HRP980560A2 - New carboxylic acid derivatives, carrying amido side-chains, their production and use as endothelin receptor antagonists - Google Patents

New carboxylic acid derivatives, carrying amido side-chains, their production and use as endothelin receptor antagonists

Info

Publication number: HRP980560A2
Authority: HR; Croatia
Prior art keywords: alkyl; substituted; phenyl; unsubstituted; image
Prior art date: 1997-10-31

Application number

HR19809376.4A

Other languages

English (en)

Croatian (hr)

Inventor

Liliane Unger

Original Assignee

Basf Ag

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.)

1997-10-31

Filing date

1998-10-26

Publication date

1999-08-31

1997-11-28 Priority claimed from DE19752904A external-priority patent/DE19752904A1/de

1998-03-05 Priority claimed from DE1998109376 external-priority patent/DE19809376A1/de

1998-10-26 Application filed by Basf Ag filed Critical Basf Ag

1999-08-31 Publication of HRP980560A2 publication Critical patent/HRP980560A2/hr

Links

229940118365 Endothelin receptor antagonist Drugs 0.000 title claims description 17
239000002308 endothelin receptor antagonist Substances 0.000 title claims description 17
150000001732 carboxylic acid derivatives Chemical class 0.000 title claims description 13
238000004519 manufacturing process Methods 0.000 title claims description 6
125000003368 amide group Chemical group 0.000 title 1
-1 alkali metal cation Chemical class 0.000 claims description 149
229910052736 halogen Inorganic materials 0.000 claims description 76
150000002367 halogens Chemical class 0.000 claims description 76
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 53
150000001875 compounds Chemical class 0.000 claims description 48
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 45
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 42
239000001257 hydrogen Substances 0.000 claims description 37
229910052739 hydrogen Inorganic materials 0.000 claims description 37
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 31
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 28
150000002431 hydrogen Chemical class 0.000 claims description 28
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
229910052757 nitrogen Inorganic materials 0.000 claims description 23
229910052760 oxygen Inorganic materials 0.000 claims description 17
239000001301 oxygen Substances 0.000 claims description 17
229910052717 sulfur Inorganic materials 0.000 claims description 17
125000001624 naphthyl group Chemical group 0.000 claims description 14
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
239000011593 sulfur Chemical group 0.000 claims description 13
102000002045 Endothelin Human genes 0.000 claims description 12
108050009340 Endothelin Proteins 0.000 claims description 12
ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 12
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 11
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 11
239000012634 fragment Substances 0.000 claims description 8
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 8
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
239000013543 active substance Substances 0.000 claims description 6
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
206010020772 Hypertension Diseases 0.000 claims description 5
229910052783 alkali metal Inorganic materials 0.000 claims description 5
239000003112 inhibitor Substances 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 claims description 4
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 4
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
229940079593 drug Drugs 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 4
125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 claims description 4
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
208000002815 pulmonary hypertension Diseases 0.000 claims description 3
230000036454 renin-angiotensin system Effects 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
208000009304 Acute Kidney Injury Diseases 0.000 claims description 2
229940123413 Angiotensin II antagonist Drugs 0.000 claims description 2
201000006474 Brain Ischemia Diseases 0.000 claims description 2
206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
208000033626 Renal failure acute Diseases 0.000 claims description 2
230000001154 acute effect Effects 0.000 claims description 2
201000011040 acute kidney failure Diseases 0.000 claims description 2
208000012998 acute renal failure Diseases 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
239000002333 angiotensin II receptor antagonist Substances 0.000 claims description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
239000002876 beta blocker Substances 0.000 claims description 2
229940097320 beta blocking agent Drugs 0.000 claims description 2
230000015572 biosynthetic process Effects 0.000 claims description 2
206010008118 cerebral infarction Diseases 0.000 claims description 2
208000020832 chronic kidney disease Diseases 0.000 claims description 2
208000022831 chronic renal failure syndrome Diseases 0.000 claims description 2
239000002934 diuretic Substances 0.000 claims description 2
229940030606 diuretics Drugs 0.000 claims description 2
125000001072 heteroaryl group Chemical group 0.000 claims description 2
238000007911 parenteral administration Methods 0.000 claims description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
239000002461 renin inhibitor Substances 0.000 claims description 2
229940086526 renin-inhibitors Drugs 0.000 claims description 2
208000037803 restenosis Diseases 0.000 claims description 2
238000003786 synthesis reaction Methods 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
201000010099 disease Diseases 0.000 claims 4
102100030988 Angiotensin-converting enzyme Human genes 0.000 claims 3
102000003729 Neprilysin Human genes 0.000 claims 2
108090000028 Neprilysin Proteins 0.000 claims 2
229940127291 Calcium channel antagonist Drugs 0.000 claims 1
206010007558 Cardiac failure chronic Diseases 0.000 claims 1
206010060862 Prostate cancer Diseases 0.000 claims 1
208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
239000002981 blocking agent Substances 0.000 claims 1
239000002532 enzyme inhibitor Substances 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
229940124531 pharmaceutical excipient Drugs 0.000 claims 1
239000007858 starting material Substances 0.000 claims 1
150000003254 radicals Chemical class 0.000 description 49
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 42
238000005160 1H NMR spectroscopy Methods 0.000 description 40
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
239000000203 mixture Substances 0.000 description 22
239000002904 solvent Substances 0.000 description 22
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 20
125000004093 cyano group Chemical group *C#N 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
239000012074 organic phase Substances 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 14
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
239000008346 aqueous phase Substances 0.000 description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 12
238000012360 testing method Methods 0.000 description 12
150000005840 aryl radicals Chemical class 0.000 description 11
230000027455 binding Effects 0.000 description 11
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
102000005962 receptors Human genes 0.000 description 11
108020003175 receptors Proteins 0.000 description 11
239000000243 solution Substances 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
102100040611 Endothelin receptor type B Human genes 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
239000002585 base Substances 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
239000000126 substance Substances 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
FONOSWYYBCBQGN-UHFFFAOYSA-N ethylene dione Chemical group O=C=C=O FONOSWYYBCBQGN-UHFFFAOYSA-N 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
125000001424 substituent group Chemical group 0.000 description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
102100033902 Endothelin-1 Human genes 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
238000001816 cooling Methods 0.000 description 5
238000000034 method Methods 0.000 description 5
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 4
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 4
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 description 4
101800004490 Endothelin-1 Proteins 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 4
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 4
150000001408 amides Chemical group 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
239000000872 buffer Substances 0.000 description 4
150000001735 carboxylic acids Chemical class 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
125000003396 thiol group Chemical class [H]S* 0.000 description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
UDDYYKHNWRGBCE-UHFFFAOYSA-N 2-(4,6-dimethylpyrimidin-2-yl)oxy-3,3-diphenyl-3-[2-(phenylmethoxycarbonylamino)ethoxy]propanoic acid Chemical compound CC1=CC(C)=NC(OC(C(O)=O)C(OCCNC(=O)OCC=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 UDDYYKHNWRGBCE-UHFFFAOYSA-N 0.000 description 3
BVCZKXYLBJDZAT-UHFFFAOYSA-N 2-(4,6-dimethylpyrimidin-2-yl)oxy-3-[2-(n-methylanilino)-2-oxoethoxy]-3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1N(C)C(=O)COC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C(C(O)=O)OC1=NC(C)=CC(C)=N1 BVCZKXYLBJDZAT-UHFFFAOYSA-N 0.000 description 3
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
208000001647 Renal Insufficiency Diseases 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000003513 alkali Substances 0.000 description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
201000006370 kidney failure Diseases 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
239000012071 phase Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
125000006850 spacer group Chemical group 0.000 description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
MSQJMBZOUIABKL-UHFFFAOYSA-N 2-(4,6-dimethylpyrimidin-2-yl)oxy-3,3-diphenyl-3-[2-[(2,4,6-trimethylbenzoyl)amino]ethoxy]propanoic acid Chemical compound CC1=CC(C)=CC(C)=C1C(=O)NCCOC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C(C(O)=O)OC1=NC(C)=CC(C)=N1 MSQJMBZOUIABKL-UHFFFAOYSA-N 0.000 description 2
PYYDSKZCKIYMTC-UHFFFAOYSA-N 2-(4,6-dimethylpyrimidin-2-yl)oxy-3-[2-(4-methylanilino)-2-oxoethoxy]-3,3-diphenylpropanoic acid Chemical compound C1=CC(C)=CC=C1NC(=O)COC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C(C(O)=O)OC1=NC(C)=CC(C)=N1 PYYDSKZCKIYMTC-UHFFFAOYSA-N 0.000 description 2
JSRUIZJFRJSVLY-UHFFFAOYSA-N 2-(4,6-dimethylpyrimidin-2-yl)oxy-3-[2-(naphthalene-1-carbonylamino)ethoxy]-3,3-diphenylpropanoic acid Chemical compound CC1=CC(C)=NC(OC(C(O)=O)C(OCCNC(=O)C=2C3=CC=CC=C3C=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 JSRUIZJFRJSVLY-UHFFFAOYSA-N 0.000 description 2
XTIKEKCSSMMOTP-UHFFFAOYSA-N 2-(4,6-dimethylpyrimidin-2-yl)oxy-3-[2-oxo-2-(n-propan-2-ylanilino)ethoxy]-3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1N(C(C)C)C(=O)COC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C(C(O)=O)OC1=NC(C)=CC(C)=N1 XTIKEKCSSMMOTP-UHFFFAOYSA-N 0.000 description 2
PUNLLGCHIIEPNU-HHHXNRCGSA-N 2-[(2s)-2-(4,6-dimethylpyrimidin-2-yl)oxy-3-oxo-1,1-diphenyl-3-phenylmethoxypropoxy]acetic acid Chemical compound CC1=CC(C)=NC(O[C@H](C(=O)OCC=2C=CC=CC=2)C(OCC(O)=O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 PUNLLGCHIIEPNU-HHHXNRCGSA-N 0.000 description 2
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Classifications

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- 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
- C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
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- A—HUMAN NECESSITIES
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- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

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Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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HR19809376.4A 1997-10-31 1998-10-26 New carboxylic acid derivatives, carrying amido side-chains, their production and use as endothelin receptor antagonists HRP980560A2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE19748238		1997-10-31
DE19752904A DE19752904A1 (de)	1997-10-31	1997-11-28	Neue Carbonsäurederivate, die Amidseitenketten tragen, ihre Herstellung und Verwendung als Endothelin-Rezeptorantagonisten
DE1998109376 DE19809376A1 (de)	1998-03-05	1998-03-05	Neue Carbonsäurederivate, die Amidseitenketten tragen, ihre Herstellung und Verwendung als Endothelin-Rezeptorantagonisten

Publications (1)

Publication Number	Publication Date
HRP980560A2 true HRP980560A2 (en)	1999-08-31

Family

ID=27217881

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR19809376.4A HRP980560A2 (en)	1997-10-31	1998-10-26	New carboxylic acid derivatives, carrying amido side-chains, their production and use as endothelin receptor antagonists

Country Status (18)

Country	Link
US (1)	US6509341B1 (de)
EP (1)	EP1027338A2 (de)
JP (1)	JP2001521927A (de)
CN (1)	CN1278251A (de)
AU (1)	AU2266199A (de)
BG (1)	BG104396A (de)
BR (1)	BR9814951A (de)
CA (1)	CA2307770A1 (de)
HR (1)	HRP980560A2 (de)
HU (1)	HUP0100054A3 (de)
ID (1)	ID24278A (de)
IL (1)	IL135347A0 (de)
NO (1)	NO20002124L (de)
NZ (1)	NZ504316A (de)
PL (1)	PL340871A1 (de)
SK (1)	SK4592000A3 (de)
TR (1)	TR200001182T2 (de)
WO (1)	WO1999023078A2 (de)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE19806438A1 (de) *	1998-02-17	1999-08-19	Basf Ag	Neue Carbonsäurederivate mit 5-substituiertem Pyrimidinring, ihre Herstellung und Verwendung
DE19933164A1 (de) *	1999-07-20	2001-01-25	Basf Ag	Neue Carbonsäurederivate mit 5,6 substituiertem Pyrimidinring, ihre Herstellung und Verwendung als Endothelin Rezeptorantagonisten
EP1288202A4 (de)	2000-05-11	2003-07-02	Banyu Pharma Co Ltd	N-acyltetrahydroisochinolin-derivate
DE10025728A1 (de) *	2000-05-25	2001-11-29	Basf Ag	Neue Carbamate und Harnstoffe, ihre Herstellung und Verwendung als Endothelin-Rezeptorantagonisten
WO2002064573A1 (de) *	2001-02-14	2002-08-22	Abbott Gmbh & Co. Kg	Neue carbonsäurederivate mit alkylsubstituierten triazinen, ihre herstellung und verwendung als endothelin-rezeptorantagonisten
DK1243262T3 (da)	2001-03-20	2006-10-02	Sanol Arznei Schwarz Gmbh	Hidtil ukendt anvendelse af en peptidklasse af forbindelser til behandling af ikke-neuropatiske, inflammatoriske smerter
ES2185606T3 (es)	2001-03-21	2003-05-01	Sanol Arznei Schwarz Gmbh	Nuevo uso de una clase de compuestos peptidicos para tratamiento de la alodinia u otros tipos diferentes de dolor cronico o fantasma.
KR20070007931A (ko)	2004-04-16	2007-01-16	쉬바르츠파르마에이지	만성 두통의 예방 및 치료를 위한 펩티드 화합물의 용도
EP1604656A1 (de)	2004-06-09	2005-12-14	Schwarz Pharma Ag	Neue Verwendung von Peptidverbindungen zur Behandlung von amyotropher Lateralsklerose (ALS)
PL1781276T3 (pl)	2004-08-27	2010-11-30	Ucb Pharma Gmbh	Zastosowanie związków peptydowych do leczenia bólu związanego z rakiem kości, bólu indukowanego przez chemioterapię oraz nukleozydy
SG174050A1 (en) *	2006-04-13	2011-09-29	Actelion Pharmaceuticals Ltd	Endothelin receptor antagonists for early stage idiopathic pulmonary fibrosis
WO2007144195A2 (en)	2006-06-15	2007-12-21	Schwarz Pharma Ag	Pharmaceutical composition with synergistic anticonvulsant effect

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE4313413A1 (de) *	1993-04-23	1994-10-27	Basf Ag	3-(Het)aryloxy(thio)-Carbonsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung
DE4313412A1 (de)	1993-04-23	1994-10-27	Basf Ag	3-(Het)aryl-Carbonsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung
DE4411225A1 (de)	1994-03-31	1995-10-05	Basf Ag	Verwendung von Carbonsäurederivaten als Arzneimittel
DE19533023B4 (de) *	1994-10-14	2007-05-16	Basf Ag	Neue Carbonsäurederivate, ihre Herstellung und Verwendung
DE19614534A1 (de)	1996-04-12	1997-10-16	Basf Ag	Neue Carbonsäurederivate, ihre Herstellung und Verwendung

1998
- 1998-10-16 WO PCT/EP1998/006571 patent/WO1999023078A2/de not_active Ceased
- 1998-10-16 CA CA002307770A patent/CA2307770A1/en not_active Abandoned
- 1998-10-16 US US09/529,860 patent/US6509341B1/en not_active Expired - Fee Related
- 1998-10-16 BR BR9814951-2A patent/BR9814951A/pt not_active IP Right Cessation
- 1998-10-16 PL PL98340871A patent/PL340871A1/xx unknown
- 1998-10-16 NZ NZ504316A patent/NZ504316A/xx unknown
- 1998-10-16 JP JP2000518953A patent/JP2001521927A/ja active Pending
- 1998-10-16 CN CN98810875A patent/CN1278251A/zh active Pending
- 1998-10-16 EP EP98966230A patent/EP1027338A2/de not_active Withdrawn
- 1998-10-16 SK SK459-2000A patent/SK4592000A3/sk unknown
- 1998-10-16 HU HU0100054A patent/HUP0100054A3/hu unknown
- 1998-10-16 TR TR2000/01182T patent/TR200001182T2/xx unknown
- 1998-10-16 IL IL13534798A patent/IL135347A0/xx unknown
- 1998-10-16 AU AU22661/99A patent/AU2266199A/en not_active Abandoned
- 1998-10-16 ID IDW20000816A patent/ID24278A/id unknown
- 1998-10-26 HR HR19809376.4A patent/HRP980560A2/hr not_active Application Discontinuation
2000
- 2000-04-26 NO NO20002124A patent/NO20002124L/no not_active Application Discontinuation
- 2000-05-02 BG BG104396A patent/BG104396A/xx unknown

Also Published As

Publication number	Publication date
CA2307770A1 (en)	1999-05-14
IL135347A0 (en)	2001-05-20
US6509341B1 (en)	2003-01-21
TR200001182T2 (tr)	2000-11-21
JP2001521927A (ja)	2001-11-13
WO1999023078A2 (de)	1999-05-14
SK4592000A3 (en)	2000-12-11
EP1027338A2 (de)	2000-08-16
ID24278A (id)	2000-07-13
CN1278251A (zh)	2000-12-27
BG104396A (en)	2001-02-28
NZ504316A (en)	2002-12-20
BR9814951A (pt)	2000-10-03
HUP0100054A1 (hu)	2002-02-28
AU2266199A (en)	1999-05-24
WO1999023078A3 (de)	1999-09-10
NO20002124D0 (no)	2000-04-26
PL340871A1 (en)	2001-03-12
NO20002124L (no)	2000-04-26
HUP0100054A3 (en)	2002-03-28

Legal Events

Date	Code	Title
1999-08-31	A1OB	Publication of a patent application
2000-02-29	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2000-06-30	ARAI	Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application
2008-12-01	OBST	Application withdrawn

Publication	Publication Date	Title
HUP0000664A2 (hu)	2001-04-28	Azinil-oxi- és fenoxi-diaril-karbonsavszármazékok, eljárás előállításukra és alkalmazásuk gyógyszerkészítmények előállítására
HRP980560A2 (en)	1999-08-31	New carboxylic acid derivatives, carrying amido side-chains, their production and use as endothelin receptor antagonists
HRP980331A2 (en)	1999-02-28	New beta-amino and beta-azido carboxylic acid derivatives, the production and the use thereof as endothelin receptor antagonists
JP2001506243A (ja)	2001-05-15	複素環式カルボン酸誘導体、その製造およびエンドセリン受容体拮抗物質としての使用
KR20010023615A (ko)	2001-03-26	신규 카르복실산 유도체, 그 제조 및 혼합 ｅｔａ/ｅｔｂ엔도텔린 수용체 길항제로서의 용도
HRP20000602A2 (en)	2001-06-30	5-substituted pyrimidine-2-yloxy carboxylic acid derivatives, the production of the same and their utilization as endothelin antagonists
HRP980591A2 (en)	1999-08-31	Novel heterocyclically substituted alpha-hydroxycarboxylic acid derivatives, their preparation and use as endothelin receptor antagonists
HRP20000650A2 (en)	2001-06-30	Novel unsymmetrically substituted carboxylic acid derivatives, method for producing them, and their use as mixed et<->a<p>/et<->b<p> receptor antafonists
KR20010101279A (ko)	2001-11-14	신규 β-아미드 및 β-설폰아미드 카르복실산 유도체,그의 제조 방법 및 엔도텔린 수용체 길항제로서의 그의 용도
HRP20010164A2 (en)	2002-04-30	New carboxylic acid derivatives carrying keto side-chains, their production and their use as endothelin-receptor antagonists
CZ20001582A3 (cs)	2000-10-11	Nové deriváty karboxylové kyseliny nesoucí amidový řetězec, způsob přípravy a použití jako antagonistů receptoru endothelínu
KR20020019550A (ko)	2002-03-12	5,6-치환된 피리미딘 고리를 포함하는 신규 카르복실산유도체, 그의 제조 방법 및 엔도텔린 수용체 길항제로서의그의 용도
DE19809376A1 (de)	1999-09-09	Neue Carbonsäurederivate, die Amidseitenketten tragen, ihre Herstellung und Verwendung als Endothelin-Rezeptorantagonisten
CA2375666A1 (en)	2000-12-07	Novel carboxylic acid derivatives comprising aryl-substituted nitrogen heterocycles, their production and their use as endothelin receptor antagonists
HRP970503A2 (en)	1999-06-30	Novel carboxylic acid derivatives, their production and their use as mixed eta/etb receptor antagonists
CZ454399A3 (cs)	2000-04-12	Deriváty kyseliny β-amino a Bacidokarboxylové, způsob její výroby a její použití
KR20010031650A (ko)	2001-04-16	아마이도 측쇄를 가지는 신규한 카르복실산 유도체, 그의제법 및 엔도셀린 수용체 길항제로서의 용도
CZ20003219A3 (cs)	2000-12-13	Nové nesymetricky subtituované deriváty karboxylových kyselin, jejich přípravy a použití jako smíšených antagonistů ETA/ETB receptorů
MXPA00001479A (en)	2001-05-07	Novel carboxylic acid derivatives, their production and their use as mixed eta
CZ61999A3 (cs)	2000-02-16	Deriváty azinyloxy a fenoxy-diarylkarboxylových kyselin, způsob jejich přípravy a použití jako smíšených antagonistů ETA/ETB endotelinových receptorů
CZ2001437A3 (cs)	2001-05-16	Deriváty kyseliny karboxylové a jejich použití