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 antagonistsInfo
- Publication number
- HRP980560A2 HRP980560A2 HR19809376.4A HRP980560A HRP980560A2 HR P980560 A2 HRP980560 A2 HR P980560A2 HR P980560 A HRP980560 A HR P980560A HR P980560 A2 HRP980560 A2 HR P980560A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- substituted
- phenyl
- unsubstituted
- image
- Prior art date
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
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- 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
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
- C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—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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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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) | NO20002124D0 (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)
| 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 |
| CA2408343A1 (en) | 2000-05-11 | 2002-11-07 | Banyu Pharmaceutical Co., Ltd. | N-acyltetrahydroisoquinoline derivatives |
| 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 |
| ATE327744T1 (de) | 2001-03-20 | 2006-06-15 | Sanol Arznei Schwarz Gmbh | Neue verwendung von peptidverbindungen bei der behandlung von nicht-neuropathischem entzündungsschmerz |
| DE60100055T2 (de) | 2001-03-21 | 2003-07-24 | Schwarz Pharma Ag | Neue Verwendung einer Klasse von Peptidverbindungen zur Behandlung von Allodynie oder andere Arten von chronischen oder Phantomschmerzen |
| 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 |
| JP2009533420A (ja) * | 2006-04-13 | 2009-09-17 | アクテリオン ファーマシューティカルズ リミテッド | 早期特発性肺線維症の治療 |
| KR20150003925A (ko) | 2006-06-15 | 2015-01-09 | 유씨비 파르마 게엠베하 | 상승적 항경련 효과를 갖는 약제학적 조성물 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4313412A1 (de) | 1993-04-23 | 1994-10-27 | Basf Ag | 3-(Het)aryl-Carbonsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung |
| DE4313413A1 (de) * | 1993-04-23 | 1994-10-27 | Basf Ag | 3-(Het)aryloxy(thio)-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 AU AU22661/99A patent/AU2266199A/en not_active Abandoned
- 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 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 HU HU0100054A patent/HUP0100054A3/hu unknown
- 1998-10-16 ID IDW20000816A patent/ID24278A/id unknown
- 1998-10-16 IL IL13534798A patent/IL135347A0/xx unknown
- 1998-10-16 PL PL98340871A patent/PL340871A1/xx unknown
- 1998-10-16 SK SK459-2000A patent/SK4592000A3/sk unknown
- 1998-10-16 BR BR9814951-2A patent/BR9814951A/pt not_active IP Right Cessation
- 1998-10-16 WO PCT/EP1998/006571 patent/WO1999023078A2/de not_active Application Discontinuation
- 1998-10-16 EP EP98966230A patent/EP1027338A2/de not_active Withdrawn
- 1998-10-16 TR TR2000/01182T patent/TR200001182T2/xx unknown
- 1998-10-26 HR HR19809376.4A patent/HRP980560A2/hr not_active Application Discontinuation
-
2000
- 2000-04-26 NO NO20002124A patent/NO20002124D0/no not_active Application Discontinuation
- 2000-05-02 BG BG104396A patent/BG104396A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001521927A (ja) | 2001-11-13 |
| HUP0100054A3 (en) | 2002-03-28 |
| NO20002124L (no) | 2000-04-26 |
| AU2266199A (en) | 1999-05-24 |
| CN1278251A (zh) | 2000-12-27 |
| ID24278A (id) | 2000-07-13 |
| HUP0100054A1 (hu) | 2002-02-28 |
| SK4592000A3 (en) | 2000-12-11 |
| CA2307770A1 (en) | 1999-05-14 |
| BR9814951A (pt) | 2000-10-03 |
| WO1999023078A2 (de) | 1999-05-14 |
| TR200001182T2 (tr) | 2000-11-21 |
| WO1999023078A3 (de) | 1999-09-10 |
| BG104396A (en) | 2001-02-28 |
| US6509341B1 (en) | 2003-01-21 |
| NZ504316A (en) | 2002-12-20 |
| EP1027338A2 (de) | 2000-08-16 |
| IL135347A0 (en) | 2001-05-20 |
| NO20002124D0 (no) | 2000-04-26 |
| PL340871A1 (en) | 2001-03-12 |
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