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
206010003210 Arteriosclerosis Diseases 0.000 description 2
235000017166 Bambusa arundinacea Nutrition 0.000 description 2
235000017491 Bambusa tulda Nutrition 0.000 description 2
241001330002 Bambuseae Species 0.000 description 2
241001674044 Blattodea Species 0.000 description 2
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
235000015334 Phyllostachys viridis Nutrition 0.000 description 2
241000700159 Rattus Species 0.000 description 2
208000001647 Renal Insufficiency Diseases 0.000 description 2
229910000831 Steel Inorganic materials 0.000 description 2
208000006011 Stroke Diseases 0.000 description 2
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
230000000694 effects Effects 0.000 description 2
230000003511 endothelial effect Effects 0.000 description 2
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
238000009472 formulation Methods 0.000 description 2
150000002440 hydroxy compounds Chemical class 0.000 description 2
239000005457 ice water Substances 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
208000001286 intracranial vasospasm Diseases 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
210000004731 jugular vein Anatomy 0.000 description 2
201000006370 kidney failure Diseases 0.000 description 2
239000003446 ligand Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
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
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
UAJUXJSXCLUTNU-UHFFFAOYSA-N pranlukast Chemical compound C=1C=C(OCCCCC=2C=CC=CC=2)C=CC=1C(=O)NC(C=1)=CC=C(C(C=2)=O)C=1OC=2C=1N=NNN=1 UAJUXJSXCLUTNU-UHFFFAOYSA-N 0.000 description 2
229960004583 pranlukast Drugs 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
208000002815 pulmonary hypertension Diseases 0.000 description 2
238000000746 purification Methods 0.000 description 2
230000036454 renin-angiotensin system Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
239000010959 steel Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
125000004434 sulfur atom Chemical group 0.000 description 2
RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
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
230000002792 vascular Effects 0.000 description 2
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
OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 1
CRUILBNAQILVHZ-UHFFFAOYSA-N 1,2,3-trimethoxybenzene Chemical group COC1=CC=CC(OC)=C1OC CRUILBNAQILVHZ-UHFFFAOYSA-N 0.000 description 1
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
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
125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
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
PGIOANNVJQQCDT-UHFFFAOYSA-N 2-phenylhexanoic acid Chemical compound CCCCC(C(O)=O)C1=CC=CC=C1 PGIOANNVJQQCDT-UHFFFAOYSA-N 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
LNMBCRKRCIMQLW-UHFFFAOYSA-N 2-tert-butylsulfanyl-2-methylpropane Chemical compound CC(C)(C)SC(C)(C)C LNMBCRKRCIMQLW-UHFFFAOYSA-N 0.000 description 1
ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 1
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
QSNKQHXTPVICBY-UHFFFAOYSA-N 3-methoxy-2-(4-methoxy-6-methylpyrimidin-2-yl)oxy-3,6-diphenylhexanoic acid Chemical compound COC1=CC(C)=NC(OC(C(O)=O)C(CCCC=2C=CC=CC=2)(OC)C=2C=CC=CC=2)=N1 QSNKQHXTPVICBY-UHFFFAOYSA-N 0.000 description 1
CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
UQRONKZLYKUEMO-UHFFFAOYSA-N 4-methyl-1-(2,4,6-trimethylphenyl)pent-4-en-2-one Chemical group CC(=C)CC(=O)Cc1c(C)cc(C)cc1C UQRONKZLYKUEMO-UHFFFAOYSA-N 0.000 description 1
208000009304 Acute Kidney Injury Diseases 0.000 description 1
108010064733 Angiotensins Proteins 0.000 description 1
102000015427 Angiotensins Human genes 0.000 description 1
BHELIUBJHYAEDK-OAIUPTLZSA-N Aspoxicillin Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3[C@H](C(C)(C)S[C@@H]32)C(O)=O)=O)NC(=O)[C@H](N)CC(=O)NC)=CC=C(O)C=C1 BHELIUBJHYAEDK-OAIUPTLZSA-N 0.000 description 1
108010001478 Bacitracin Proteins 0.000 description 1
206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
206010005746 Blood pressure fluctuation Diseases 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
201000006474 Brain Ischemia Diseases 0.000 description 1
SNTAILVTQOUCCY-UHFFFAOYSA-N CC1=CC=NC(N1C)C Chemical compound CC1=CC=NC(N1C)C SNTAILVTQOUCCY-UHFFFAOYSA-N 0.000 description 1
101100172118 Caenorhabditis elegans eif-2Bgamma gene Proteins 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
229920000742 Cotton Polymers 0.000 description 1
HTIRHQRTDBPHNZ-UHFFFAOYSA-N Dibutyl sulfide Chemical compound CCCCSCCCC HTIRHQRTDBPHNZ-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 1
102000010180 Endothelin receptor Human genes 0.000 description 1
108050001739 Endothelin receptor Proteins 0.000 description 1
101800004490 Endothelin-1 Proteins 0.000 description 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
206010061459 Gastrointestinal ulcer Diseases 0.000 description 1
206010018341 Gliosis Diseases 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
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 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
241001306288 Ophrys fuciflora Species 0.000 description 1
206010053159 Organ failure Diseases 0.000 description 1
206010033645 Pancreatitis Diseases 0.000 description 1
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical group C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical group CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
208000003782 Raynaud disease Diseases 0.000 description 1
208000012322 Raynaud phenomenon Diseases 0.000 description 1
208000033626 Renal failure acute Diseases 0.000 description 1
101100017604 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HOR7 gene Proteins 0.000 description 1
206010040070 Septic Shock Diseases 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
241000187747 Streptomyces Species 0.000 description 1
208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
229910052776 Thorium Inorganic materials 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
102000004142 Trypsin Human genes 0.000 description 1
108090000631 Trypsin Proteins 0.000 description 1
JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
201000011040 acute kidney failure Diseases 0.000 description 1
206010000891 acute myocardial infarction Diseases 0.000 description 1
208000012998 acute renal failure Diseases 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
239000003513 alkali Substances 0.000 description 1
125000004450 alkenylene group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000004448 alkyl carbonyl group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical group 0.000 description 1
125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
125000005336 allyloxy group Chemical group 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
230000002225 anti-radical effect Effects 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
229960003071 bacitracin Drugs 0.000 description 1
229930184125 bacitracin Natural products 0.000 description 1
CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
235000021028 berry Nutrition 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
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 1
229910052797 bismuth Inorganic materials 0.000 description 1
JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
239000007767 bonding agent Substances 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
150000001722 carbon compounds Chemical class 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
210000004413 cardiac myocyte Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 description 1
208000020832 chronic kidney disease Diseases 0.000 description 1
208000022831 chronic renal failure syndrome Diseases 0.000 description 1
230000015271 coagulation Effects 0.000 description 1
238000005345 coagulation Methods 0.000 description 1
239000013066 combination product Substances 0.000 description 1
229940127555 combination product Drugs 0.000 description 1
239000002872 contrast media Substances 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
125000003963 dichloro group Chemical group Cl* 0.000 description 1
125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 description 1
LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical compound CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 description 1
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
230000029087 digestion Effects 0.000 description 1
125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
210000003038 endothelium Anatomy 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
230000007387 gliosis Effects 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000012010 growth Effects 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000012771 household material Substances 0.000 description 1
239000003906 humectant Substances 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
ROPLCSFPUPWHGJ-UHFFFAOYSA-N hydroxycyanamide Chemical compound ONC#N ROPLCSFPUPWHGJ-UHFFFAOYSA-N 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical class O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
QSPAEUKIWTXLSC-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li+].CC(C)NC(C)C QSPAEUKIWTXLSC-UHFFFAOYSA-N 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
201000008806 mesenchymal cell neoplasm Diseases 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
YGXHKTRPOQOKRC-UHFFFAOYSA-N methyl 6-phenylhexanoate Chemical compound COC(=O)CCCCCC1=CC=CC=C1 YGXHKTRPOQOKRC-UHFFFAOYSA-N 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000001989 nasopharynx Anatomy 0.000 description 1
210000000885 nephron Anatomy 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000002902 organometallic compounds Chemical class 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
239000005022 packaging material Substances 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
BYTCDABWEGFPLT-UHFFFAOYSA-L potassium;sodium;dihydroxide Chemical compound [OH-].[OH-].[Na+].[K+] BYTCDABWEGFPLT-UHFFFAOYSA-L 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000000047 product Substances 0.000 description 1
239000001294 propane Substances 0.000 description 1
239000003380 propellant Substances 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
238000012552 review Methods 0.000 description 1
229910052702 rhenium Inorganic materials 0.000 description 1
WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000004575 stone Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium group Chemical group [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
125000004354 sulfur functional group Chemical group 0.000 description 1
239000000725 suspension Substances 0.000 description 1
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
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
238000002604 ultrasonography Methods 0.000 description 1
210000001186 vagus nerve Anatomy 0.000 description 1
238000007631 vascular surgery Methods 0.000 description 1
230000006442 vascular tone Effects 0.000 description 1
238000009423 ventilation Methods 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 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
- C07D239/52—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

Landscapes

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

Family

ID=26039663

Family Applications (1)

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)

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
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
US20090263472A1 (en) *	2006-05-29	2009-10-22	Nicox S.A.	Endothelin receptor antagonist derivatives
WO2009109549A1 (fr)	2008-03-05	2009-09-11	Boehringer Ingelheim International Gmbh	Dérivés de pyridines tricycliques, médicaments contenant ces composés, leur utilisation et leur procédé de préparation
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
CA2790643A1 (fr)	2010-02-19	2011-08-25	Boehringer Ingelheim International Gmbh	Derives tricycliques de pyridine, medicaments contenant lesdits composes, utilisation associee et procede de preparation associee
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

Family Cites Families (5)

* 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
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 CA CA002302350A patent/CA2302350A1/fr not_active Abandoned
- 1998-08-24 JP JP2000508669A patent/JP2001514254A/ja active Pending
- 1998-08-24 TR TR2000/00602T patent/TR200000602T2/xx unknown
- 1998-08-24 HU HU0004935A patent/HUP0004935A3/hu unknown
- 1998-08-24 CN CN98808862A patent/CN1269792A/zh active Pending
- 1998-08-24 ID IDW20000386D patent/ID25620A/id unknown
- 1998-08-24 IL IL13427698A patent/IL134276A0/xx unknown
- 1998-08-24 NZ NZ502660A patent/NZ502660A/en unknown
- 1998-08-24 EP EP98948859A patent/EP1009741A1/fr not_active Withdrawn
- 1998-08-24 WO PCT/EP1998/005354 patent/WO1999011629A1/fr not_active Ceased
- 1998-08-24 AU AU95333/98A patent/AU748610B2/en not_active Ceased
- 1998-08-24 KR KR1020007002264A patent/KR20010023615A/ko not_active Withdrawn
- 1998-08-24 BR BR9811631-2A patent/BR9811631A/pt not_active IP Right Cessation
- 1998-08-24 PL PL98338954A patent/PL338954A1/xx unknown
- 1998-08-24 SK SK152-2000A patent/SK1522000A3/sk unknown
- 1998-09-02 HR HR19811915.1A patent/HRP980484A2/hr not_active Application Discontinuation
- 1998-09-03 AR ARP980104402A patent/AR017052A1/es not_active Application Discontinuation
- 1998-09-03 CO CO98050561A patent/CO4970738A1/es unknown
- 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
HUP0004935A3 (en)	2001-12-28
JP2001514254A (ja)	2001-09-11
BR9811631A (pt)	2000-09-26
CO4970738A1 (es)	2000-11-07
KR20010023615A (ko)	2001-03-26
SK1522000A3 (en)	2000-08-14
AU9533398A (en)	1999-03-22
PL338954A1 (en)	2000-12-04
ID25620A (id)	2000-10-19
HRP980484A2 (en)	1999-06-30
NZ502660A (en)	2002-02-01
NO20001077L (no)	2000-03-02
CN1269792A (zh)	2000-10-11
IL134276A0 (en)	2001-04-30
HUP0004935A2 (hu)	2001-10-28
TR200000602T2 (tr)	2000-12-21
CA2302350A1 (fr)	1999-03-11
BG104222A (en)	2001-02-28
NO20001077D0 (no)	2000-03-02
WO1999011629A1 (fr)	1999-03-11
AR017052A1 (es)	2001-08-22
EP1009741A1 (fr)	2000-06-21
AU748610B2 (en)	2002-06-06

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
TW426672B (en)	2001-03-21	Novel carboxylic acid derivatives, their preparation 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 (fr)	1998-12-30	Nouveaux derives d'acide .beta.-amino et .beta.-azido carboxylique, leur preparation et leur utilisation comme antagonistes du recepteur de l'endotheline
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 (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
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