AU748610B2 - Novel carboxylic acid derivatives, their production and their their use as mixed ETa/ETb endothelin-receptor antagonists - Google Patents

Novel carboxylic acid derivatives, their production and their their use as mixed ETa/ETb endothelin-receptor antagonists Download PDF

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Publication number: AU748610B2
Authority: AU; Australia
Prior art keywords: phenyl; cooh; alkyl; ome; diome
Prior art date: 1997-09-04
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.): Ceased

Application number

AU95333/98A

Other languages

English (en)

Other versions

AU9533398A (en

Inventor

Wilhelm Amberg

Stefan Hergenroder

Rolf Jansen

Dagmar Klinge

Manfred Raschack

Hartmut Riechers

Liliane Unger

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

BASF SE

Original Assignee

BASF SE

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.)

1997-09-04

Filing date

1998-08-24

Publication date

2002-06-06

1997-09-04 Priority claimed from DE19738578A external-priority patent/DE19738578A1/de

1998-03-18 Priority claimed from DE1998111915 external-priority patent/DE19811915A1/de

1998-08-24 Application filed by BASF SE filed Critical BASF SE

1999-03-22 Publication of AU9533398A publication Critical patent/AU9533398A/en

2002-06-06 Application granted granted Critical

2002-06-06 Publication of AU748610B2 publication Critical patent/AU748610B2/en

2018-08-24 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

150000001732 carboxylic acid derivatives Chemical class 0.000 title claims description 14
229940118365 Endothelin receptor antagonist Drugs 0.000 title description 2
239000002308 endothelin receptor antagonist Substances 0.000 title description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 134
-1 mercapto, carboxyl Chemical group 0.000 claims description 78
229910052739 hydrogen Inorganic materials 0.000 claims description 64
229910052736 halogen Inorganic materials 0.000 claims description 31
150000002367 halogens Chemical class 0.000 claims description 31
150000003254 radicals Chemical class 0.000 claims description 23
229910052717 sulfur Inorganic materials 0.000 claims description 20
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
125000004093 cyano group Chemical group *C#N 0.000 claims description 14
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
229910052760 oxygen Inorganic materials 0.000 claims description 14
239000011593 sulfur Substances 0.000 claims description 14
102100040611 Endothelin receptor type B Human genes 0.000 claims description 12
150000002431 hydrogen Chemical class 0.000 claims description 12
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 11
239000001301 oxygen Substances 0.000 claims description 11
125000001624 naphthyl group Chemical group 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
229910052783 alkali metal Inorganic materials 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 7
150000001340 alkali metals Chemical class 0.000 claims description 6
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 6
150000001768 cations Chemical class 0.000 claims description 6
125000001072 heteroaryl group Chemical group 0.000 claims description 6
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
125000004430 oxygen atom Chemical group O* 0.000 claims description 6
150000001342 alkaline earth metals Chemical class 0.000 claims description 5
125000002947 alkylene group Chemical group 0.000 claims description 5
125000005466 alkylenyl group Chemical group 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
229940079593 drug Drugs 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
150000003839 salts Chemical class 0.000 claims description 4
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000004450 alkenylene group Chemical group 0.000 claims description 3
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 3
239000002464 receptor antagonist Substances 0.000 claims description 3
229940044551 receptor antagonist Drugs 0.000 claims description 3
125000004434 sulfur atom Chemical group 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 2
150000005840 aryl radicals Chemical class 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 3
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 3
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims 2
101100496114 Caenorhabditis elegans clc-2 gene Proteins 0.000 claims 2
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 114
125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 45
150000001875 compounds Chemical class 0.000 description 29
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 29
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
239000002253 acid Substances 0.000 description 13
239000000203 mixture Substances 0.000 description 13
239000002904 solvent Substances 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
238000002844 melting Methods 0.000 description 12
230000008018 melting Effects 0.000 description 12
108050009340 Endothelin Proteins 0.000 description 11
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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 11
238000005160 1H NMR spectroscopy Methods 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
102000005962 receptors Human genes 0.000 description 9
108020003175 receptors Proteins 0.000 description 9
238000012360 testing method Methods 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
238000006243 chemical reaction Methods 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
239000005557 antagonist Substances 0.000 description 6
239000002585 base Substances 0.000 description 6
230000027455 binding Effects 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
239000000243 solution Substances 0.000 description 6
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
230000036772 blood pressure Effects 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
101150041968 CDC13 gene Proteins 0.000 description 4
101800004490 Endothelin-1 Proteins 0.000 description 4
102100033902 Endothelin-1 Human genes 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
239000000872 buffer Substances 0.000 description 4
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
239000005457 ice water Substances 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
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
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
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206010020772 Hypertension Diseases 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
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
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150000001735 carboxylic acids Chemical class 0.000 description 3
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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 description 2
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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
- C07D239/52—Two oxygen atoms
- 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
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/70—One oxygen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- 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
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/36—One oxygen atom
- C07D263/38—One oxygen atom attached in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/44—Two oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Peptides Or Proteins (AREA)
Thiazole And Isothizaole Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

AU95333/98A 1997-09-04 1998-08-24 Novel carboxylic acid derivatives, their production and their their use as mixed ETa/ETb endothelin-receptor antagonists Ceased AU748610B2 (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
DE19738578		1997-09-04
DE19738578A DE19738578A1 (de)	1997-09-04	1997-09-04	Neue Carbonsäurederivate, ihre Herstellung und Verwendung als gemischte ET¶A¶/ET¶B¶-Rezeptorantagonisten
DE1998111915 DE19811915A1 (de)	1998-03-18	1998-03-18	Neue Carbonsäurederivate, ihre Herstellung und Verwendung als gemischte ET¶A¶/ET¶B¶-Rezeptorantagonisten
DE19811915		1998-03-18
PCT/EP1998/005354 WO1999011629A1 (fr)	1997-09-04	1998-08-24	Nouveaux derives d'acide carboxylique, leur production et leur utilisation comme antagonistes mixtes des recepteurs d'endotheline eta et et¿b?

Publications (2)

Publication Number	Publication Date
AU9533398A AU9533398A (en)	1999-03-22
AU748610B2 true AU748610B2 (en)	2002-06-06

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ID=26039663

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Application Number	Title	Priority Date	Filing Date
AU95333/98A Ceased AU748610B2 (en)	1997-09-04	1998-08-24	Novel carboxylic acid derivatives, their production and their their use as mixed ETa/ETb endothelin-receptor antagonists

Country Status (21)

Country	Link
EP (1)	EP1009741A1 (fr)
JP (1)	JP2001514254A (fr)
KR (1)	KR20010023615A (fr)
CN (1)	CN1269792A (fr)
AR (1)	AR017052A1 (fr)
AU (1)	AU748610B2 (fr)
BG (1)	BG104222A (fr)
BR (1)	BR9811631A (fr)
CA (1)	CA2302350A1 (fr)
CO (1)	CO4970738A1 (fr)
HR (1)	HRP980484A2 (fr)
HU (1)	HUP0004935A3 (fr)
ID (1)	ID25620A (fr)
IL (1)	IL134276A0 (fr)
NO (1)	NO20001077D0 (fr)
NZ (1)	NZ502660A (fr)
PL (1)	PL338954A1 (fr)
SK (1)	SK1522000A3 (fr)
TR (1)	TR200000602T2 (fr)
TW (1)	TW546295B (fr)
WO (1)	WO1999011629A1 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
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DE19924892A1 (de) *	1999-06-01	2000-12-07	Basf Ag	Neue Carbonsäurederivate mit arylsubstituierten Stickstoffheterocyclen, ihre Herstellung und Verwendung als Endothelin Rezeptorantagonisten
US20090263472A1 (en) *	2006-05-29	2009-10-22	Nicox S.A.	Endothelin receptor antagonist derivatives
RU2010140442A (ru)	2008-03-05	2012-04-10	Бёрингер Ингельхайм Интернациональ Гмбх (De)	Трициклические производные пиридина, лекарственные средства, содержащие такие соединения, их применение и способ их получения
JP5531097B2 (ja) *	2009-07-10	2014-06-25	カディラ・ヘルスケア・リミテッド	アンブリセンタンを調製するための改善された方法およびその新規な中間体
MA34007B1 (fr)	2010-02-19	2013-02-01	Boehringer Ingelheim Int	Derives de pyridine tricycliques medicaments contenant ces composes leur utilisation et leur procede de preparation
JP5947382B2 (ja)	2011-08-17	2016-07-06	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	フロ［３，４−ｃ］キノリン誘導体、このような化合物を含む薬物、それらの使用及びそれらの調製方法

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* Cited by examiner, † Cited by third party
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
US6136828A (en) *	1996-02-01	2000-10-24	Smithkline Beecham Corporation	Endothelin receptor antagonists
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

1998
- 1998-08-24 WO PCT/EP1998/005354 patent/WO1999011629A1/fr not_active Application Discontinuation
- 1998-08-24 CA CA002302350A patent/CA2302350A1/fr not_active Abandoned
- 1998-08-24 SK SK152-2000A patent/SK1522000A3/sk unknown
- 1998-08-24 NZ NZ502660A patent/NZ502660A/en unknown
- 1998-08-24 HU HU0004935A patent/HUP0004935A3/hu unknown
- 1998-08-24 PL PL98338954A patent/PL338954A1/xx unknown
- 1998-08-24 BR BR9811631-2A patent/BR9811631A/pt not_active IP Right Cessation
- 1998-08-24 ID IDW20000386D patent/ID25620A/id unknown
- 1998-08-24 CN CN98808862A patent/CN1269792A/zh active Pending
- 1998-08-24 KR KR1020007002264A patent/KR20010023615A/ko not_active Withdrawn
- 1998-08-24 TR TR2000/00602T patent/TR200000602T2/xx unknown
- 1998-08-24 IL IL13427698A patent/IL134276A0/xx unknown
- 1998-08-24 AU AU95333/98A patent/AU748610B2/en not_active Ceased
- 1998-08-24 JP JP2000508669A patent/JP2001514254A/ja active Pending
- 1998-08-24 EP EP98948859A patent/EP1009741A1/fr not_active Withdrawn
- 1998-09-02 HR HR19811915.1A patent/HRP980484A2/hr not_active Application Discontinuation
- 1998-09-03 CO CO98050561A patent/CO4970738A1/es unknown
- 1998-09-03 AR ARP980104402A patent/AR017052A1/es not_active Application Discontinuation
- 1998-09-03 TW TW087114595A patent/TW546295B/zh active
2000
- 2000-03-02 NO NO20001077A patent/NO20001077D0/no not_active Application Discontinuation
- 2000-03-06 BG BG104222A patent/BG104222A/xx unknown

Also Published As

Publication number	Publication date
AR017052A1 (es)	2001-08-22
HUP0004935A2 (hu)	2001-10-28
CN1269792A (zh)	2000-10-11
BR9811631A (pt)	2000-09-26
NO20001077L (no)	2000-03-02
WO1999011629A1 (fr)	1999-03-11
NO20001077D0 (no)	2000-03-02
TR200000602T2 (tr)	2000-12-21
JP2001514254A (ja)	2001-09-11
CO4970738A1 (es)	2000-11-07
ID25620A (id)	2000-10-19
IL134276A0 (en)	2001-04-30
SK1522000A3 (en)	2000-08-14
NZ502660A (en)	2002-02-01
AU9533398A (en)	1999-03-22
PL338954A1 (en)	2000-12-04
HRP980484A2 (en)	1999-06-30
CA2302350A1 (fr)	1999-03-11
BG104222A (en)	2001-02-28
KR20010023615A (ko)	2001-03-26
HUP0004935A3 (en)	2001-12-28
EP1009741A1 (fr)	2000-06-21
TW546295B (en)	2003-08-11

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EP2426125B1 (fr)	2015-12-02	Dérivés de 3 cyano pyridone à disubstitution 1,4 et leurs utilisations en tant que modulateurs allostériques positifs de récepteurs de mGluR2
AU763976B2 (en)	2003-08-07	Th2 differentiation inhibitors
AU711293B2 (en)	1999-10-07	Novel carboxylic acid derivatives, their preparation and use
TW201011040A (en)	2010-03-16	Ring-fused morpholine derivative having pi3k-inhibiting activity
CZ294603B6 (cs)	2005-02-16	Deriváty karboxylové kyseliny
EA010628B1 (ru)	2008-10-30	5-фенилпиримидины, способ их получения, содержащие их средства и их применение
AU748610B2 (en)	2002-06-06	Novel carboxylic acid derivatives, their production and their their use as mixed ETa/ETb endothelin-receptor antagonists
AU740351B2 (en)	2001-11-01	Heterocyclic carboxylic acid derivatives, their preparation ans use as endothelin receptor antagonists
SK176299A3 (en)	2000-06-12	New 'beta'-amino and 'beta'-azidocarboxylic acid derivatives, the production thereof and the use thereof as endothelin receptor antagonists
WO1999042453A1 (fr)	1999-08-26	Derives d'acide pyrimidin-2-yloxy-carboxylique, leur production et leur utilisation comme antagonistes de l'endotheline
AU765345B2 (en)	2003-09-18	Novel carboxylic acid derivatives comprising aryl-substituted nitrogen heterocycles, their production and their use as endothelin receptor antagonists
AU752165B2 (en)	2002-09-05	Novel heterocyclically substituted alpha-hydroxycarboxlic acid derivatives, method for producing the same and their use as endothelin receptor antagonists
CZ326298A3 (cs)	2000-01-12	Deriváty kyseliny karoxylové a jejich použití
MXPA01005635A (en)	2001-12-04	New b-amide and b-sulfonamide carboxylic acid derivatives, their preparation and their use as endothelin receptor antagonists
HUP0201321A2 (hu)	2002-12-28	Új béta-amido- és béta-szulfonamido-karbonsavszármazékok, előállításuk és a vegyületeket tartalmazó gyógyszerkészítmények
AU6561500A (en)	2001-02-05	Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists
SK11752000A3 (sk)	2001-05-10	Nesymetricky substituované deriváty karboxylových kyselín, spôsob ich prípravy a ich použitie ako zmesových antagonistov eta/etb receptora
MXPA00006463A (en)	2001-07-03	5-substituted pyrimidine-2-yloxy carboxylic acid derivatives, the production of the same and their utilization as endothelin antagonists
MXPA00007417A (en)	2001-07-03	Novel unsymmetrically substituted carboxylic acid derivatives, method for producing them, and their use as mixed eta
CA2340167A1 (fr)	2000-02-24	Nouveaux derives de l'acide carbonique porteurs de chaines laterales cetone, leur fabrication et leur utilisation comme antagonistes des recepteurs de l'endotheline
WO2002064573A1 (fr)	2002-08-22	Nouveaux derives d'acide carboxylique contenant des triazines a substitution alkyle, leur production et leur utilisation en tant qu'antagonistes du recepteur d'endotheline

Legal Events

Date	Code	Title	Description
2002-10-03	FGA	Letters patent sealed or granted (standard patent)
2004-03-25	MK14	Patent ceased section 143(a) (annual fees not paid) or expired