DE19933164A1 - Neue Carbonsäurederivate mit 5,6 substituiertem Pyrimidinring, ihre Herstellung und Verwendung als Endothelin Rezeptorantagonisten - Google Patents
Neue Carbonsäurederivate mit 5,6 substituiertem Pyrimidinring, ihre Herstellung und Verwendung als Endothelin RezeptorantagonistenInfo
- Publication number
- DE19933164A1 DE19933164A1 DE19933164A DE19933164A DE19933164A1 DE 19933164 A1 DE19933164 A1 DE 19933164A1 DE 19933164 A DE19933164 A DE 19933164A DE 19933164 A DE19933164 A DE 19933164A DE 19933164 A1 DE19933164 A1 DE 19933164A1
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- alkoxy
- phenyl
- alkylthio
- haloalkyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 229940118365 Endothelin receptor antagonist Drugs 0.000 title claims description 6
- 239000002308 endothelin receptor antagonist Substances 0.000 title claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 46
- -1 C 1 -C 4 alkyl Chemical group 0.000 claims description 76
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 33
- 150000003254 radicals Chemical class 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 27
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 25
- 108050009340 Endothelin Proteins 0.000 claims description 18
- 102000002045 Endothelin Human genes 0.000 claims description 18
- 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 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 5
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 4
- 125000004450 alkenylene group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 4
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 4
- FONOSWYYBCBQGN-UHFFFAOYSA-N ethylene dione Chemical group O=C=C=O FONOSWYYBCBQGN-UHFFFAOYSA-N 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000003536 tetrazoles Chemical class 0.000 claims description 3
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 2
- 229940123413 Angiotensin II antagonist Drugs 0.000 claims description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 2
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- 208000033626 Renal failure acute Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 201000011040 acute kidney failure Diseases 0.000 claims description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 229940030606 diuretics Drugs 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 239000002461 renin inhibitor Substances 0.000 claims description 2
- 230000036454 renin-angiotensin system Effects 0.000 claims description 2
- 229940086526 renin-inhibitors Drugs 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 6
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 claims 3
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims 3
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims 3
- 102000003729 Neprilysin Human genes 0.000 claims 2
- 108090000028 Neprilysin Proteins 0.000 claims 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 2
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 239000000480 calcium channel blocker Substances 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 239000011162 core material Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000008186 active pharmaceutical agent Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 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 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 101800004490 Endothelin-1 Proteins 0.000 description 4
- 102100033902 Endothelin-1 Human genes 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
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- 239000004480 active ingredient Substances 0.000 description 4
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- 239000000872 buffer Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FXTPUVLWVRTMHV-UHFFFAOYSA-N 2-(4-methoxy-5-methylpyrimidin-2-yl)oxy-3,3-diphenyl-3-phenylmethoxypropanoic acid Chemical compound C1=C(C)C(OC)=NC(OC(C(O)=O)C(OCC=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 FXTPUVLWVRTMHV-UHFFFAOYSA-N 0.000 description 3
- RCJNDDNXUYCUOY-UHFFFAOYSA-N 2-chloro-4-methoxy-5-methylpyrimidine Chemical compound COC1=NC(Cl)=NC=C1C RCJNDDNXUYCUOY-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000010180 Endothelin receptor Human genes 0.000 description 3
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- 208000001647 Renal Insufficiency Diseases 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
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- CAWPKIJTHPMICR-GOSISDBHSA-N (2s)-3-methoxy-2-(4-methoxy-5-methylpyrimidin-2-yl)oxy-3,3-diphenylpropanoic acid Chemical compound C1=C(C)C(OC)=NC(O[C@H](C(O)=O)C(OC)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 CAWPKIJTHPMICR-GOSISDBHSA-N 0.000 description 2
- MFDUCCDTBLZMSZ-UHFFFAOYSA-N 2-(4-methoxy-5-methylpyrimidin-2-yl)oxy-3,3-diphenyl-3-propan-2-yloxypropanoic acid Chemical compound C1=C(C)C(OC)=NC(OC(C(O)=O)C(OC(C)C)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 MFDUCCDTBLZMSZ-UHFFFAOYSA-N 0.000 description 2
- JDOXCEWQNADMCF-UHFFFAOYSA-N 2-(6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropanoic acid Chemical compound COC(C(Oc1ncc2CCCc2n1)C(O)=O)(c1ccccc1)c1ccccc1 JDOXCEWQNADMCF-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- IFQZZMKLFMUHRW-UHFFFAOYSA-N 2-methylsulfanyl-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound CSC1=NC=C2CCCC2=N1 IFQZZMKLFMUHRW-UHFFFAOYSA-N 0.000 description 2
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- OQAWIDVMPODGCQ-UHFFFAOYSA-N 3,3-bis(4-fluorophenyl)-3-methoxy-2-(4-methoxy-5-methylpyrimidin-2-yl)oxypropanoic acid Chemical compound C1=C(C)C(OC)=NC(OC(C(O)=O)C(OC)(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=N1 OQAWIDVMPODGCQ-UHFFFAOYSA-N 0.000 description 2
- QCMKYULRXYPSTG-UHFFFAOYSA-N 3-[(3,4-dimethylphenyl)methoxy]-2-(4-methoxy-5-methylpyrimidin-2-yl)oxy-3,3-diphenylpropanoic acid Chemical compound C1=C(C)C(OC)=NC(OC(C(O)=O)C(OCC=2C=C(C)C(C)=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 QCMKYULRXYPSTG-UHFFFAOYSA-N 0.000 description 2
- SXNOYFOYXGVZDE-UHFFFAOYSA-N 3-[2-(3,4-dimethoxyphenyl)ethoxy]-2-(9-methylpurin-2-yl)oxy-3,3-diphenylpropanoic acid Chemical compound COc1ccc(CCOC(C(Oc2ncc3ncn(C)c3n2)C(O)=O)(c2ccccc2)c2ccccc2)cc1OC SXNOYFOYXGVZDE-UHFFFAOYSA-N 0.000 description 2
- QGPPVJOASIAFMG-UHFFFAOYSA-N 3-ethoxy-2-(4-methoxy-5-methylpyrimidin-2-yl)oxy-3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCC)C(C(O)=O)OC1=NC=C(C)C(OC)=N1 QGPPVJOASIAFMG-UHFFFAOYSA-N 0.000 description 2
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- FJFJLOMVXWGBDU-UHFFFAOYSA-N 4-methoxy-5-methyl-2-methylsulfonylpyrimidine Chemical compound COC1=NC(S(C)(=O)=O)=NC=C1C FJFJLOMVXWGBDU-UHFFFAOYSA-N 0.000 description 2
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
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- 201000008806 mesenchymal cell neoplasm Diseases 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 210000000885 nephron Anatomy 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000009871 nonspecific binding Effects 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
- 239000002674 ointment Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical group 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- 238000005690 transetherification reaction Methods 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
-
- 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
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
-
- 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
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
- A61P5/16—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4 for decreasing, blocking or antagonising the activity of the thyroid hormones
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
Priority Applications (21)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19933164A DE19933164A1 (de) | 1999-07-20 | 1999-07-20 | Neue Carbonsäurederivate mit 5,6 substituiertem Pyrimidinring, ihre Herstellung und Verwendung als Endothelin Rezeptorantagonisten |
| PCT/EP2000/006293 WO2001005771A1 (de) | 1999-07-20 | 2000-07-05 | Neue carbonsäurederivate mit 5,6 substituiertem pyrimidinring, ihre herstellung und verwendung als endothelin rezeptorantagonisten |
| BR0012592-0A BR0012592A (pt) | 1999-07-20 | 2000-07-05 | Composto, uso dos compostos, combinação, e, preparação farmacêutica para uso oral ou parenteral |
| AU65615/00A AU6561500A (en) | 1999-07-20 | 2000-07-05 | Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists |
| PL00353165A PL353165A1 (en) | 1999-07-20 | 2000-07-05 | Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists |
| MXPA02000616A MXPA02000616A (es) | 1999-07-20 | 2000-07-05 | Derivados de acidos carboxilicos, novedosos, con anillo pirimidina sustituido en las posiciones 5, 6, su preparacion y uso como antagonistas de los receptores para endotelina. |
| CN00810533A CN1367778A (zh) | 1999-07-20 | 2000-07-05 | 新型的具有5,6取代嘧啶环的羧酸衍生物、其制备方法和作为内皮素受体拮抗药的用途 |
| HU0202646A HUP0202646A3 (en) | 1999-07-20 | 2000-07-05 | Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof for producing endothelin receptor antagonists and pharmaceutical compositions containing the compounds |
| KR1020027000815A KR20020019550A (ko) | 1999-07-20 | 2000-07-05 | 5,6-치환된 피리미딘 고리를 포함하는 신규 카르복실산유도체, 그의 제조 방법 및 엔도텔린 수용체 길항제로서의그의 용도 |
| SK77-2002A SK772002A3 (en) | 1999-07-20 | 2000-07-05 | Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists |
| TR2002/00622T TR200200622T2 (cs) | 1999-07-20 | 2000-07-05 | |
| EP00953009A EP1196394A1 (de) | 1999-07-20 | 2000-07-05 | Neue carbonsäurederivate mit 5,6 substituiertem pyrimidinring, ihre herstellung und verwendung als endothelin rezeptorantagonisten |
| CZ2002190A CZ2002190A3 (cs) | 1999-07-20 | 2000-07-05 | Nové deriváty karboxylové kyseliny s 5,6-substituovaným pyrimidinovým kruhem, způsob jejich přípravy a použití jako antagonistů receptoru endothelinu |
| JP2001511432A JP2003505377A (ja) | 1999-07-20 | 2000-07-05 | ５，６−置換されたピリミジン環を有する新規のカルボン酸誘導体、その製造およびエンドセリン受容体アンタゴニストとしてのその使用 |
| IL14766600A IL147666A0 (en) | 1999-07-20 | 2000-07-05 | Novel carboxylic acid derivatives with 5, 6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists |
| CA002379545A CA2379545A1 (en) | 1999-07-20 | 2000-07-05 | Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists |
| TW089113992A TW555749B (en) | 1999-07-20 | 2000-07-13 | Novel carboxylic acid derivatives with 4,5-substituted pyrimidine ring, their preparation and pharmaceutical preparation comprising the same |
| ARP000103661A AR030026A1 (es) | 1999-07-20 | 2000-07-17 | Nuevos derivados de acidos carboxilicos con anillo de pirimidina 5,6-sustituido, su uso para preparar medicamentos y combinaciones y preparados farmaceuticos que los comprenden |
| ZA200200333A ZA200200333B (en) | 1999-07-20 | 2002-01-15 | Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists. |
| NO20020254A NO20020254L (no) | 1999-07-20 | 2002-01-17 | Nye karboksylsyrederivater med 5,6-substituert pyrimidinring, fremstilling og anvendelse derav som endotelinreseptor-antagonister |
| BG106321A BG106321A (en) | 1999-07-20 | 2002-01-18 | Novel carboxylic acid derivatives with 5,6- substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19933164A DE19933164A1 (de) | 1999-07-20 | 1999-07-20 | Neue Carbonsäurederivate mit 5,6 substituiertem Pyrimidinring, ihre Herstellung und Verwendung als Endothelin Rezeptorantagonisten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19933164A1 true DE19933164A1 (de) | 2001-01-25 |
Family
ID=7914884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19933164A Withdrawn DE19933164A1 (de) | 1999-07-20 | 1999-07-20 | Neue Carbonsäurederivate mit 5,6 substituiertem Pyrimidinring, ihre Herstellung und Verwendung als Endothelin Rezeptorantagonisten |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1196394A1 (cs) |
| JP (1) | JP2003505377A (cs) |
| KR (1) | KR20020019550A (cs) |
| CN (1) | CN1367778A (cs) |
| AR (1) | AR030026A1 (cs) |
| AU (1) | AU6561500A (cs) |
| BG (1) | BG106321A (cs) |
| BR (1) | BR0012592A (cs) |
| CA (1) | CA2379545A1 (cs) |
| CZ (1) | CZ2002190A3 (cs) |
| DE (1) | DE19933164A1 (cs) |
| HU (1) | HUP0202646A3 (cs) |
| IL (1) | IL147666A0 (cs) |
| MX (1) | MXPA02000616A (cs) |
| NO (1) | NO20020254L (cs) |
| PL (1) | PL353165A1 (cs) |
| SK (1) | SK772002A3 (cs) |
| TR (1) | TR200200622T2 (cs) |
| TW (1) | TW555749B (cs) |
| WO (1) | WO2001005771A1 (cs) |
| ZA (1) | ZA200200333B (cs) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2575000T3 (es) * | 2009-07-10 | 2016-06-23 | Cadila Healthcare Limited | Proceso mejorado para la preparación de ambrisentano |
| KR20130054250A (ko) | 2010-03-15 | 2013-05-24 | 낫코 파마 리미티드 | 매우 순수한 암브리센탄의 제조를 위한 방법 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19636046A1 (de) * | 1996-09-05 | 1998-03-12 | Basf Ag | Neue Carbonsäurederivate, ihre Herstellung und Verwendung als gemischte ET¶A¶/ET¶B¶-Rezeptorantagonisten |
| PL340871A1 (en) * | 1997-10-31 | 2001-03-12 | Basf Ag | Novel derivatives of carboxylic with admidic side chains, method of obtaining them and application of such novel derivatives as antagonists of endothelin rceptors |
-
1999
- 1999-07-20 DE DE19933164A patent/DE19933164A1/de not_active Withdrawn
-
2000
- 2000-07-05 AU AU65615/00A patent/AU6561500A/en not_active Abandoned
- 2000-07-05 MX MXPA02000616A patent/MXPA02000616A/es unknown
- 2000-07-05 PL PL00353165A patent/PL353165A1/xx not_active Application Discontinuation
- 2000-07-05 TR TR2002/00622T patent/TR200200622T2/xx unknown
- 2000-07-05 JP JP2001511432A patent/JP2003505377A/ja not_active Abandoned
- 2000-07-05 WO PCT/EP2000/006293 patent/WO2001005771A1/de not_active Ceased
- 2000-07-05 EP EP00953009A patent/EP1196394A1/de not_active Withdrawn
- 2000-07-05 CZ CZ2002190A patent/CZ2002190A3/cs unknown
- 2000-07-05 CA CA002379545A patent/CA2379545A1/en not_active Abandoned
- 2000-07-05 IL IL14766600A patent/IL147666A0/xx unknown
- 2000-07-05 SK SK77-2002A patent/SK772002A3/sk unknown
- 2000-07-05 HU HU0202646A patent/HUP0202646A3/hu unknown
- 2000-07-05 KR KR1020027000815A patent/KR20020019550A/ko not_active Ceased
- 2000-07-05 BR BR0012592-0A patent/BR0012592A/pt not_active IP Right Cessation
- 2000-07-05 CN CN00810533A patent/CN1367778A/zh active Pending
- 2000-07-13 TW TW089113992A patent/TW555749B/zh active
- 2000-07-17 AR ARP000103661A patent/AR030026A1/es unknown
-
2002
- 2002-01-15 ZA ZA200200333A patent/ZA200200333B/en unknown
- 2002-01-17 NO NO20020254A patent/NO20020254L/no not_active Application Discontinuation
- 2002-01-18 BG BG106321A patent/BG106321A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1367778A (zh) | 2002-09-04 |
| ZA200200333B (en) | 2003-04-30 |
| AR030026A1 (es) | 2003-08-13 |
| BG106321A (en) | 2002-08-30 |
| IL147666A0 (en) | 2002-08-14 |
| MXPA02000616A (es) | 2002-08-30 |
| JP2003505377A (ja) | 2003-02-12 |
| TW555749B (en) | 2003-10-01 |
| CA2379545A1 (en) | 2001-01-25 |
| NO20020254L (no) | 2002-02-20 |
| TR200200622T2 (cs) | 2002-06-21 |
| KR20020019550A (ko) | 2002-03-12 |
| NO20020254D0 (no) | 2002-01-17 |
| PL353165A1 (en) | 2003-10-20 |
| CZ2002190A3 (cs) | 2003-08-13 |
| HUP0202646A2 (hu) | 2003-02-28 |
| SK772002A3 (en) | 2003-01-09 |
| WO2001005771A1 (de) | 2001-01-25 |
| AU6561500A (en) | 2001-02-05 |
| BR0012592A (pt) | 2002-05-28 |
| HUP0202646A3 (en) | 2003-03-28 |
| EP1196394A1 (de) | 2002-04-17 |
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| 8127 | New person/name/address of the applicant |
Owner name: ABBOTT GMBH & CO. KG, 65205 WIESBADEN, DE |
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| 8139 | Disposal/non-payment of the annual fee |