HRP20000602A2 - 5-substituted pyrimidine-2-yloxy carboxylic acid derivatives, the production of the same and their utilization as endothelin antagonists - Google Patents
5-substituted pyrimidine-2-yloxy carboxylic acid derivatives, the production of the same and their utilization as endothelin antagonists Download PDFInfo
- Publication number
- HRP20000602A2 HRP20000602A2 HR20000602A HRP20000602A HRP20000602A2 HR P20000602 A2 HRP20000602 A2 HR P20000602A2 HR 20000602 A HR20000602 A HR 20000602A HR P20000602 A HRP20000602 A HR P20000602A HR P20000602 A2 HRP20000602 A2 HR P20000602A2
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- Prior art keywords
- alkyl
- alkoxy
- alkylthio
- halogen
- haloalkyl
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- -1 5-substituted pyrimidine-2-yloxy carboxylic acid Chemical class 0.000 title claims description 77
- 102000002045 Endothelin Human genes 0.000 title claims description 21
- 108050009340 Endothelin Proteins 0.000 title claims description 21
- 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 title claims description 21
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 239000005557 antagonist Substances 0.000 title description 7
- 150000003254 radicals Chemical class 0.000 claims description 39
- 150000001875 compounds Chemical class 0.000 claims description 38
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 37
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 35
- 150000002367 halogens Chemical class 0.000 claims description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 239000011593 sulfur 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
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 8
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 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 description 6
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims description 6
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
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- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 5
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 5
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- 239000013543 active substance Substances 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- FONOSWYYBCBQGN-UHFFFAOYSA-N ethylene dione Chemical group O=C=C=O FONOSWYYBCBQGN-UHFFFAOYSA-N 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-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
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 4
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- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
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- 208000012998 acute renal failure Diseases 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims description 2
- 239000002876 beta blocker Substances 0.000 claims description 2
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 230000002685 pulmonary effect Effects 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
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- 229940086526 renin-inhibitors Drugs 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 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 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims 4
- 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
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- 239000002981 blocking agent Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 238000012360 testing method Methods 0.000 description 11
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- 125000001424 substituent group Chemical group 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 102100033902 Endothelin-1 Human genes 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
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- 238000000034 method Methods 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
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- 101800004490 Endothelin-1 Proteins 0.000 description 4
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- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical group FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 4
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- 238000005160 1H NMR spectroscopy Methods 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
- 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
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 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 3
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
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- 238000002844 melting Methods 0.000 description 3
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- 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- FQXMSHCCFXLEFK-UHFFFAOYSA-N 2-(5-fluoro-4-morpholin-4-ylpyrimidin-2-yl)oxy-3-methoxy-3,3-diphenylpropanoic acid Chemical compound O1CCN(CC1)C1=NC(=NC=C1F)OC(C(=O)O)C(C1=CC=CC=C1)(C1=CC=CC=C1)OC FQXMSHCCFXLEFK-UHFFFAOYSA-N 0.000 description 2
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- CMMXCVYESRODNH-UHFFFAOYSA-N trichloroepoxyethane Chemical class ClC1OC1(Cl)Cl CMMXCVYESRODNH-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 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
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- 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
- 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
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- 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
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19806438A DE19806438A1 (de) | 1998-02-17 | 1998-02-17 | Neue Carbonsäurederivate mit 5-substituiertem Pyrimidinring, ihre Herstellung und Verwendung |
| PCT/EP1999/000776 WO1999042453A1 (de) | 1998-02-17 | 1999-02-05 | 5-substituierte pyrimidin-2-yloxy-carbonsäurederivate, deren herstellung und deren verwendung als endothelin-antagonisten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20000602A2 true HRP20000602A2 (en) | 2001-06-30 |
Family
ID=7857948
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20000602A HRP20000602A2 (en) | 1998-02-17 | 2000-09-13 | 5-substituted pyrimidine-2-yloxy carboxylic acid derivatives, the production of the same and their utilization as endothelin antagonists |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP1066268A1 (tr) |
| JP (1) | JP2002503726A (tr) |
| KR (1) | KR20010086247A (tr) |
| CN (1) | CN1291190A (tr) |
| AR (1) | AR014960A1 (tr) |
| AU (1) | AU3027199A (tr) |
| BG (1) | BG104577A (tr) |
| BR (1) | BR9907911A (tr) |
| CA (1) | CA2321182A1 (tr) |
| DE (1) | DE19806438A1 (tr) |
| HR (1) | HRP20000602A2 (tr) |
| HU (1) | HUP0100957A3 (tr) |
| IL (1) | IL137038A0 (tr) |
| NO (1) | NO20004075D0 (tr) |
| PL (1) | PL342311A1 (tr) |
| SK (1) | SK11512000A3 (tr) |
| TR (1) | TR200002376T2 (tr) |
| TW (1) | TW579376B (tr) |
| WO (1) | WO1999042453A1 (tr) |
| ZA (1) | ZA991214B (tr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19924892A1 (de) * | 1999-06-01 | 2000-12-07 | Basf Ag | Neue Carbonsäurederivate mit arylsubstituierten Stickstoffheterocyclen, ihre Herstellung und Verwendung als Endothelin Rezeptorantagonisten |
| US8217155B2 (en) | 2007-07-31 | 2012-07-10 | Gilead Colorado, Inc. | Metabolites and derivatives of ambrisentan |
| JP5749017B2 (ja) | 2008-01-22 | 2015-07-15 | ダウ アグロサイエンシィズ エルエルシー | ５−フルオロピリミジン誘導体 |
| EP2317851B1 (en) * | 2008-08-01 | 2014-01-15 | Dow AgroSciences LLC | Use of 5-fluorocytosine as a fungicide |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| DE19614534A1 (de) * | 1996-04-12 | 1997-10-16 | Basf Ag | Neue Carbonsäurederivate, ihre Herstellung und Verwendung |
| DE19614533A1 (de) * | 1996-04-12 | 1997-10-16 | Basf Ag | Neue alpha-Hydroxysäurederivate, ihre Herstellung und Verwendung |
| CN1247533A (zh) * | 1996-12-18 | 2000-03-15 | Basf公司 | 杂环羧酸衍生物,它们的制备方法和它们作为内皮素(endothelin)受体拮抗剂的用途 |
| DE19726146A1 (de) * | 1997-06-19 | 1998-12-24 | Basf Ag | Neue ß-Amino und ß-Azidopcarbonsäurederivate, ihre Herstellung und Verwendung als Endothelinrezeptorantagonisten |
| BR9814951A (pt) * | 1997-10-31 | 2000-10-03 | Basf Ag | Derivado de ácido carboxìlico, uso do mesmo, preparação de medicamento para o uso oral, parenteral, combinação, uso de compostos, fragmento estrutural, uso do mesmo, antagonista de receptor de endotelina, e, composto |
-
1998
- 1998-02-17 DE DE19806438A patent/DE19806438A1/de not_active Withdrawn
-
1999
- 1999-02-05 BR BR9907911-9A patent/BR9907911A/pt not_active IP Right Cessation
- 1999-02-05 PL PL99342311A patent/PL342311A1/xx unknown
- 1999-02-05 SK SK1151-2000A patent/SK11512000A3/sk unknown
- 1999-02-05 WO PCT/EP1999/000776 patent/WO1999042453A1/de not_active Application Discontinuation
- 1999-02-05 JP JP2000532405A patent/JP2002503726A/ja active Pending
- 1999-02-05 HU HU0100957A patent/HUP0100957A3/hu unknown
- 1999-02-05 CN CN99803037A patent/CN1291190A/zh active Pending
- 1999-02-05 IL IL13703899A patent/IL137038A0/xx unknown
- 1999-02-05 AU AU30271/99A patent/AU3027199A/en not_active Abandoned
- 1999-02-05 CA CA002321182A patent/CA2321182A1/en not_active Abandoned
- 1999-02-05 EP EP99911657A patent/EP1066268A1/de not_active Withdrawn
- 1999-02-05 TR TR2000/02376T patent/TR200002376T2/tr unknown
- 1999-02-05 KR KR1020007008925A patent/KR20010086247A/ko not_active Application Discontinuation
- 1999-02-10 TW TW088102031A patent/TW579376B/zh active
- 1999-02-16 ZA ZA9901214A patent/ZA991214B/xx unknown
- 1999-02-16 AR ARP990100634A patent/AR014960A1/es not_active Application Discontinuation
-
2000
- 2000-07-04 BG BG104577A patent/BG104577A/bg unknown
- 2000-08-15 NO NO20004075A patent/NO20004075D0/no not_active Application Discontinuation
- 2000-09-13 HR HR20000602A patent/HRP20000602A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CN1291190A (zh) | 2001-04-11 |
| AR014960A1 (es) | 2001-04-11 |
| JP2002503726A (ja) | 2002-02-05 |
| AU3027199A (en) | 1999-09-06 |
| TW579376B (en) | 2004-03-11 |
| HUP0100957A3 (en) | 2002-03-28 |
| PL342311A1 (en) | 2001-06-04 |
| HUP0100957A2 (hu) | 2002-02-28 |
| BR9907911A (pt) | 2000-10-24 |
| IL137038A0 (en) | 2001-06-14 |
| ZA991214B (en) | 2000-08-16 |
| WO1999042453A1 (de) | 1999-08-26 |
| CA2321182A1 (en) | 1999-08-26 |
| NO20004075L (no) | 2000-08-15 |
| EP1066268A1 (de) | 2001-01-10 |
| KR20010086247A (ko) | 2001-09-10 |
| DE19806438A1 (de) | 1999-08-19 |
| NO20004075D0 (no) | 2000-08-15 |
| TR200002376T2 (tr) | 2000-12-21 |
| SK11512000A3 (sk) | 2001-04-09 |
| BG104577A (bg) | 2001-03-30 |
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Legal Events
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|---|---|---|---|
| A1OB | Publication of a patent application | ||
| ARAI | Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application | ||
| OBST | Application withdrawn |