaxis Methods 0.000 claims description 5
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
229910052740 iodine Inorganic materials 0.000 claims description 4
230000035939 shock Effects 0.000 claims description 4
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 3
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
210000003169 central nervous system Anatomy 0.000 claims description 3
208000020832 chronic kidney disease Diseases 0.000 claims description 3
210000002216 heart Anatomy 0.000 claims description 3
210000001428 peripheral nervous system Anatomy 0.000 claims description 3
238000004321 preservation Methods 0.000 claims description 3
208000023504 respiratory system disease Diseases 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
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 description 2
208000030090 Acute Disease Diseases 0.000 claims description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
230000001154 acute effect Effects 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000002795 guanidino group Chemical group C(N)(=N)N* 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
229910052760 oxygen Inorganic materials 0.000 claims description 2
239000001301 oxygen 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
230000001771 impaired effect Effects 0.000 claims 1
208000017169 kidney disease Diseases 0.000 claims 1
CGTAFLMPFCRKJU-UHFFFAOYSA-N methyl 2-[3-[(4-carbamimidoylphenoxy)methyl]-5-(3-carbamimidoylphenyl)phenoxy]acetate Chemical compound C=1C(C=2C=C(C=CC=2)C(N)=N)=CC(OCC(=O)OC)=CC=1COC1=CC=C(C(N)=N)C=C1 CGTAFLMPFCRKJU-UHFFFAOYSA-N 0.000 claims 1
238000002054 transplantation Methods 0.000 claims 1
239000011734 sodium Substances 0.000 abstract description 22
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 6
-1 3, 3-dimethylbutyl Chemical group 0.000 description 91
239000000243 solution Substances 0.000 description 33
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
210000004027 cell Anatomy 0.000 description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
210000003743 erythrocyte Anatomy 0.000 description 19
239000001257 hydrogen Substances 0.000 description 18
229910052739 hydrogen Inorganic materials 0.000 description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
102100030375 Sodium/hydrogen exchanger 3 Human genes 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
102000001708 Protein Isoforms Human genes 0.000 description 13
108010029485 Protein Isoforms Proteins 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
239000000872 buffer Substances 0.000 description 11
239000000203 mixture Substances 0.000 description 11
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
239000002253 acid Substances 0.000 description 10
238000011534 incubation Methods 0.000 description 10
125000006239 protecting group Chemical group 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000010521 absorption reaction Methods 0.000 description 9
125000002252 acyl group Chemical group 0.000 description 9
238000000034 method Methods 0.000 description 9
239000002904 solvent Substances 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
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 8
229910000564 Raney nickel Inorganic materials 0.000 description 8
102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 description 8
102100022897 Sodium/hydrogen exchanger 10 Human genes 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 description 8
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 7
239000007868 Raney catalyst Substances 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000012528 membrane Substances 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
238000012360 testing method Methods 0.000 description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
238000005119 centrifugation Methods 0.000 description 5
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 5
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 5
150000002431 hydrogen Chemical class 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
239000007787 solid Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
238000010626 work up procedure Methods 0.000 description 5
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
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
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KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
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241000283973 Oryctolagus cuniculus Species 0.000 description 4
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
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
208000006011 Stroke Diseases 0.000 description 4
244000166550 Strophanthus gratus Species 0.000 description 4
229930006000 Sucrose Natural products 0.000 description 4
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
239000007983 Tris buffer Substances 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
239000002585 base Substances 0.000 description 4
150000001735 carboxylic acids Chemical class 0.000 description 4
239000003480 eluent Substances 0.000 description 4
238000007327 hydrogenolysis reaction Methods 0.000 description 4
210000003734 kidney Anatomy 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
229960003343 ouabain Drugs 0.000 description 4
230000020477 pH reduction Effects 0.000 description 4
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
230000009467 reduction Effects 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
239000005720 sucrose Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
235000019743 Choline chloride Nutrition 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
239000007993 MOPS buffer Substances 0.000 description 3
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
102100030382 Sodium/hydrogen exchanger 2 Human genes 0.000 description 3
101710152953 Sodium/hydrogen exchanger 2 Proteins 0.000 description 3
BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000013543 active substance Substances 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
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229910000024 caesium carbonate Inorganic materials 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 3
229960003178 choline chloride Drugs 0.000 description 3
125000004093 cyano group Chemical group *C#N 0.000 description 3
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230000000694 effects Effects 0.000 description 3
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229960004198 guanidine Drugs 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
230000003834 intracellular effect Effects 0.000 description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
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239000000126 substance Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 2
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 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
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ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 2
ZCLSEGXBWAWWPV-UHFFFAOYSA-N 3-[3-(bromomethyl)phenyl]benzonitrile Chemical compound BrCC1=CC=CC(C=2C=C(C=CC=2)C#N)=C1 ZCLSEGXBWAWWPV-UHFFFAOYSA-N 0.000 description 2
STXAVEHFKAXGOX-UHFFFAOYSA-N 3-bromobenzonitrile Chemical compound BrC1=CC=CC(C#N)=C1 STXAVEHFKAXGOX-UHFFFAOYSA-N 0.000 description 2
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 2
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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
230000003204 osmotic effect Effects 0.000 description 1
150000004866 oxadiazoles Chemical class 0.000 description 1
BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
229910052763 palladium Inorganic materials 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
239000012188 paraffin wax Substances 0.000 description 1
230000001991 pathophysiological 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
229940066842 petrolatum Drugs 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
150000003016 phosphoric acids Chemical class 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
229920000642 polymer 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
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
239000000047 product Substances 0.000 description 1
230000002062 proliferating effect Effects 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
210000002307 prostate Anatomy 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000002901 radioactive waste Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000010079 rubber tapping Methods 0.000 description 1
238000007127 saponification reaction Methods 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
238000010898 silica gel chromatography Methods 0.000 description 1
208000019116 sleep disease Diseases 0.000 description 1
208000020685 sleep-wake disease Diseases 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229910001415 sodium ion Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 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
235000019698 starch Nutrition 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000003860 storage Methods 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 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
239000000829 suppository Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical group CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000000451 tissue damage Effects 0.000 description 1
231100000827 tissue damage Toxicity 0.000 description 1
125000005425 toluyl group Chemical group 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 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
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical class OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
208000027185 varicose disease Diseases 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
229930003231 vitamin Natural products 0.000 description 1
235000013343 vitamin Nutrition 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)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Hematology (AREA)
Diabetes (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Neurology (AREA)
Urology & Nephrology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Vascular Medicine (AREA)
Obesity (AREA)
Pulmonology (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)

SK334-2002A 1999-09-22 2000-09-04 Biphenyl derivatives used as nhe-3 inhibitors SK3342002A3 (en)

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
SK3342002A3 true SK3342002A3 (en)	2002-07-02

Family

ID=7922831

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK334-2002A SK3342002A3 (en)	1999-09-22	2000-09-04	Biphenyl derivatives used as nhe-3 inhibitors

Country Status (16)

Country	Link
EP (1)	EP1214291A1 (no)
JP (1)	JP2004500338A (no)
KR (1)	KR20020033818A (no)
CN (1)	CN1555356A (no)
AU (1)	AU7649700A (no)
BR (1)	BR0014199A (no)
CA (1)	CA2387529A1 (no)
CZ (1)	CZ2002815A3 (no)
DE (1)	DE19945302A1 (no)
HU (1)	HUP0202891A3 (no)
MX (1)	MXPA02003087A (no)
NO (1)	NO20021407L (no)
PL (1)	PL355097A1 (no)
SK (1)	SK3342002A3 (no)
WO (1)	WO2001021582A1 (no)
ZA (1)	ZA200203095B (no)

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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
GB0225548D0 (en)	2002-11-01	2002-12-11	Glaxo Group Ltd	Compounds
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
ATE479679T1 (de)	2007-06-28	2010-09-15	Sanofi Aventis Us Llc	Verfahren zur herstellung von n-(2-chlor-4-methyl-3-thienyl)-1h-benzimidazol- 2-amin hydrochlorid und zwischenprodukte dafür
EP2342178B1 (en) *	2008-09-02	2016-09-28	Sanofi	Substituted aminoindanes and analogs thereof, and the pharmaceutical use thereof
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
CN103819403B (zh)	2008-12-31	2017-01-04	阿德利克斯公司	用于治疗与体液潴留或盐超负荷有关的病症和胃肠道病症的化合物和方法
KR101879011B1 (ko)	2011-03-15	2018-07-16	아스테라스 세이야쿠 가부시키가이샤	구아니딘 화합물
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
RU2015107019A (ru)	2012-08-21	2016-10-10	Эрделикс Инк.	Соединения и способы для ингибирования nhe-опосредованного антипорта в лечении расстройств, ассоциированных с задержкой жидкости или солевой перегрузкой и заболеваний желудочно-кишечного тракта
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
CN105392483B (zh)	2013-04-12	2019-03-15	阿德利克斯公司	用于抑制磷酸盐转运的nhe3结合化合物和方法
WO2016013657A1 (ja)	2014-07-25	2016-01-28	大正製薬株式会社	ヘテロアリールで置換されたフェニルテトラヒドロイソキノリン化合物
EA201991676A1 (ru)	2017-01-09	2020-01-30	Арделикс, Инк.	Ингибиторы nhe-опосредованного антипорта
KR20240090875A (ko)	2017-01-09	2024-06-21	알데릭스, 인코포레이티드	위장관 장애를 치료하는 데 유용한 화합물
CN111386279A (zh)	2017-08-04	2020-07-07	阿德利克斯股份有限公司	用于治疗高钾血症的甘草次酸衍生物
JP7735185B2 (ja)	2019-02-07	2025-09-08	アルデリックス，インコーポレイテッド	高カリウム血症の治療で使用するためのグリチルレチン酸誘導体
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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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 CN CNA008131600A patent/CN1555356A/zh active Pending
- 2000-09-04 CA CA002387529A patent/CA2387529A1/en not_active Abandoned
- 2000-09-04 AU AU76497/00A patent/AU7649700A/en not_active Abandoned
- 2000-09-04 HU HU0202891A patent/HUP0202891A3/hu unknown
- 2000-09-04 PL PL00355097A patent/PL355097A1/xx unknown
- 2000-09-04 KR KR1020027003735A patent/KR20020033818A/ko not_active Withdrawn
- 2000-09-04 JP JP2001524962A patent/JP2004500338A/ja active Pending
- 2000-09-04 MX MXPA02003087A patent/MXPA02003087A/es unknown
- 2000-09-04 BR BR0014199-2A patent/BR0014199A/pt not_active IP Right Cessation
- 2000-09-04 EP EP00965915A patent/EP1214291A1/de not_active Withdrawn
- 2000-09-04 WO PCT/EP2000/008616 patent/WO2001021582A1/de not_active Ceased
- 2000-09-04 SK SK334-2002A patent/SK3342002A3/sk not_active Application Discontinuation
- 2000-09-04 CZ CZ2002815A patent/CZ2002815A3/cs unknown
2002
- 2002-03-21 NO NO20021407A patent/NO20021407L/no unknown
- 2002-04-18 ZA ZA200203095A patent/ZA200203095B/xx unknown

Also Published As

Publication number	Publication date
NO20021407D0 (no)	2002-03-21
PL355097A1 (en)	2004-03-22
AU7649700A (en)	2001-04-24
CA2387529A1 (en)	2001-03-29
BR0014199A (pt)	2002-05-21
NO20021407L (no)	2002-03-21
JP2004500338A (ja)	2004-01-08
EP1214291A1 (de)	2002-06-19
ZA200203095B (en)	2003-09-23
HUP0202891A3 (en)	2003-11-28
KR20020033818A (ko)	2002-05-07
WO2001021582A1 (de)	2001-03-29
HUP0202891A2 (hu)	2003-02-28
CN1555356A (zh)	2004-12-15
CZ2002815A3 (cs)	2002-08-14
DE19945302A1 (de)	2001-03-29
MXPA02003087A (es)	2003-08-20

Legal Events

Date	Code	Title	Description
2010-08-09	FC9A	Refused patent application

Publication	Publication Date	Title
CZ2002815A3 (cs)	2002-08-14	Deriváty bifenylu jakoľto NHE-3 inhibitory
ES2710662T3 (es)	2019-04-26	Compuestos de acilguanidina con actividad antiviral
CA2471524A1 (en)	2003-07-10	4-arylquinazolines and use thereof as nhe-3 inhibitors
PT889875E (pt)	2001-10-30	Derivados de acidos ciclopropilalcanoicos
HUT60462A (en)	1992-09-28	Process for producing biphenyl derivatives and pharmaceutical compositions comprising same
SK13472002A3 (sk)	2003-02-04	Derivát 2-guanidíno-4-arylchinazolínu ako NHE-3 inhibítor, jeho použitie a farmaceutický prostriedok, ktorý ho obsahuje
GB2083818A (en)	1982-03-31	Amidine compounds
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