NO310497B1 - Pyrimidin- eller triazin-karboksylsyrederivater, hvilke kan anvendes som legemidler - Google Patents

Pyrimidin- eller triazin-karboksylsyrederivater, hvilke kan anvendes som legemidler Download PDF

Info

Publication number: NO310497B1
Authority: NO; Norway
Prior art keywords: alkyl; phenyl; halogen; endothelin; compounds
Prior art date: 1994-03-31

Application number

NO19964121A

Other languages

English (en)

Norwegian (no)

Other versions

NO964121L (no

NO964121D0 (no

Inventor

Ernst Baumann

Uwe Josef Vogelbacher

Joachim Rheinheimer

Dagmar Klinge

Hartmut Riechers

Burkhard Kroeger

Siegfried Bialojan

Claus Bollschweiler

Wolfgang Wernet

Liliane Unger

Manfred Raschack

Original Assignee

Basf Ag

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.)

1994-03-31

Filing date

1996-09-27

Publication date

2001-07-16

1996-09-27 Application filed by Basf Ag filed Critical Basf Ag

1996-09-27 Publication of NO964121D0 publication Critical patent/NO964121D0/no

1996-11-26 Publication of NO964121L publication Critical patent/NO964121L/no

2001-07-16 Publication of NO310497B1 publication Critical patent/NO310497B1/no

Links

239000003814 drug Substances 0.000 title claims description 3
229940079593 drug Drugs 0.000 title description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title 1
UCAJPHQTEWYXEA-UHFFFAOYSA-N triazine-4-carboxylic acid Chemical class OC(=O)C1=CC=NN=N1 UCAJPHQTEWYXEA-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 33
-1 cyano, hydroxy Chemical group 0.000 claims description 13
229910052736 halogen Inorganic materials 0.000 claims description 13
150000002367 halogens Chemical class 0.000 claims description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
125000004450 alkenylene group Chemical group 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
229940124597 therapeutic agent Drugs 0.000 claims 1
102000010180 Endothelin receptor Human genes 0.000 abstract description 4
108050001739 Endothelin receptor Proteins 0.000 abstract description 4
238000000034 method Methods 0.000 abstract description 3
230000002401 inhibitory effect Effects 0.000 abstract 1
239000002904 solvent Substances 0.000 description 18
108050009340 Endothelin Proteins 0.000 description 17
102000002045 Endothelin Human genes 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 17
238000012360 testing method Methods 0.000 description 15
239000000203 mixture Substances 0.000 description 14
210000004027 cell Anatomy 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
238000004821 distillation Methods 0.000 description 10
150000002168 ethanoic acid esters Chemical class 0.000 description 10
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
102000005962 receptors Human genes 0.000 description 9
108020003175 receptors Proteins 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
238000003756 stirring Methods 0.000 description 8
238000001035 drying Methods 0.000 description 7
239000000843 powder Substances 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
239000000243 solution Substances 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
230000027455 binding Effects 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
101800004490 Endothelin-1 Proteins 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000000872 buffer Substances 0.000 description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
239000012528 membrane Substances 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
102100033902 Endothelin-1 Human genes 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
206010020772 Hypertension Diseases 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000013543 active substance Substances 0.000 description 3
239000003513 alkali Substances 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
230000037396 body weight Effects 0.000 description 3
231100000673 dose–response relationship Toxicity 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000007788 liquid Substances 0.000 description 3
MPUUYNKMYOCSAO-UHFFFAOYSA-N methyl 2-(4,6-dimethoxypyrimidin-2-yl)oxy-3-phenoxy-3-phenylbutanoate Chemical compound C=1C=CC=CC=1OC(C)(C=1C=CC=CC=1)C(C(=O)OC)OC1=NC(OC)=CC(OC)=N1 MPUUYNKMYOCSAO-UHFFFAOYSA-N 0.000 description 3
ODHISWLLJYLTSF-UHFFFAOYSA-N methyl 2-(4,6-dimethoxypyrimidin-2-yl)oxy-3-phenyl-3-phenylmethoxybutanoate Chemical compound C=1C=CC=CC=1COC(C)(C=1C=CC=CC=1)C(C(=O)OC)OC1=NC(OC)=CC(OC)=N1 ODHISWLLJYLTSF-UHFFFAOYSA-N 0.000 description 3
AGZSSAGYWIIPFE-UHFFFAOYSA-N methyl 3-methyl-3-phenyloxirane-2-carboxylate Chemical compound COC(=O)C1OC1(C)C1=CC=CC=C1 AGZSSAGYWIIPFE-UHFFFAOYSA-N 0.000 description 3
AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 description 2
PCVRHOZHSQQRMC-UHFFFAOYSA-N 4,6-dimethoxy-1h-pyrimidine-2-thione Chemical compound COC1=CC(OC)=NC(S)=N1 PCVRHOZHSQQRMC-UHFFFAOYSA-N 0.000 description 2
ITDVJJVNAASTRS-UHFFFAOYSA-N 4,6-dimethoxy-2-methylsulfonylpyrimidine Chemical compound COC1=CC(OC)=NC(S(C)(=O)=O)=N1 ITDVJJVNAASTRS-UHFFFAOYSA-N 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
229940118365 Endothelin receptor antagonist Drugs 0.000 description 2
102100040611 Endothelin receptor type B Human genes 0.000 description 2
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 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
102000001708 Protein Isoforms Human genes 0.000 description 2
108010029485 Protein Isoforms Proteins 0.000 description 2
241000700159 Rattus Species 0.000 description 2
208000001647 Renal Insufficiency Diseases 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
206010047139 Vasoconstriction Diseases 0.000 description 2
239000002253 acid Substances 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
238000010171 animal model Methods 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
235000019445 benzyl alcohol Nutrition 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000011575 calcium Substances 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
230000002490 cerebral effect Effects 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
230000008602 contraction Effects 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
239000002308 endothelin receptor antagonist Substances 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000011534 incubation Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
201000006370 kidney failure Diseases 0.000 description 2
231100000518 lethal Toxicity 0.000 description 2
230000001665 lethal effect Effects 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
239000012139 lysis buffer Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
XXRIHIOVKDEJPJ-UHFFFAOYSA-N methyl 2-hydroxy-3-phenoxy-3-phenylbutanoate Chemical compound C=1C=CC=CC=1C(C)(C(O)C(=O)OC)OC1=CC=CC=C1 XXRIHIOVKDEJPJ-UHFFFAOYSA-N 0.000 description 2
DYDIMXGJVTUIIK-UHFFFAOYSA-N methyl 2-hydroxy-3-phenyl-3-phenylmethoxybutanoate Chemical compound C=1C=CC=CC=1C(C)(C(O)C(=O)OC)OCC1=CC=CC=C1 DYDIMXGJVTUIIK-UHFFFAOYSA-N 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
239000003921 oil Substances 0.000 description 2
150000002924 oxiranes Chemical class 0.000 description 2
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BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
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239000000725 suspension Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
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WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
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HEHKOOYUSXOITQ-UHFFFAOYSA-N 2-(4,6-dimethoxypyrimidin-2-yl)oxy-3-phenyl-3-phenylmethoxybutanoic acid Chemical compound COC1=CC(OC)=NC(OC(C(O)=O)C(C)(OCC=2C=CC=CC=2)C=2C=CC=CC=2)=N1 HEHKOOYUSXOITQ-UHFFFAOYSA-N 0.000 description 1
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WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 1
CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
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WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
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Endocrinology (AREA)
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Toxicology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Medicinal Preparation (AREA)

NO19964121A 1994-03-31 1996-09-27 Pyrimidin- eller triazin-karboksylsyrederivater, hvilke kan anvendes som legemidler NO310497B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE4411225A DE4411225A1 (de)	1994-03-31	1994-03-31	Verwendung von Carbonsäurederivaten als Arzneimittel
PCT/EP1995/001099 WO1995026716A1 (de)	1994-03-31	1995-03-23	Pyrimidin- oder triazincarbonsäurederivate zur verwendung als arzneimittel

Publications (3)

Publication Number	Publication Date
NO964121D0 NO964121D0 (no)	1996-09-27
NO964121L NO964121L (no)	1996-11-26
NO310497B1 true NO310497B1 (no)	2001-07-16

Family

ID=6514334

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19964121A NO310497B1 (no)	1994-03-31	1996-09-27	Pyrimidin- eller triazin-karboksylsyrederivater, hvilke kan anvendes som legemidler

Country Status (28)

Country	Link
US (1)	US5840722A (fi)
EP (1)	EP0752854B1 (fi)
JP (2)	JP4001622B2 (fi)
KR (1)	KR100365629B1 (fi)
CN (1)	CN1070701C (fi)
AT (1)	ATE204471T1 (fi)
AU (1)	AU695193B2 (fi)
BR (1)	BR9507231A (fi)
CA (1)	CA2186784C (fi)
CZ (1)	CZ290684B6 (fi)
DE (2)	DE4411225A1 (fi)
DK (1)	DK0752854T3 (fi)
ES (1)	ES2162916T3 (fi)
FI (1)	FI118589B (fi)
GR (1)	GR3036606T3 (fi)
HR (1)	HRP950115B1 (fi)
HU (1)	HU228063B1 (fi)
IL (1)	IL113137A (fi)
NO (1)	NO310497B1 (fi)
NZ (1)	NZ283333A (fi)
PL (1)	PL179580B1 (fi)
PT (1)	PT752854E (fi)
RU (1)	RU2163808C2 (fi)
SI (1)	SI9520048A (fi)
TW (1)	TW382594B (fi)
UA (1)	UA44734C2 (fi)
WO (1)	WO1995026716A1 (fi)
ZA (1)	ZA952614B (fi)

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DE4411225A1 (de) *	1994-03-31	1995-10-05	Basf Ag	Verwendung von Carbonsäurederivaten als Arzneimittel
DE19533023B4 (de) *	1994-10-14	2007-05-16	Basf Ag	Neue Carbonsäurederivate, ihre Herstellung und Verwendung
DE19536891A1 (de) *	1995-10-04	1997-04-10	Basf Ag	Neue Aminosäurederivate, ihre Herstellung und Verwendung
DE19614533A1 (de)	1996-04-12	1997-10-16	Basf Ag	Neue alpha-Hydroxysäurederivate, ihre Herstellung und Verwendung
DE19614542A1 (de) *	1996-04-12	1997-10-16	Basf Ag	Neue Carbonsäurederivate, ihre Herstellung und Verwendung
DE19636046A1 (de) *	1996-09-05	1998-03-12	Basf Ag	Neue Carbonsäurederivate, ihre Herstellung und Verwendung als gemischte ET¶A¶/ET¶B¶-Rezeptorantagonisten
US6030975A (en) *	1997-03-14	2000-02-29	Basf Aktiengesellschaft	Carboxylic acid derivatives, their preparation and use in treating cancer
DE19726146A1 (de) *	1997-06-19	1998-12-24	Basf Ag	Neue ß-Amino und ß-Azidopcarbonsäurederivate, ihre Herstellung und Verwendung als Endothelinrezeptorantagonisten
IL134276A0 (en) *	1997-09-04	2001-04-30	Basf Ag	Novel carboxylic acid derivatives, their production and their use as mixed eta/etb endothelin-receptor antagonists
EP1027338A2 (de)	1997-10-31	2000-08-16	Basf Aktiengesellschaft	Neue carbonsäurederivate, die amidseitenketten tragen, ihre herstellung und verwendung als endothelin-rezeptorantagonisten
DE19806438A1 (de) *	1998-02-17	1999-08-19	Basf Ag	Neue Carbonsäurederivate mit 5-substituiertem Pyrimidinring, ihre Herstellung und Verwendung
DE19809144A1 (de) *	1998-03-04	1999-09-09	Basf Ag	Neue unsymmetrisch substituierte Carbonsäurederivate, ihre Herstellung und Verwendung als gemischte ET¶LAMBDA¶/ET¶B¶-Rezeptorantagonisten
DE19809635A1 (de)	1998-03-06	1999-09-09	Basf Ag	Verfahren zur Darstellung von Endothelinrezeptorantagonisten vom Sulfanyltyp
US7566452B1 (en)	1999-05-04	2009-07-28	New York University	Cancer treatment with endothelin receptor antagonists
WO2002064573A1 (de) *	2001-02-14	2002-08-22	Abbott Gmbh & Co. Kg	Neue carbonsäurederivate mit alkylsubstituierten triazinen, ihre herstellung und verwendung als endothelin-rezeptorantagonisten
US20040204422A1 (en)	2003-04-14	2004-10-14	Abbott Gmbh & Co. Kg.	N-[(Piperazinyl)hetaryl]arylsulfonamide compounds
WO2008097468A2 (en) *	2007-02-02	2008-08-14	Concert Pharmaceuticals, Inc.	Selective endothelin type-a antagonists

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DE69226813T2 (de) *	1991-06-07	1999-02-18	Ube Industries, Ltd., Ube, Yamaguchi	Pyrimidin- oder Triazin-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende Herbizide
DE4313412A1 (de) *	1993-04-23	1994-10-27	Basf Ag	3-(Het)aryl-Carbonsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung
DE4411225A1 (de) *	1994-03-31	1995-10-05	Basf Ag	Verwendung von Carbonsäurederivaten als Arzneimittel

1994
- 1994-03-31 DE DE4411225A patent/DE4411225A1/de not_active Withdrawn
1995
- 1995-03-09 HR HR950115A patent/HRP950115B1/xx not_active IP Right Cessation
- 1995-03-23 CN CN95193167A patent/CN1070701C/zh not_active Expired - Lifetime
- 1995-03-23 PT PT95914301T patent/PT752854E/pt unknown
- 1995-03-23 WO PCT/EP1995/001099 patent/WO1995026716A1/de active IP Right Grant
- 1995-03-23 SI SI9520048A patent/SI9520048A/sl unknown
- 1995-03-23 EP EP95914301A patent/EP0752854B1/de not_active Expired - Lifetime
- 1995-03-23 AU AU21356/95A patent/AU695193B2/en not_active Expired
- 1995-03-23 AT AT95914301T patent/ATE204471T1/de active
- 1995-03-23 DE DE59509537T patent/DE59509537D1/de not_active Expired - Lifetime
- 1995-03-23 UA UA96104109A patent/UA44734C2/uk unknown
- 1995-03-23 DK DK95914301T patent/DK0752854T3/da active
- 1995-03-23 JP JP52539195A patent/JP4001622B2/ja not_active Expired - Lifetime
- 1995-03-23 BR BR9507231A patent/BR9507231A/pt not_active Application Discontinuation
- 1995-03-23 ES ES95914301T patent/ES2162916T3/es not_active Expired - Lifetime
- 1995-03-23 RU RU96121628/14A patent/RU2163808C2/ru active
- 1995-03-23 NZ NZ283333A patent/NZ283333A/en not_active IP Right Cessation
- 1995-03-23 US US08/718,377 patent/US5840722A/en not_active Expired - Lifetime
- 1995-03-23 KR KR1019960705420A patent/KR100365629B1/ko not_active IP Right Cessation
- 1995-03-23 CZ CZ19962873A patent/CZ290684B6/cs not_active IP Right Cessation
- 1995-03-23 CA CA002186784A patent/CA2186784C/en not_active Expired - Lifetime
- 1995-03-23 PL PL95316563A patent/PL179580B1/pl unknown
- 1995-03-23 HU HU9602695A patent/HU228063B1/hu unknown
- 1995-03-27 IL IL11313795A patent/IL113137A/xx not_active IP Right Cessation
- 1995-03-28 TW TW084103012A patent/TW382594B/zh not_active IP Right Cessation
- 1995-03-30 ZA ZA952614A patent/ZA952614B/xx unknown
1996
- 1996-09-27 NO NO19964121A patent/NO310497B1/no not_active IP Right Cessation
- 1996-09-27 FI FI963885A patent/FI118589B/fi not_active IP Right Cessation
2001
- 2001-09-12 GR GR20010401467T patent/GR3036606T3/el unknown
2007
- 2007-02-15 JP JP2007034659A patent/JP4769742B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
KR100365629B1 (ko)	2003-04-10
MX9604448A (es)	1997-07-31
SI9520048A (en)	1997-02-28
DE59509537D1 (de)	2001-09-27
GR3036606T3 (en)	2001-12-31
EP0752854A1 (de)	1997-01-15
CA2186784C (en)	2007-02-20
IL113137A0 (en)	1995-06-29
ES2162916T3 (es)	2002-01-16
HRP950115B1 (en)	2001-12-31
CN1148807A (zh)	1997-04-30
PT752854E (pt)	2002-02-28
WO1995026716A1 (de)	1995-10-12
JP4769742B2 (ja)	2011-09-07
CZ287396A3 (en)	1997-04-16
EP0752854B1 (de)	2001-08-22
HRP950115A2 (en)	1997-10-31
ATE204471T1 (de)	2001-09-15
CN1070701C (zh)	2001-09-12
PL179580B1 (pl)	2000-09-29
JP2007131645A (ja)	2007-05-31
BR9507231A (pt)	1997-09-16
FI118589B (fi)	2008-01-15
FI963885A (fi)	1996-11-26
JP4001622B2 (ja)	2007-10-31
HUT75305A (en)	1997-05-28
FI963885A0 (fi)	1996-09-27
CZ290684B6 (cs)	2002-09-11
NO964121L (no)	1996-11-26
NZ283333A (en)	1997-02-24
AU2135695A (en)	1995-10-23
JPH09510984A (ja)	1997-11-04
UA44734C2 (uk)	2002-03-15
IL113137A (en)	1999-10-28
AU695193B2 (en)	1998-08-06
KR970702042A (ko)	1997-05-13
NO964121D0 (no)	1996-09-27
DK0752854T3 (da)	2001-10-08
RU2163808C2 (ru)	2001-03-10
CA2186784A1 (en)	1995-10-12
DE4411225A1 (de)	1995-10-05
HU228063B1 (en)	2012-09-28
TW382594B (en)	2000-02-21
ZA952614B (en)	1996-09-30
US5840722A (en)	1998-11-24
PL316563A1 (en)	1997-01-20
HU9602695D0 (en)	1996-11-28

Publication	Publication Date	Title
NO310497B1 (no)	2001-07-16	Pyrimidin- eller triazin-karboksylsyrederivater, hvilke kan anvendes som legemidler
ES2226996T3 (es)	2005-04-01	Nuevos derivados de acidos carboxilicos, su obtencion y empleo.
JPH0670021B2 (ja)	1994-09-07	医薬品としてのスルホンアミドの使用および新規スルホンアミド
KR20000068446A (ko)	2000-11-25	아지닐옥시, 및 페녹시-디아릴-카르복실산 유도체, 그의 제조 방법 및 혼합된 ｅｔａ/ｅｔｂ 엔도델린 수용체 길항물질로서의 용도
NO311801B1 (no)	2002-01-28	Nye hydroksykarboksylsyre-derivater og deres anvendelse
NO311802B1 (no)	2002-01-28	Nye karboksylsyre-derivater og deres anvendelse
TW426672B (en)	2001-03-21	Novel carboxylic acid derivatives, their preparation and use
CA2307770A1 (en)	1999-05-14	Novel carboxylic acid derivatives which carry amide side chains, production of said carboxylic acid derivatives and their use as endothelin receptor antagonists
TW546295B (en)	2003-08-11	Novel carboxylic acid derivatives, their preparation and use as mixed ETA/ETB receptor antagonists
CA2294050A1 (en)	1998-12-30	New .beta.-amino and .beta.-azidocarboxylic acid derivatives, the production thereof and the use thereof as endothelin receptor antagonists
SK11512000A3 (sk)	2001-04-09	5-substituované deriváty pyrimidín-2-yloxy karboxylových kyselín, ich príprava a ich využitie ako antagonistov endotelínu
JP2001523671A (ja)	2001-11-27	新規の置換α−ヒドロキシカルボン酸誘導体、その製造方法およびエンドセリンレセプターアンタゴニストとしての使用
AU765345B2 (en)	2003-09-18	Novel carboxylic acid derivatives comprising aryl-substituted nitrogen heterocycles, their production and their use as endothelin receptor antagonists
JP2002505324A (ja)	2002-02-19	不斉に置換された新規のカルボン酸誘導体、その製造方法ならびに混合ｅｔａ／ｅｔｂ受容体アンタゴニストとしての使用
CA2379545A1 (en)	2001-01-25	Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists
MXPA00007417A (en)	2001-07-03	Novel unsymmetrically substituted carboxylic acid derivatives, method for producing them, and their use as mixed eta
MXPA00006463A (en)	2001-07-03	5-substituted pyrimidine-2-yloxy carboxylic acid derivatives, the production of the same and their utilization as endothelin antagonists
CA2340167A1 (en)	2000-02-24	New carboxylic acid derivatives carrying keto side-chains, their production and their use as endothelin-receptor antagonists
CZ454399A3 (cs)	2000-04-12	Deriváty kyseliny β-amino a Bacidokarboxylové, způsob její výroby a její použití
CZ326198A3 (cs)	2000-01-12	Nové deriváty alfa-hydroxy kyseliny, jejich příprava a použití
MXPA98008197A (en)	1999-04-06	Derivatives of novel carboxylic acids, its preparation and its
CZ20002963A3 (cs)	2000-11-15	Nové deriváty karboxylové kyseliny, obsahující 5- substituovaný pyrimidinový kruh, jejich příprava a použiti

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Date	Code	Title	Description
2014-06-02	CHAD	Change of the owner's name or address (par. 44 patent law, par. patentforskriften)	Owner name: ABBVIE DEUTSCHLAND GMBH & CO AG, DE
2015-03-30	MK1K	Patent expired