TW546295B - Novel carboxylic acid derivatives, their preparation and use as mixed ETA/ETB receptor antagonists - Google Patents

Novel carboxylic acid derivatives, their preparation and use as mixed ETA/ETB receptor antagonists Download PDF

Info

Publication number: TW546295B
Authority: TW; Taiwan
Prior art keywords: ffi; alkyl; phenyl; group; alkoxy
Prior art date: 1997-09-04

Application number

TW087114595A

Other languages

English (en)

Chinese (zh)

Inventor

Wilhelm Amberg

Rolf Jansen

Dagmar Klinge

Hartmut Riechers

Stefan Hergenroeder

Original Assignee

Abbott Gmbh & Co Kg

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

1998-09-03

Publication date

2003-08-11

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

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

1998-09-03 Application filed by Abbott Gmbh & Co Kg filed Critical Abbott Gmbh & Co Kg

2003-08-11 Application granted granted Critical

2003-08-11 Publication of TW546295B publication Critical patent/TW546295B/zh

Links

150000001732 carboxylic acid derivatives Chemical class 0.000 title claims abstract description 11
102100040611 Endothelin receptor type B Human genes 0.000 title claims description 9
238000002360 preparation method Methods 0.000 title description 5
239000002464 receptor antagonist Substances 0.000 title 1
229940044551 receptor antagonist Drugs 0.000 title 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 30
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
229910052760 oxygen Inorganic materials 0.000 claims abstract description 15
239000001301 oxygen Substances 0.000 claims abstract description 15
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 8
125000001424 substituent group Chemical group 0.000 claims abstract description 8
150000003839 salts Chemical class 0.000 claims abstract description 4
-1 4 -fluorenyl Chemical group 0.000 claims description 72
125000000217 alkyl group Chemical group 0.000 claims description 41
239000003112 inhibitor Substances 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 3
PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
125000003884 phenylalkyl group Chemical group 0.000 claims 1
229940079593 drug Drugs 0.000 abstract description 3
239000003814 drug Substances 0.000 abstract description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
229910052739 hydrogen Inorganic materials 0.000 description 35
150000001875 compounds Chemical class 0.000 description 29
238000011049 filling Methods 0.000 description 29
229910052736 halogen Inorganic materials 0.000 description 21
150000002367 halogens Chemical class 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
229910052717 sulfur Inorganic materials 0.000 description 19
239000011593 sulfur Substances 0.000 description 17
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 15
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
102000002045 Endothelin Human genes 0.000 description 13
108050009340 Endothelin Proteins 0.000 description 13
125000003545 alkoxy group Chemical group 0.000 description 13
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 13
239000000203 mixture Substances 0.000 description 13
238000012360 testing method Methods 0.000 description 13
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 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
239000002904 solvent Substances 0.000 description 12
125000004093 cyano group Chemical group *C#N 0.000 description 11
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 10
239000001257 hydrogen Substances 0.000 description 10
102000005962 receptors Human genes 0.000 description 10
238000000034 method Methods 0.000 description 9
108020003175 receptors Proteins 0.000 description 9
101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 8
210000004027 cell Anatomy 0.000 description 8
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 8
125000004438 haloalkoxy group Chemical group 0.000 description 8
239000000243 solution Substances 0.000 description 8
239000005557 antagonist Substances 0.000 description 7
150000002431 hydrogen Chemical group 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 7
239000000126 substance Substances 0.000 description 7
238000005160 1H NMR spectroscopy Methods 0.000 description 6
101150041968 CDC13 gene Proteins 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
125000001188 haloalkyl group Chemical group 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
229910052784 alkaline earth metal Inorganic materials 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
230000036772 blood pressure Effects 0.000 description 5
230000008018 melting Effects 0.000 description 5
238000002844 melting Methods 0.000 description 5
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 4
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
102100033902 Endothelin-1 Human genes 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
150000001768 cations Chemical class 0.000 description 4
239000010410 layer Substances 0.000 description 4
239000012528 membrane Substances 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Chemical group 0.000 description 4
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
125000004433 nitrogen atom Chemical group N* 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
125000004430 oxygen atom Chemical group O* 0.000 description 4
125000006650 (C2-C4) alkynyl group Chemical group 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
206010020772 Hypertension Diseases 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
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
206010047139 Vasoconstriction Diseases 0.000 description 3
239000002253 acid Substances 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
150000001342 alkaline earth metals Chemical class 0.000 description 3
150000001409 amidines Chemical class 0.000 description 3
208000006673 asthma Diseases 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
230000033228 biological regulation Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
125000001072 heteroaryl group Chemical group 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
239000000463 material Substances 0.000 description 3
NUKZAGXMHTUAFE-UHFFFAOYSA-N methyl hexanoate Chemical compound CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000007921 spray Substances 0.000 description 3
239000003826 tablet Substances 0.000 description 3
125000003396 thiol group Chemical group [H]S* 0.000 description 3
230000025033 vasoconstriction Effects 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
ZOASGOXWEHUTKZ-UHFFFAOYSA-N 1-(Methylthio)-propane Chemical compound CCCSC ZOASGOXWEHUTKZ-UHFFFAOYSA-N 0.000 description 2
PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 description 2
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
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-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
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
FEMMJJHSNYGVAI-UHFFFAOYSA-N 6-(3,4-dimethoxyphenyl)hexanoic acid Chemical compound COC1=CC=C(CCCCCC(O)=O)C=C1OC FEMMJJHSNYGVAI-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
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KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
ZERULLAPCVRMCO-UHFFFAOYSA-N Dipropyl sulfide Chemical compound CCCSCCC ZERULLAPCVRMCO-UHFFFAOYSA-N 0.000 description 2
229940118365 Endothelin receptor antagonist Drugs 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
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UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
150000001335 aliphatic alkanes Chemical class 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 2
208000011775 arteriosclerosis disease Diseases 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
239000011425 bamboo Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
210000001715 carotid artery Anatomy 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
125000000392 cycloalkenyl group Chemical group 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
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239000002308 endothelin receptor antagonist Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
SHZIWNPUGXLXDT-UHFFFAOYSA-N ethyl hexanoate Chemical compound CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 description 2
125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 2
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QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
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125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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238000003786 synthesis reaction Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
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125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
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125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
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125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
DZJCKEJIFNQWSP-UHFFFAOYSA-N 2-(4-methoxy-6-methylpyrimidin-2-yl)oxy-3,6-diphenyl-3-[2-(3,4,5-trimethoxyphenyl)ethoxy]hexanoic acid Chemical class COC1=CC(C)=NC(OC(C(O)=O)C(CCCC=2C=CC=CC=2)(OCCC=2C=C(OC)C(OC)=C(OC)C=2)C=2C=CC=CC=2)=N1 DZJCKEJIFNQWSP-UHFFFAOYSA-N 0.000 description 1
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125000004791 2-fluoroethoxy group Chemical group FCCO* 0.000 description 1
MJXSDNAEQWGZGP-UHFFFAOYSA-N 2-hydroxy-3-methoxy-3,6-diphenylhexanoic acid Chemical compound C=1C=CC=CC=1C(OC)(C(O)C(O)=O)CCCC1=CC=CC=C1 MJXSDNAEQWGZGP-UHFFFAOYSA-N 0.000 description 1
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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
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- A—HUMAN NECESSITIES
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- 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
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- 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
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- 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
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- 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
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- 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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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)
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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)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (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)

TW087114595A 1997-09-04 1998-09-03 Novel carboxylic acid derivatives, their preparation and use as mixed ETA/ETB receptor antagonists TW546295B (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
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

Publications (1)

Publication Number	Publication Date
TW546295B true TW546295B (en)	2003-08-11

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ID=26039663

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Application Number	Title	Priority Date	Filing Date
TW087114595A TW546295B (en)	1997-09-04	1998-09-03	Novel carboxylic acid derivatives, their preparation and use as mixed ETA/ETB receptor antagonists

Country Status (21)

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

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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
KR20090020559A (ko) *	2006-05-29	2009-02-26	니콕스 에스. 에이.	엔도셀린 수용체 길항제로서의 질화 헤테로시클릭 화합물
BRPI0909105A2 (pt)	2008-03-05	2015-08-25	Boehringer Ingelheim Int	Derivados de piridina tricíclicos, composição farmacêutica e uso dos mesmos, bem como processos para preparar os ditos compostos e a dita composição farmacêutica
ES2462065T3 (es) *	2009-07-10	2014-05-22	Cadila Healthcare Limited	Proceso mejorado para la preparación de Ambrisentán e intermedios novedosos de este
UY33229A (es)	2010-02-19	2011-09-30	Boehringer Ingelheim Int	Derivados de piridina tricíclicos, medicamentos que contienen tales compuestos, su uso y proceso pa ra su preparación
EP2760868B1 (en)	2011-08-17	2018-04-25	Boehringer Ingelheim International GmbH	Furo[3,4-c]quinoline derivatives, medicaments containing such compounds, their use and process for their preparation

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DE4411225A1 (de) *	1994-03-31	1995-10-05	Basf Ag	Verwendung von Carbonsäurederivaten als Arzneimittel
DE19533023B4 (de) *	1994-10-14	2007-05-16	Basf Ag	Neue Carbonsäurederivate, ihre Herstellung und Verwendung
JP2000504013A (ja) *	1996-02-01	2000-04-04	スミスクライン・ビーチャム・コーポレイション	エンドセリンレセプターアンタゴニスト
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 KR KR1020007002264A patent/KR20010023615A/ko not_active Withdrawn
- 1998-08-24 ID IDW20000386D patent/ID25620A/id unknown
- 1998-08-24 JP JP2000508669A patent/JP2001514254A/ja active Pending
- 1998-08-24 PL PL98338954A patent/PL338954A1/xx unknown
- 1998-08-24 AU AU95333/98A patent/AU748610B2/en not_active Ceased
- 1998-08-24 CA CA002302350A patent/CA2302350A1/en not_active Abandoned
- 1998-08-24 WO PCT/EP1998/005354 patent/WO1999011629A1/de not_active Ceased
- 1998-08-24 SK SK152-2000A patent/SK1522000A3/sk unknown
- 1998-08-24 BR BR9811631-2A patent/BR9811631A/pt not_active IP Right Cessation
- 1998-08-24 NZ NZ502660A patent/NZ502660A/en unknown
- 1998-08-24 CN CN98808862A patent/CN1269792A/zh active Pending
- 1998-08-24 IL IL13427698A patent/IL134276A0/xx unknown
- 1998-08-24 EP EP98948859A patent/EP1009741A1/de not_active Withdrawn
- 1998-08-24 HU HU0004935A patent/HUP0004935A3/hu unknown
- 1998-08-24 TR TR2000/00602T patent/TR200000602T2/xx unknown
- 1998-09-02 HR HR19811915.1A patent/HRP980484A2/hr not_active Application Discontinuation
- 1998-09-03 TW TW087114595A patent/TW546295B/zh active
- 1998-09-03 AR ARP980104402A patent/AR017052A1/es not_active Application Discontinuation
- 1998-09-03 CO CO98050561A patent/CO4970738A1/es unknown
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
HUP0004935A3 (en)	2001-12-28
WO1999011629A1 (de)	1999-03-11
EP1009741A1 (de)	2000-06-21
BG104222A (en)	2001-02-28
SK1522000A3 (en)	2000-08-14
JP2001514254A (ja)	2001-09-11
AU748610B2 (en)	2002-06-06
PL338954A1 (en)	2000-12-04
CO4970738A1 (es)	2000-11-07
KR20010023615A (ko)	2001-03-26
NZ502660A (en)	2002-02-01
HUP0004935A2 (hu)	2001-10-28
NO20001077L (no)	2000-03-02
AU9533398A (en)	1999-03-22
BR9811631A (pt)	2000-09-26
CN1269792A (zh)	2000-10-11
IL134276A0 (en)	2001-04-30
ID25620A (id)	2000-10-19
AR017052A1 (es)	2001-08-22
CA2302350A1 (en)	1999-03-11
NO20001077D0 (no)	2000-03-02
TR200000602T2 (tr)	2000-12-21
HRP980484A2 (en)	1999-06-30

Publication	Publication Date	Title
NO310497B1 (no)	2001-07-16	Pyrimidin- eller triazin-karboksylsyrederivater, hvilke kan anvendes som legemidler
SK134498A3 (en)	1999-03-12	Novel 'alpha'-hydroxylic acid derivatives, their production and use
TW546295B (en)	2003-08-11	Novel carboxylic acid derivatives, their preparation and use as mixed ETA/ETB receptor antagonists
NO311802B1 (no)	2002-01-28	Nye karboksylsyre-derivater og deres anvendelse
HRP980560A2 (en)	1999-08-31	New carboxylic acid derivatives, carrying amido side-chains, their production and use as endothelin receptor antagonists
CA2294050A1 (en)	1998-12-30	New .beta.-amino and .beta.-azidocarboxylic acid derivatives, the production thereof and the use thereof as endothelin receptor antagonists
TW579376B (en)	2004-03-11	Novel carboxylic acid derivatives having a 5-substituted pyrimidine ring, their preparation and use
HRP980591A2 (en)	1999-08-31	Novel heterocyclically substituted alpha-hydroxycarboxylic acid derivatives, their preparation and use 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
AU765345B2 (en)	2003-09-18	Novel carboxylic acid derivatives comprising aryl-substituted nitrogen heterocycles, their production 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
MXPA00007417A (en)	2001-07-03	Novel unsymmetrically substituted carboxylic acid derivatives, method for producing them, and their use as mixed eta
CA2340167A1 (en)	2000-02-24	New carboxylic acid derivatives carrying keto side-chains, their production and their use as endothelin-receptor antagonists
CZ2000743A3 (cs)	2000-06-14	Deriváty kyseliny karboxylové a jejich použití
MXPA00006463A (en)	2001-07-03	5-substituted pyrimidine-2-yloxy carboxylic acid derivatives, the production of the same and their utilization as endothelin antagonists
CZ2001437A3 (cs)	2001-05-16	Deriváty kyseliny karboxylové a jejich použití
CZ20002963A3 (cs)	2000-11-15	Nové deriváty karboxylové kyseliny, obsahující 5- substituovaný pyrimidinový kruh, jejich příprava a použiti
HRP970503A2 (en)	1999-06-30	Novel carboxylic acid derivatives, their production and their use as mixed eta/etb receptor antagonists
CZ20003219A3 (cs)	2000-12-13	Nové nesymetricky subtituované deriváty karboxylových kyselin, jejich přípravy a použití jako smíšených antagonistů ETA/ETB receptorů
CZ20001582A3 (cs)	2000-10-11	Nové deriváty karboxylové kyseliny nesoucí amidový řetězec, způsob přípravy a použití jako antagonistů receptoru endothelínu
CZ454399A3 (cs)	2000-04-12	Deriváty kyseliny β-amino a Bacidokarboxylové, způsob její výroby a její použití
MXPA99001995A (en)		New derivatives of oxilic acid, its obtaining and use in quality of mixed antagonists of receivers eta /
MXPA00001479A (en)	2001-05-07	Novel carboxylic acid derivatives, their production and their use as mixed eta