SK11512000A3 - 5-substituované deriváty pyrimidín-2-yloxy karboxylových kyselín, ich príprava a ich využitie ako antagonistov endotelínu - Google Patents

5-substituované deriváty pyrimidín-2-yloxy karboxylových kyselín, ich príprava a ich využitie ako antagonistov endotelínu Download PDF

Info

Publication number: SK11512000A3
Authority: SK; Slovakia
Prior art keywords: alkyl; group; phenyl; alkoxy; halogen
Prior art date: 1998-02-17

Application number

SK1151-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Wilhelm Amberg

Rolf Jansen

Andreas Kling

Dagmar Klinge

Hartmut Riechers

Stefan Hergenr�Der

Manfred Raschack

Liliane Unger

Original Assignee

Basf Aktiengesellschaft

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.)

1998-02-17

Filing date

1999-02-05

Publication date

2001-04-09

1999-02-05 Application filed by Basf Aktiengesellschaft filed Critical Basf Aktiengesellschaft

2001-04-09 Publication of SK11512000A3 publication Critical patent/SK11512000A3/sk

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-1 5-substituted pyrimidine-2-yloxy carboxylic acid Chemical class 0.000 title claims abstract description 99
102000002045 Endothelin Human genes 0.000 title claims abstract description 23
108050009340 Endothelin Proteins 0.000 title claims abstract description 23
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 title claims abstract description 23
239000005557 antagonist Substances 0.000 title claims abstract description 10
150000001875 compounds Chemical class 0.000 claims abstract description 42
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 41
229910052736 halogen Inorganic materials 0.000 claims abstract description 37
150000002367 halogens Chemical class 0.000 claims abstract description 32
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 26
125000005843 halogen group Chemical group 0.000 claims abstract description 24
229910052717 sulfur Inorganic materials 0.000 claims abstract description 18
150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 14
125000001424 substituent group Chemical group 0.000 claims abstract description 14
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 13
239000001257 hydrogen Substances 0.000 claims abstract description 13
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
125000001624 naphthyl group Chemical group 0.000 claims abstract description 13
239000011593 sulfur Substances 0.000 claims abstract description 13
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 10
229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
239000001301 oxygen Substances 0.000 claims abstract description 10
150000002431 hydrogen Chemical class 0.000 claims abstract description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 7
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 7
201000010099 disease Diseases 0.000 claims abstract description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 7
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 6
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims abstract description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims abstract description 5
125000004434 sulfur atom Chemical group 0.000 claims abstract description 5
150000003839 salts Chemical class 0.000 claims abstract description 4
125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 3
125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 3
125000001072 heteroaryl group Chemical group 0.000 claims abstract 4
125000002883 imidazolyl group Chemical group 0.000 claims abstract 2
125000000217 alkyl group Chemical group 0.000 claims description 21
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 17
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
125000004093 cyano group Chemical group *C#N 0.000 claims description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 12
239000002308 endothelin receptor antagonist Substances 0.000 claims description 9
229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 8
239000003112 inhibitor Substances 0.000 claims description 7
125000004430 oxygen atom Chemical group O* 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 6
125000006650 (C2-C4) alkynyl group Chemical group 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 5
206010020772 Hypertension Diseases 0.000 claims description 5
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims description 5
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims description 5
229910052783 alkali metal Inorganic materials 0.000 claims description 5
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 4
FONOSWYYBCBQGN-UHFFFAOYSA-N ethylene dione Chemical group O=C=C=O FONOSWYYBCBQGN-UHFFFAOYSA-N 0.000 claims description 4
206010019280 Heart failures 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
229910052799 carbon Inorganic materials 0.000 claims description 3
208000002815 pulmonary hypertension Diseases 0.000 claims description 3
230000036454 renin-angiotensin system Effects 0.000 claims description 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
208000009304 Acute Kidney Injury Diseases 0.000 claims description 2
206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 2
201000006474 Brain Ischemia Diseases 0.000 claims description 2
206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
208000004403 Prostatic Hyperplasia 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
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
239000002876 beta blocker Substances 0.000 claims description 2
229940097320 beta blocking agent Drugs 0.000 claims description 2
206010008118 cerebral infarction Diseases 0.000 claims description 2
230000001684 chronic effect Effects 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
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
102000003729 Neprilysin Human genes 0.000 claims 2
108090000028 Neprilysin Proteins 0.000 claims 2
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 2
229940127291 Calcium channel antagonist Drugs 0.000 claims 1
206010060862 Prostate cancer Diseases 0.000 claims 1
208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims 1
239000002981 blocking agent Substances 0.000 claims 1
125000000753 cycloalkyl group Chemical group 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
229940124531 pharmaceutical excipient Drugs 0.000 claims 1
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
125000003831 tetrazolyl group Chemical group 0.000 claims 1
125000001425 triazolyl group Chemical group 0.000 claims 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract description 3
150000003536 tetrazoles Chemical class 0.000 abstract description 3
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 abstract 1
150000003254 radicals Chemical class 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
102000005962 receptors Human genes 0.000 description 12
108020003175 receptors Proteins 0.000 description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
239000002585 base Substances 0.000 description 10
239000000203 mixture Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
238000012360 testing method Methods 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 8
241001465754 Metazoa Species 0.000 description 7
230000027455 binding Effects 0.000 description 7
230000000694 effects Effects 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
210000004027 cell Anatomy 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
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 5
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 4
102100033902 Endothelin-1 Human genes 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
125000004414 alkyl thio group Chemical group 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical group FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 4
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
239000000243 solution Substances 0.000 description 4
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
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
150000001735 carboxylic acids Chemical class 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
239000012528 membrane Substances 0.000 description 3
238000000034 method Methods 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000012071 phase Substances 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical group [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
102000010180 Endothelin receptor Human genes 0.000 description 2
108050001739 Endothelin receptor Proteins 0.000 description 2
101800004490 Endothelin-1 Proteins 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
102000001708 Protein Isoforms Human genes 0.000 description 2
108010029485 Protein Isoforms Proteins 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
208000001647 Renal Insufficiency Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
208000006011 Stroke Diseases 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
206010047139 Vasoconstriction Diseases 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
150000005840 aryl radicals Chemical class 0.000 description 2
AXFHDDDNZLFQKF-UHFFFAOYSA-N benzyl 2-(5-fluoro-4-morpholin-4-ylpyrimidin-2-yl)oxy-3-methoxy-3,3-diphenylpropanoate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OC)C(C(=O)OCC=1C=CC=CC=1)OC(N=1)=NC=C(F)C=1N1CCOCC1 AXFHDDDNZLFQKF-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
210000004204 blood vessel Anatomy 0.000 description 2
230000037396 body weight Effects 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
150000003857 carboxamides Chemical class 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
229910052801 chlorine Inorganic materials 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
238000010586 diagram Methods 0.000 description 2
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125000001188 haloalkyl group Chemical group 0.000 description 2
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ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
239000002609 medium Substances 0.000 description 2
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125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
230000002085 persistent effect Effects 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
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239000002243 precursor Substances 0.000 description 2
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239000000126 substance Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
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VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
125000000335 thiazolyl group Chemical group 0.000 description 2
125000003396 thiol group Chemical class [H]S* 0.000 description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
230000025033 vasoconstriction Effects 0.000 description 2
238000005303 weighing Methods 0.000 description 2
125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
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
125000004711 1,1-dimethylethylthio group Chemical group CC(C)(S*)C 0.000 description 1
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
VZAWCLCJGSBATP-UHFFFAOYSA-N 1-cycloundecyl-1,2-diazacycloundecane Chemical compound C1CCCCCCCCCC1N1NCCCCCCCCC1 VZAWCLCJGSBATP-UHFFFAOYSA-N 0.000 description 1
125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 description 1
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- 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
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- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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SK1151-2000A 1998-02-17 1999-02-05 5-substituované deriváty pyrimidín-2-yloxy karboxylových kyselín, ich príprava a ich využitie ako antagonistov endotelínu SK11512000A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19806438A DE19806438A1 (de)	1998-02-17	1998-02-17	Neue Carbonsäurederivate mit 5-substituiertem Pyrimidinring, ihre Herstellung und Verwendung
PCT/EP1999/000776 WO1999042453A1 (de)	1998-02-17	1999-02-05	5-substituierte pyrimidin-2-yloxy-carbonsäurederivate, deren herstellung und deren verwendung als endothelin-antagonisten

Publications (1)

Publication Number	Publication Date
SK11512000A3 true SK11512000A3 (sk)	2001-04-09

Family

ID=7857948

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1151-2000A SK11512000A3 (sk)	1998-02-17	1999-02-05	5-substituované deriváty pyrimidín-2-yloxy karboxylových kyselín, ich príprava a ich využitie ako antagonistov endotelínu

Country Status (20)

Country	Link
EP (1)	EP1066268A1 (no)
JP (1)	JP2002503726A (no)
KR (1)	KR20010086247A (no)
CN (1)	CN1291190A (no)
AR (1)	AR014960A1 (no)
AU (1)	AU3027199A (no)
BG (1)	BG104577A (no)
BR (1)	BR9907911A (no)
CA (1)	CA2321182A1 (no)
DE (1)	DE19806438A1 (no)
HR (1)	HRP20000602A2 (no)
HU (1)	HUP0100957A3 (no)
IL (1)	IL137038A0 (no)
NO (1)	NO20004075D0 (no)
PL (1)	PL342311A1 (no)
SK (1)	SK11512000A3 (no)
TR (1)	TR200002376T2 (no)
TW (1)	TW579376B (no)
WO (1)	WO1999042453A1 (no)
ZA (1)	ZA991214B (no)

Families Citing this family (5)

* 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
US8168616B1 (en) *	2000-11-17	2012-05-01	Novartis Ag	Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension
JP2010535210A (ja)	2007-07-31	2010-11-18	ギリード・コロラド・インコーポレーテッド	アンブリセンタンの代謝産物および誘導体
HUE026195T2 (en) *	2008-01-22	2016-05-30	Dow Agrosciences Llc	4-Amino-5-fluoropyrimidine derivatives as fungicides
EP2647287A1 (en) *	2008-08-01	2013-10-09	Dow AgroSciences LLC	Use of 5-fluorocytosine and its derivatives as fungicides

Family Cites Families (7)

* 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
DE19614533A1 (de) *	1996-04-12	1997-10-16	Basf Ag	Neue alpha-Hydroxysäurederivate, ihre Herstellung und Verwendung
DE19614534A1 (de) *	1996-04-12	1997-10-16	Basf Ag	Neue Carbonsäurederivate, ihre Herstellung und Verwendung
KR20000057642A (ko) *	1996-12-18	2000-09-25	스타르크, 카르크	헤테로시클릭 카르복실산 유도체, 그의 제제 및 엔도텔린 수용체길항제로서의 용도
DE19726146A1 (de) *	1997-06-19	1998-12-24	Basf Ag	Neue ß-Amino und ß-Azidopcarbonsäurederivate, ihre Herstellung und Verwendung als Endothelinrezeptorantagonisten
NZ504316A (en) *	1997-10-31	2002-12-20	Basf Ag	Pyrimidine substituted carboxylic acid derivatives which have amido side-chains useful as endothelin receptor antagonists

1998
- 1998-02-17 DE DE19806438A patent/DE19806438A1/de not_active Withdrawn
1999
- 1999-02-05 TR TR2000/02376T patent/TR200002376T2/xx unknown
- 1999-02-05 CN CN99803037A patent/CN1291190A/zh active Pending
- 1999-02-05 EP EP99911657A patent/EP1066268A1/de not_active Withdrawn
- 1999-02-05 WO PCT/EP1999/000776 patent/WO1999042453A1/de not_active Ceased
- 1999-02-05 PL PL99342311A patent/PL342311A1/xx unknown
- 1999-02-05 CA CA002321182A patent/CA2321182A1/en not_active Abandoned
- 1999-02-05 SK SK1151-2000A patent/SK11512000A3/sk unknown
- 1999-02-05 KR KR1020007008925A patent/KR20010086247A/ko not_active Withdrawn
- 1999-02-05 JP JP2000532405A patent/JP2002503726A/ja active Pending
- 1999-02-05 AU AU30271/99A patent/AU3027199A/en not_active Abandoned
- 1999-02-05 HR HR20000602A patent/HRP20000602A2/hr not_active Application Discontinuation
- 1999-02-05 HU HU0100957A patent/HUP0100957A3/hu unknown
- 1999-02-05 IL IL13703899A patent/IL137038A0/xx unknown
- 1999-02-05 BR BR9907911-9A patent/BR9907911A/pt not_active IP Right Cessation
- 1999-02-10 TW TW088102031A patent/TW579376B/zh active
- 1999-02-16 ZA ZA9901214A patent/ZA991214B/xx unknown
- 1999-02-16 AR ARP990100634A patent/AR014960A1/es not_active Application Discontinuation
2000
- 2000-07-04 BG BG104577A patent/BG104577A/bg unknown
- 2000-08-15 NO NO20004075A patent/NO20004075D0/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CN1291190A (zh)	2001-04-11
AR014960A1 (es)	2001-04-11
HUP0100957A2 (hu)	2002-02-28
TW579376B (en)	2004-03-11
DE19806438A1 (de)	1999-08-19
BG104577A (bg)	2001-03-30
NO20004075L (no)	2000-08-15
NO20004075D0 (no)	2000-08-15
HRP20000602A2 (en)	2001-06-30
ZA991214B (en)	2000-08-16
PL342311A1 (en)	2001-06-04
KR20010086247A (ko)	2001-09-10
WO1999042453A1 (de)	1999-08-26
AU3027199A (en)	1999-09-06
JP2002503726A (ja)	2002-02-05
EP1066268A1 (de)	2001-01-10
BR9907911A (pt)	2000-10-24
TR200002376T2 (tr)	2000-12-21
HUP0100957A3 (en)	2002-03-28
CA2321182A1 (en)	1999-08-26
IL137038A0 (en)	2001-06-14

Publication	Publication Date	Title
SK25999A3 (en)	1999-09-10	Azinyloxy-and phenoxy-diaryl-carboxylic acid derivatives, their preparation and use as mixed eta/etb endothelin receptor antagonists
HRP980560A2 (en)	1999-08-31	New carboxylic acid derivatives, carrying amido side-chains, their production and use as endothelin receptor antagonists
SK77799A3 (en)	2000-02-14	Heterocyclic carboxylic acid derivatives, the production and use thereof as endothelin receptor antagonists
SK11512000A3 (sk)	2001-04-09	5-substituované deriváty pyrimidín-2-yloxy karboxylových kyselín, ich príprava a ich využitie ako antagonistov endotelínu
HRP980331A2 (en)	1999-02-28	New beta-amino and beta-azido carboxylic acid derivatives, the production and the use thereof as endothelin receptor antagonists
KR20010023615A (ko)	2001-03-26	신규 카르복실산 유도체, 그 제조 및 혼합 ｅｔａ/ｅｔｂ엔도텔린 수용체 길항제로서의 용도
HRP980591A2 (en)	1999-08-31	Novel heterocyclically substituted alpha-hydroxycarboxylic acid derivatives, their preparation and use as endothelin receptor antagonists
HUP0201321A2 (hu)	2002-12-28	Új béta-amido- és béta-szulfonamido-karbonsavszármazékok, előállításuk és a vegyületeket tartalmazó gyógyszerkészítmények
SK772002A3 (en)	2003-01-09	Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists
SK17552001A3 (sk)	2002-08-06	Deriváty karboxylových kyselín s arylsubstituovanými dusíkatými heterocyklami, ich príprava a použitie ako antagonistov endotelínového receptora
SK11752000A3 (sk)	2001-05-10	Nesymetricky substituované deriváty karboxylových kyselín, spôsob ich prípravy a ich použitie ako zmesových antagonistov eta/etb receptora
CZ20002963A3 (cs)	2000-11-15	Nové deriváty karboxylové kyseliny, obsahující 5- substituovaný pyrimidinový kruh, jejich příprava a použiti
CA2340167A1 (en)	2000-02-24	New carboxylic acid derivatives carrying keto side-chains, their production and their use as endothelin-receptor antagonists
MXPA00006463A (en)	2001-07-03	5-substituted pyrimidine-2-yloxy carboxylic acid derivatives, the production of the same and their utilization as endothelin antagonists
HRP970503A2 (en)	1999-06-30	Novel carboxylic acid derivatives, their production and their use as mixed eta/etb receptor antagonists
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
MXPA01001246A (en)	2001-09-07	New carboxylic acid derivatives carrying keto side-chains, their production and their use as endothelin-receptor antagonists
CZ2001437A3 (cs)	2001-05-16	Deriváty kyseliny karboxylové a jejich použití