NO310235B1 - Pyrimidin-derivater, anvendelse av dem og farmasöytiske blandinger inneholdende dem - Google Patents
Pyrimidin-derivater, anvendelse av dem og farmasöytiske blandinger inneholdende dem Download PDFInfo
- Publication number
- NO310235B1 NO310235B1 NO19980959A NO980959A NO310235B1 NO 310235 B1 NO310235 B1 NO 310235B1 NO 19980959 A NO19980959 A NO 19980959A NO 980959 A NO980959 A NO 980959A NO 310235 B1 NO310235 B1 NO 310235B1
- Authority
- NO
- Norway
- Prior art keywords
- methoxyphenoxy
- compound
- synthesis
- butyl
- butylphenylsulfonylamino
- Prior art date
Links
- 150000003230 pyrimidines Chemical class 0.000 title claims description 20
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 4
- 239000008194 pharmaceutical composition Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 86
- 239000000203 mixture Substances 0.000 claims description 21
- 102000002045 Endothelin Human genes 0.000 claims description 16
- 108050009340 Endothelin Proteins 0.000 claims description 16
- 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 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 230000006806 disease prevention Effects 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 description 61
- 238000003786 synthesis reaction Methods 0.000 description 61
- 238000000034 method Methods 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 35
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- BJDRYJYMAAHUMV-UHFFFAOYSA-N 4-tert-butyl-n-[2,6-dichloro-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(Cl)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 BJDRYJYMAAHUMV-UHFFFAOYSA-N 0.000 description 18
- -1 methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexyloxy, cyclo-propyloxy Chemical group 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- SVOAIOVXJLQROO-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]oxypropanoic acid Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCOCC2)OCCC(O)=O)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 SVOAIOVXJLQROO-UHFFFAOYSA-N 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- YKOLZVXSPGIIBJ-UHFFFAOYSA-N 2-Isopropylaniline Chemical compound CC(C)C1=CC=CC=C1N YKOLZVXSPGIIBJ-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 5
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 5
- 229940035437 1,3-propanediol Drugs 0.000 description 5
- CYLUEYOOGWPYGE-UHFFFAOYSA-N 2,4,6-trichloro-5-(2-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(Cl)N=C1Cl CYLUEYOOGWPYGE-UHFFFAOYSA-N 0.000 description 5
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- QPUXZGQASDDLMQ-UHFFFAOYSA-N diethyl 2-(2-methoxyphenoxy)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)OC1=CC=CC=C1OC QPUXZGQASDDLMQ-UHFFFAOYSA-N 0.000 description 5
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 208000019423 liver disease Diseases 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 210000002376 aorta thoracic Anatomy 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
- 229910000105 potassium hydride Inorganic materials 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 3
- 229940080818 propionamide Drugs 0.000 description 3
- BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 2
- UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical compound CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- MLPVBIWIRCKMJV-UHFFFAOYSA-N 2-ethylaniline Chemical compound CCC1=CC=CC=C1N MLPVBIWIRCKMJV-UHFFFAOYSA-N 0.000 description 2
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
- CBZHNVGORVQJCH-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-(4-phenylpiperazin-1-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(N2CCN(CC2)C=2C=CC=CC=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 CBZHNVGORVQJCH-UHFFFAOYSA-N 0.000 description 2
- BJYATIGZOWMIHX-UHFFFAOYSA-N 4-tert-butylbenzenesulfonamide;potassium Chemical compound [K].CC(C)(C)C1=CC=C(S(N)(=O)=O)C=C1 BJYATIGZOWMIHX-UHFFFAOYSA-N 0.000 description 2
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- 206010002388 Angina unstable Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- 208000033626 Renal failure acute Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 2
- 208000007814 Unstable Angina Diseases 0.000 description 2
- 206010047163 Vasospasm Diseases 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 201000011040 acute kidney failure Diseases 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical compound ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 201000005577 familial hyperlipidemia Diseases 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 201000004240 prostatic hypertrophy Diseases 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 206010038464 renal hypertension Diseases 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- LVLAOBPYNHXWRP-UHFFFAOYSA-N tert-butyl 4-[4-[(4-tert-butylphenyl)sulfonylamino]-6-(3-hydroxypropoxy)-5-(2-methoxyphenoxy)pyrimidin-2-yl]piperazine-1-carboxylate Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C(=O)OC(C)(C)C)OCCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 LVLAOBPYNHXWRP-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 231100000216 vascular lesion Toxicity 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- PMHUSCHKTSTQEP-UHFFFAOYSA-N (4-carbamimidoylphenyl)methanesulfonyl fluoride Chemical compound NC(=N)C1=CC=C(CS(F)(=O)=O)C=C1 PMHUSCHKTSTQEP-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- MSSDTZLYNMFTKN-UHFFFAOYSA-N 1-Piperazinecarboxaldehyde Chemical compound O=CN1CCNCC1 MSSDTZLYNMFTKN-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 1
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 1
- USDXFGRJDMOKCD-UHFFFAOYSA-N 2-[6-[(4-tert-butylphenyl)sulfonylamino]-2-(4-formylpiperazin-1-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxy-n-(1-phenylethyl)acetamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C=O)OCC(=O)NC(C)C=2C=CC=CC=2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 USDXFGRJDMOKCD-UHFFFAOYSA-N 0.000 description 1
- ARRQTQPXBFGMPQ-UHFFFAOYSA-N 2-hydroxy-n-(1-phenylethyl)acetamide Chemical compound OCC(=O)NC(C)C1=CC=CC=C1 ARRQTQPXBFGMPQ-UHFFFAOYSA-N 0.000 description 1
- MWOOKDULMBMMPN-UHFFFAOYSA-N 3-(2-ethyl-1,2-oxazol-2-ium-5-yl)benzenesulfonate Chemical compound O1[N+](CC)=CC=C1C1=CC=CC(S([O-])(=O)=O)=C1 MWOOKDULMBMMPN-UHFFFAOYSA-N 0.000 description 1
- WXQHABUKXNUYBA-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-2-(4-formylpiperazin-1-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxy-n-(2-propan-2-ylphenyl)propanamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C=O)OCCC(=O)NC=2C(=CC=CC=2)C(C)C)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 WXQHABUKXNUYBA-UHFFFAOYSA-N 0.000 description 1
- RESQCZPNTZSJTQ-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-2-(4-formylpiperazin-1-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxypropanoic acid Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C=O)OCCC(O)=O)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 RESQCZPNTZSJTQ-UHFFFAOYSA-N 0.000 description 1
- AARCRCYIDRIYLP-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxy-n-(2-propan-2-ylphenyl)propanamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(C)CC2)OCCC(=O)NC=2C(=CC=CC=2)C(C)C)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 AARCRCYIDRIYLP-UHFFFAOYSA-N 0.000 description 1
- UPFNLRQLVDGILP-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxypropanoic acid Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(C)CC2)OCCC(O)=O)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 UPFNLRQLVDGILP-UHFFFAOYSA-N 0.000 description 1
- UZPJAUHWDUKWIH-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-(4-phenylpiperazin-1-yl)pyrimidin-4-yl]oxy-n-(2-propan-2-ylphenyl)propanamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C=2C=CC=CC=2)OCCC(=O)NC=2C(=CC=CC=2)C(C)C)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 UZPJAUHWDUKWIH-UHFFFAOYSA-N 0.000 description 1
- MIIWKFAEUIXCOE-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-(4-phenylpiperazin-1-yl)pyrimidin-4-yl]oxypropanoic acid Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C=2C=CC=CC=2)OCCC(O)=O)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 MIIWKFAEUIXCOE-UHFFFAOYSA-N 0.000 description 1
- UAJVLSRFFVLXFM-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-(4-propan-2-ylpiperazin-1-yl)pyrimidin-4-yl]oxy-n-(2-propan-2-ylphenyl)propanamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C(C)C)OCCC(=O)NC=2C(=CC=CC=2)C(C)C)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 UAJVLSRFFVLXFM-UHFFFAOYSA-N 0.000 description 1
- CYXLTHYWLHBEDR-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-(4-propan-2-ylpiperazin-1-yl)pyrimidin-4-yl]oxypropanoic acid Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C(C)C)OCCC(O)=O)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 CYXLTHYWLHBEDR-UHFFFAOYSA-N 0.000 description 1
- CYWAEXCRNBZZMK-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]pyrimidin-4-yl]oxypropanoic acid Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C(=O)OC(C)(C)C)OCCC(O)=O)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 CYWAEXCRNBZZMK-UHFFFAOYSA-N 0.000 description 1
- NTSDNHCKMCVINH-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]oxy-n-(2,6-dimethylphenyl)propanamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCOCC2)OCCC(=O)NC=2C(=CC=CC=2C)C)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 NTSDNHCKMCVINH-UHFFFAOYSA-N 0.000 description 1
- FLGNFEVULXDPPD-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]oxy-n-(2-ethylphenyl)propanamide Chemical compound CCC1=CC=CC=C1NC(=O)CCOC1=NC(N2CCOCC2)=NC(NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1OC1=CC=CC=C1OC FLGNFEVULXDPPD-UHFFFAOYSA-N 0.000 description 1
- ARJIMTAIQDPCRI-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]oxy-n-(2-methoxyphenyl)propanamide Chemical compound COC1=CC=CC=C1NC(=O)CCOC1=NC(N2CCOCC2)=NC(NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1OC1=CC=CC=C1OC ARJIMTAIQDPCRI-UHFFFAOYSA-N 0.000 description 1
- CWEZGWLWCRPFKD-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]oxy-n-(4-propan-2-ylphenyl)propanamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCOCC2)OCCC(=O)NC=2C=CC(=CC=2)C(C)C)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 CWEZGWLWCRPFKD-UHFFFAOYSA-N 0.000 description 1
- ZAQQMTWVBUIRSB-UHFFFAOYSA-N 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]oxy-n-pyridin-2-ylpropanamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCOCC2)OCCC(=O)NC=2N=CC=CC=2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 ZAQQMTWVBUIRSB-UHFFFAOYSA-N 0.000 description 1
- XCCNRBCNYGWTQX-UHFFFAOYSA-N 3-propan-2-ylaniline Chemical compound CC(C)C1=CC=CC(N)=C1 XCCNRBCNYGWTQX-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- LHJQTCLFIWRZON-UHFFFAOYSA-N 4-tert-butyl-n-[2-(4-formylpiperazin-1-yl)-6-(3-hydroxypropoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C=O)OCCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 LHJQTCLFIWRZON-UHFFFAOYSA-N 0.000 description 1
- MDCOTNMXCPJEHZ-UHFFFAOYSA-N 4-tert-butyl-n-[6-(3-hydroxypropoxy)-5-(2-methoxyphenoxy)-2-(4-methyl-1,4-diazepan-1-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(C)CCC2)OCCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 MDCOTNMXCPJEHZ-UHFFFAOYSA-N 0.000 description 1
- QWJBEHSIELFQLA-UHFFFAOYSA-N 4-tert-butyl-n-[6-(3-hydroxypropoxy)-5-(2-methoxyphenoxy)-2-(4-phenylpiperazin-1-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C=2C=CC=CC=2)OCCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 QWJBEHSIELFQLA-UHFFFAOYSA-N 0.000 description 1
- BTYLDYPMEOQXOA-UHFFFAOYSA-N 4-tert-butyl-n-[6-(3-hydroxypropoxy)-5-(2-methoxyphenoxy)-2-(4-propan-2-ylpiperazin-1-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C(C)C)OCCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 BTYLDYPMEOQXOA-UHFFFAOYSA-N 0.000 description 1
- JCIAVMVIKOXHRA-UHFFFAOYSA-N 4-tert-butyl-n-[6-(3-hydroxypropoxy)-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCOCC2)OCCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 JCIAVMVIKOXHRA-UHFFFAOYSA-N 0.000 description 1
- NSDSLXLNBBTFJC-UHFFFAOYSA-N 4-tert-butyl-n-[6-(3-hydroxypropoxy)-5-(2-methoxyphenoxy)-2-piperazin-1-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCNCC2)OCCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 NSDSLXLNBBTFJC-UHFFFAOYSA-N 0.000 description 1
- DWWZHJJNZCVPKZ-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-2-(4-formylpiperazin-1-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(N2CCN(CC2)C=O)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 DWWZHJJNZCVPKZ-UHFFFAOYSA-N 0.000 description 1
- DJBHIQBVZAGROQ-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-(4-methyl-1,4-diazepan-1-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(N2CCN(C)CCC2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 DJBHIQBVZAGROQ-UHFFFAOYSA-N 0.000 description 1
- SXPLWZDWSMYOJZ-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-(4-propan-2-ylpiperazin-1-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(N2CCN(CC2)C(C)C)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 SXPLWZDWSMYOJZ-UHFFFAOYSA-N 0.000 description 1
- HRJLMERCLOMWGR-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(N2CCOCC2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HRJLMERCLOMWGR-UHFFFAOYSA-N 0.000 description 1
- ISDDAMUDYJWYQH-UHFFFAOYSA-N 5-(2-methoxyphenoxy)-1,3-diazinane-2,4,6-trione Chemical compound COC1=CC=CC=C1OC1C(=O)NC(=O)NC1=O ISDDAMUDYJWYQH-UHFFFAOYSA-N 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004129 EU approved improving agent Substances 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical class ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000026723 Urinary tract disease Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- YKZUBAOVJZXLQY-UHFFFAOYSA-N benzyl 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]oxypropanoate Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCOCC2)OCCC(=O)OCC=2C=CC=CC=2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 YKZUBAOVJZXLQY-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical compound [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 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 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- LXMCUXMHIFIVLK-UHFFFAOYSA-N methyl 3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-morpholin-4-ylpyrimidin-4-yl]oxypropanoate Chemical compound C=1C=CC=C(OC)C=1OC=1C(OCCC(=O)OC)=NC(N2CCOCC2)=NC=1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 LXMCUXMHIFIVLK-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- LRTFPLFDLJYEKT-UHFFFAOYSA-N para-isopropylaniline Chemical compound CC(C)C1=CC=C(N)C=C1 LRTFPLFDLJYEKT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- OZIWEYQVUCTOIU-UHFFFAOYSA-K sodium;trichlororuthenium Chemical compound [Na].Cl[Ru](Cl)Cl OZIWEYQVUCTOIU-UHFFFAOYSA-K 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- UYQCMUNLWYSDCN-UHFFFAOYSA-N tert-butyl 4-[4-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-6-[3-oxo-3-(2-propan-2-ylanilino)propoxy]pyrimidin-2-yl]piperazine-1-carboxylate Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)N2CCN(CC2)C(=O)OC(C)(C)C)OCCC(=O)NC=2C(=CC=CC=2)C(C)C)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 UYQCMUNLWYSDCN-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- WRTMQOHKMFDUKX-UHFFFAOYSA-N triiodide Chemical compound I[I-]I WRTMQOHKMFDUKX-UHFFFAOYSA-N 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 208000014001 urinary system disease Diseases 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen 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
- C07D239/52—Two oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22890795 | 1995-09-06 | ||
| PCT/JP1996/002494 WO1997009318A1 (fr) | 1995-09-06 | 1996-09-04 | Derives de la pyrimidine |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO980959L NO980959L (no) | 1998-03-05 |
| NO980959D0 NO980959D0 (no) | 1998-03-05 |
| NO310235B1 true NO310235B1 (no) | 2001-06-11 |
Family
ID=16883731
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19980959A NO310235B1 (no) | 1995-09-06 | 1998-03-05 | Pyrimidin-derivater, anvendelse av dem og farmasöytiske blandinger inneholdende dem |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5883092A (ja) |
| EP (1) | EP0852226B1 (ja) |
| KR (1) | KR100453097B1 (ja) |
| CN (1) | CN1105711C (ja) |
| AT (1) | ATE254607T1 (ja) |
| AU (1) | AU703892B2 (ja) |
| CA (1) | CA2230516C (ja) |
| DE (1) | DE69630799T2 (ja) |
| ES (1) | ES2210384T3 (ja) |
| HK (1) | HK1016591A1 (ja) |
| HU (1) | HUP9903526A3 (ja) |
| NO (1) | NO310235B1 (ja) |
| PT (1) | PT852226E (ja) |
| RU (1) | RU2170734C2 (ja) |
| WO (1) | WO1997009318A1 (ja) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2207100C (en) | 1994-12-28 | 2008-02-19 | Kowa Co., Ltd. | Pyrimidine derivatives |
| KR100388506B1 (ko) * | 1998-03-31 | 2003-06-25 | 다나베 세이야꾸 가부시키가이샤 | 배뇨장애의 예방·치료제 |
| CA2315614C (en) * | 1999-07-29 | 2004-11-02 | Pfizer Inc. | Pyrazoles |
| JP3751882B2 (ja) * | 2000-01-25 | 2006-03-01 | エフ．ホフマン−ラ ロシュ アーゲー | スルホンアミドの製造 |
| US6387915B2 (en) | 2000-05-31 | 2002-05-14 | Pfizer Inc. | Isoxazole-sulfonamide endothelin antagonists |
| US6670362B2 (en) | 2000-09-20 | 2003-12-30 | Pfizer Inc. | Pyridazine endothelin antagonists |
| WO2003099773A1 (en) | 2002-05-24 | 2003-12-04 | Millennium Pharmaceuticals, Inc. | Ccr9 inhibitors and methods of use thereof |
| WO2011078143A1 (ja) * | 2009-12-22 | 2011-06-30 | 塩野義製薬株式会社 | ピリミジン誘導体およびそれらを含有する医薬組成物 |
| CN105246877A (zh) | 2013-05-31 | 2016-01-13 | 兴和株式会社 | 具有二苄胺结构的嘧啶化合物的新形态 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW394761B (en) * | 1993-06-28 | 2000-06-21 | Hoffmann La Roche | Novel Sulfonylamino Pyrimidines |
| IL111959A (en) * | 1993-12-17 | 2000-07-16 | Tanabe Seiyaku Co | N-(polysubstituted pyrimidin-4-yl) benzenesulfonamide derivatives their preparation and pharmaceutical compositions containing them |
| CA2207100C (en) * | 1994-12-28 | 2008-02-19 | Kowa Co., Ltd. | Pyrimidine derivatives |
-
1996
- 1996-09-04 US US09/029,244 patent/US5883092A/en not_active Expired - Fee Related
- 1996-09-04 AU AU68890/96A patent/AU703892B2/en not_active Ceased
- 1996-09-04 CN CN96196812A patent/CN1105711C/zh not_active Expired - Fee Related
- 1996-09-04 DE DE69630799T patent/DE69630799T2/de not_active Expired - Lifetime
- 1996-09-04 WO PCT/JP1996/002494 patent/WO1997009318A1/ja active IP Right Grant
- 1996-09-04 KR KR10-1998-0701163A patent/KR100453097B1/ko not_active IP Right Cessation
- 1996-09-04 RU RU98106104/04A patent/RU2170734C2/ru not_active IP Right Cessation
- 1996-09-04 ES ES96929512T patent/ES2210384T3/es not_active Expired - Lifetime
- 1996-09-04 PT PT96929512T patent/PT852226E/pt unknown
- 1996-09-04 AT AT96929512T patent/ATE254607T1/de not_active IP Right Cessation
- 1996-09-04 HU HU9903526A patent/HUP9903526A3/hu unknown
- 1996-09-04 EP EP96929512A patent/EP0852226B1/en not_active Expired - Lifetime
- 1996-09-04 CA CA002230516A patent/CA2230516C/en not_active Expired - Fee Related
-
1998
- 1998-03-05 NO NO19980959A patent/NO310235B1/no not_active IP Right Cessation
-
1999
- 1999-04-13 HK HK99101534A patent/HK1016591A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NO980959L (no) | 1998-03-05 |
| US5883092A (en) | 1999-03-16 |
| ES2210384T3 (es) | 2004-07-01 |
| DE69630799T2 (de) | 2004-08-12 |
| DE69630799D1 (en) | 2003-12-24 |
| ATE254607T1 (de) | 2003-12-15 |
| KR19990037684A (ko) | 1999-05-25 |
| CN1105711C (zh) | 2003-04-16 |
| HUP9903526A2 (hu) | 2000-06-28 |
| AU703892B2 (en) | 1999-04-01 |
| EP0852226A4 (en) | 1998-09-02 |
| WO1997009318A1 (fr) | 1997-03-13 |
| NO980959D0 (no) | 1998-03-05 |
| CA2230516C (en) | 2008-11-18 |
| CN1196051A (zh) | 1998-10-14 |
| HUP9903526A3 (en) | 2000-07-28 |
| PT852226E (pt) | 2004-03-31 |
| EP0852226B1 (en) | 2003-11-19 |
| HK1016591A1 (en) | 1999-11-05 |
| KR100453097B1 (ko) | 2004-12-31 |
| RU2170734C2 (ru) | 2001-07-20 |
| CA2230516A1 (en) | 1997-03-13 |
| AU6889096A (en) | 1997-03-27 |
| EP0852226A1 (en) | 1998-07-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6335332B1 (en) | Barbituric acid derivatives with antimetastatic and antitumor activity | |
| JP2014525443A (ja) | キヌレニン−３−モノオキシゲナーゼインヒビター、医薬組成物、およびこれらの使用方法 | |
| CA2853024C (en) | 2-thiopyrimidinones | |
| NZ242396A (en) | 6-hydroxyalkoxy-pyrimidin-4-yl benzenesulphonamide derivatives; pharmaceutical compositions and preparatory processes | |
| NO310235B1 (no) | Pyrimidin-derivater, anvendelse av dem og farmasöytiske blandinger inneholdende dem | |
| WO1999025712A1 (fr) | Nouveaux composes d'amide et medicaments contenant ces derniers | |
| RU2201928C1 (ru) | 4-гетероциклилсульфонамидил-6-метокси-5-(2-метоксифенокси)-2-пиридилпиримидиновые производные и фармацевтическая композиция | |
| JP2001521927A (ja) | アミド側鎖を有する新規のカルボン酸誘導体、その製造およびエンドセリン受容体アンタゴニストとしての使用 | |
| EP0044704A1 (en) | Substituted pyrimidin-2-ones, the salts thereof, processes for their preparation, and pharmaceutical compositions containing them | |
| IE921330A1 (en) | 4-aryl-3-(heteroarylureido)quinoline derivatives | |
| EP0801062B1 (en) | Pyrimidine derivatives | |
| JP3728028B2 (ja) | ピリミジン誘導体 | |
| JPH11513677A (ja) | 新規免疫抑制及び抗ウイルス医薬剤としての脂質アルコール | |
| JP2000143637A (ja) | ピリミジン誘導体及びその製造法 | |
| JPH1143482A (ja) | ピリミジン誘導体 | |
| MXPA99011992A (en) | Barbituric acid derivatives with antimetastatic and antitumor activity | |
| Berber et al. | Selective synthesis of fluorinated benzyl-or phenylpyrimidines from the heterocyclisation of α-trifluoroacetylarylpropanenitriles | |
| KR20010031650A (ko) | 아마이도 측쇄를 가지는 신규한 카르복실산 유도체, 그의제법 및 엔도셀린 수용체 길항제로서의 용도 | |
| DE19809376A1 (de) | Neue Carbonsäurederivate, die Amidseitenketten tragen, ihre Herstellung und Verwendung als Endothelin-Rezeptorantagonisten | |
| CZ20001582A3 (cs) | Nové deriváty karboxylové kyseliny nesoucí amidový řetězec, způsob přípravy a použití jako antagonistů receptoru endothelínu | |
| JPH05262774A (ja) | ピロロ［３，２−ｅピラゾロ［１，５−ａピリミジン誘導体及びこれを含有する循環器系疾患治療剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |