BG61692B1 - Съединения с ангиотензин ii антагонистична активност - Google Patents
Съединения с ангиотензин ii антагонистична активност Download PDFInfo
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- BG61692B1 BG61692B1 BG98430A BG9843094A BG61692B1 BG 61692 B1 BG61692 B1 BG 61692B1 BG 98430 A BG98430 A BG 98430A BG 9843094 A BG9843094 A BG 9843094A BG 61692 B1 BG61692 B1 BG 61692B1
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- Prior art keywords
- methyl
- group
- formula
- butyl
- alkyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 47
- 230000003042 antagnostic effect Effects 0.000 title abstract description 5
- 102000005862 Angiotensin II Human genes 0.000 title description 3
- 101800000733 Angiotensin-2 Proteins 0.000 title description 3
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 title description 3
- 229950006323 angiotensin ii Drugs 0.000 title description 3
- -1 hydroxy, carboxy Chemical group 0.000 claims description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 14
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 12
- 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 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- ZEQBPZZTYKGYLB-UHFFFAOYSA-N methyl 2-[[4-butyl-2-methyl-6-oxo-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-1-yl]methyl]furan-3-carboxylate Chemical compound O=C1C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2NN=NN=2)=C(CCCC)N=C(C)N1CC=1OC=CC=1C(=O)OC ZEQBPZZTYKGYLB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
- WWQQLYKZONSZCD-UHFFFAOYSA-N 2-[[4-butyl-2-methyl-6-oxo-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-1-yl]methyl]furan-3-carboxylic acid Chemical compound O=C1C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C2=NNN=N2)=C(CCCC)N=C(C)N1CC=1OC=CC=1C(O)=O WWQQLYKZONSZCD-UHFFFAOYSA-N 0.000 claims 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 239000003480 eluent Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- WNAFVJVEADYQAI-UHFFFAOYSA-N methyl 2-phenylbenzoate Chemical group COC(=O)C1=CC=CC=C1C1=CC=CC=C1 WNAFVJVEADYQAI-UHFFFAOYSA-N 0.000 description 4
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-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
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- GHVZOJONCUEWAV-UHFFFAOYSA-N [K].CCO Chemical compound [K].CCO GHVZOJONCUEWAV-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- AFCZUIFDTUPEJW-UHFFFAOYSA-N methyl 2-[4-[(6-butyl-4-oxo-1h-pyrimidin-5-yl)methyl]phenyl]benzoate Chemical compound N1=CNC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(=O)OC)=C1CCCC AFCZUIFDTUPEJW-UHFFFAOYSA-N 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- RMXGTMRDXKUUDJ-UHFFFAOYSA-N methyl 2-[4-(bromomethyl)phenyl]benzoate Chemical group COC(=O)C1=CC=CC=C1C1=CC=C(CBr)C=C1 RMXGTMRDXKUUDJ-UHFFFAOYSA-N 0.000 description 2
- QLXGKRREECKWFY-UHFFFAOYSA-N methyl 2-[4-[(2-amino-6-butyl-4-oxo-1h-pyrimidin-5-yl)methyl]phenyl]benzoate Chemical compound N1=C(N)NC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(=O)OC)=C1CCCC QLXGKRREECKWFY-UHFFFAOYSA-N 0.000 description 2
- PONRPCIHEGPNCW-UHFFFAOYSA-N methyl 4-oxooctanoate Chemical compound CCCCC(=O)CCC(=O)OC PONRPCIHEGPNCW-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003536 tetrazoles Chemical group 0.000 description 2
- RBPHBLDGMYKMKY-BDVNFPICSA-N (2R,3R,4R,5S)-6-(methoxyamino)hexane-1,2,3,4,5-pentol Chemical compound CONC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO RBPHBLDGMYKMKY-BDVNFPICSA-N 0.000 description 1
- WJXAVNPIJIPGMN-PNGYUKAISA-N (2s)-2-[[(2s)-1-[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-methoxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]py Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(C)C)C1=CC=C(OC)C=C1 WJXAVNPIJIPGMN-PNGYUKAISA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- ALLIZEAXNXSFGD-UHFFFAOYSA-N 1-methyl-2-phenylbenzene Chemical group CC1=CC=CC=C1C1=CC=CC=C1 ALLIZEAXNXSFGD-UHFFFAOYSA-N 0.000 description 1
- HINYYXVJVFIOQS-UHFFFAOYSA-N 1-methyl-3-(6-oxo-1h-pyrimidin-2-yl)thiourea Chemical compound CNC(=S)NC1=NC=CC(=O)N1 HINYYXVJVFIOQS-UHFFFAOYSA-N 0.000 description 1
- GUMKKQWIFNVOMJ-UHFFFAOYSA-N 2-[4-[(2-amino-6-butyl-4-oxo-1h-pyrimidin-5-yl)methyl]phenyl]benzoic acid Chemical compound N1=C(N)NC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=C1CCCC GUMKKQWIFNVOMJ-UHFFFAOYSA-N 0.000 description 1
- IRJOKAICTQOELR-UHFFFAOYSA-N 2-[4-[(4-oxo-6-propyl-1h-pyrimidin-5-yl)methyl]phenyl]benzoic acid Chemical compound N1=CNC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=C1CCC IRJOKAICTQOELR-UHFFFAOYSA-N 0.000 description 1
- JUGDBWLPAFDFEL-UHFFFAOYSA-N 2-[4-[(6-butyl-2,4-dioxo-1h-pyrimidin-5-yl)methyl]phenyl]benzoic acid Chemical compound N1=C(O)NC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=C1CCCC JUGDBWLPAFDFEL-UHFFFAOYSA-N 0.000 description 1
- NDTZSKDYNBHALD-UHFFFAOYSA-N 2-[4-[(6-butyl-2-methyl-4-oxo-1h-pyrimidin-5-yl)methyl]phenyl]benzoic acid Chemical compound N1=C(C)NC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=C1CCCC NDTZSKDYNBHALD-UHFFFAOYSA-N 0.000 description 1
- LULRHOGSFJPVOO-UHFFFAOYSA-N 2-[4-[(6-butyl-2-nitramido-4-oxo-1h-pyrimidin-5-yl)methyl]phenyl]benzoic acid Chemical compound N1=C(N[N+]([O-])=O)NC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=C1CCCC LULRHOGSFJPVOO-UHFFFAOYSA-N 0.000 description 1
- YLRGOXYDVMJJBD-UHFFFAOYSA-N 2-[4-[(6-butyl-4-oxo-1h-pyrimidin-5-yl)methyl]phenyl]-4-chlorobenzoic acid Chemical compound N1=CNC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=C(Cl)C=2)C(O)=O)=C1CCCC YLRGOXYDVMJJBD-UHFFFAOYSA-N 0.000 description 1
- NKLPSTFCHFXHGB-UHFFFAOYSA-N 2-[4-[(6-butyl-4-oxo-1h-pyrimidin-5-yl)methyl]phenyl]benzoic acid Chemical compound N1=CNC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=C1CCCC NKLPSTFCHFXHGB-UHFFFAOYSA-N 0.000 description 1
- FCVYNDZGCOOLGH-UHFFFAOYSA-N 2-[4-[(6-butyl-4-oxo-1h-pyrimidin-5-yl)methyl]phenyl]benzonitrile Chemical compound N1=CNC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C#N)=C1CCCC FCVYNDZGCOOLGH-UHFFFAOYSA-N 0.000 description 1
- QDEPHLBJBBXYHQ-UHFFFAOYSA-N 2-[4-[[4-butyl-1-[(4-carboxyphenyl)methyl]-6-oxopyrimidin-5-yl]methyl]phenyl]benzoic acid Chemical compound O=C1C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=C(CCCC)N=CN1CC1=CC=C(C(O)=O)C=C1 QDEPHLBJBBXYHQ-UHFFFAOYSA-N 0.000 description 1
- PJSKZZKIEHUYTG-UHFFFAOYSA-N 2-[4-[[4-butyl-6-(methoxymethyl)-2-methylpyrimidin-5-yl]methyl]phenyl]benzoic acid Chemical compound CCCCC1=NC(C)=NC(COC)=C1CC1=CC=C(C=2C(=CC=CC=2)C(O)=O)C=C1 PJSKZZKIEHUYTG-UHFFFAOYSA-N 0.000 description 1
- KHZCRPBYBIUUJZ-UHFFFAOYSA-N 2-[4-[[4-butyl-6-[(4-carboxyphenyl)methoxymethyl]pyrimidin-5-yl]methyl]phenyl]benzoic acid Chemical compound C=1C=C(C=2C(=CC=CC=2)C(O)=O)C=CC=1CC=1C(CCCC)=NC=NC=1COCC1=CC=C(C(O)=O)C=C1 KHZCRPBYBIUUJZ-UHFFFAOYSA-N 0.000 description 1
- NDHMTAKGFSSBJJ-UHFFFAOYSA-N 2-[4-[[4-butyl-6-oxo-1-(thiophen-2-ylmethyl)pyrimidin-5-yl]methyl]phenyl]benzoic acid Chemical compound O=C1C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=C(CCCC)N=CN1CC1=CC=CS1 NDHMTAKGFSSBJJ-UHFFFAOYSA-N 0.000 description 1
- DKZRXGWFEFDCFY-UHFFFAOYSA-N 2-[4-[[6-butyl-2-(carbamoylamino)-4-oxo-1h-pyrimidin-5-yl]methyl]phenyl]benzoic acid Chemical compound N1=C(NC(N)=O)NC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=C1CCCC DKZRXGWFEFDCFY-UHFFFAOYSA-N 0.000 description 1
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- VIVROVBHWHOOMO-UHFFFAOYSA-N methyl 2-[[4-butyl-5-[[4-(2-methoxycarbonylphenyl)phenyl]methyl]-2-methyl-6-oxopyrimidin-1-yl]methyl]thiophene-3-carboxylate Chemical compound O=C1C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(=O)OC)=C(CCCC)N=C(C)N1CC=1SC=CC=1C(=O)OC VIVROVBHWHOOMO-UHFFFAOYSA-N 0.000 description 1
- DVEHRDSJFSWVRJ-UHFFFAOYSA-N methyl 2-[[4-butyl-5-[[4-(2-methoxycarbonylphenyl)phenyl]methyl]-6-oxopyrimidin-1-yl]methyl]benzoate Chemical compound O=C1C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(=O)OC)=C(CCCC)N=CN1CC1=CC=CC=C1C(=O)OC DVEHRDSJFSWVRJ-UHFFFAOYSA-N 0.000 description 1
- FPMUIWWMUSPQMK-UHFFFAOYSA-N methyl 2-[[6-butyl-2-methyl-5-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-4-yl]oxymethyl]benzoate Chemical compound C=1C=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=CC=1CC=1C(CCCC)=NC(C)=NC=1OCC1=CC=CC=C1C(=O)OC FPMUIWWMUSPQMK-UHFFFAOYSA-N 0.000 description 1
- QZMPVTZCXLHSMG-UHFFFAOYSA-N methyl 2-[[6-butyl-2-methyl-5-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-4-yl]oxymethyl]furan-3-carboxylate Chemical compound C=1C=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=CC=1CC=1C(CCCC)=NC(C)=NC=1OCC=1OC=CC=1C(=O)OC QZMPVTZCXLHSMG-UHFFFAOYSA-N 0.000 description 1
- FUNCORVGUBAJHF-UHFFFAOYSA-N methyl 2-[[6-butyl-2-methyl-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-4-yl]oxymethyl]benzoate Chemical compound C=1C=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=CC=1CC=1C(CCCC)=NC(C)=NC=1OCC1=CC=CC=C1C(=O)OC FUNCORVGUBAJHF-UHFFFAOYSA-N 0.000 description 1
- FELBEKBMMQEHDI-UHFFFAOYSA-N methyl 2-[[6-butyl-2-methyl-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-4-yl]oxymethyl]furan-3-carboxylate Chemical compound C=1C=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=CC=1CC=1C(CCCC)=NC(C)=NC=1OCC=1OC=CC=1C(=O)OC FELBEKBMMQEHDI-UHFFFAOYSA-N 0.000 description 1
- DXBKPKMMBZVGSC-UHFFFAOYSA-N methyl 2-[[6-butyl-2-methyl-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-4-yl]oxymethyl]thiophene-3-carboxylate Chemical compound C=1C=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=CC=1CC=1C(CCCC)=NC(C)=NC=1OCC=1SC=CC=1C(=O)OC DXBKPKMMBZVGSC-UHFFFAOYSA-N 0.000 description 1
- GPEZAFHLUIOPNK-UHFFFAOYSA-N methyl 2-[[6-butyl-5-[[4-(2-methoxycarbonylphenyl)phenyl]methyl]-2-methylpyrimidin-4-yl]oxymethyl]furan-3-carboxylate Chemical compound C=1C=C(C=2C(=CC=CC=2)C(=O)OC)C=CC=1CC=1C(CCCC)=NC(C)=NC=1OCC=1OC=CC=1C(=O)OC GPEZAFHLUIOPNK-UHFFFAOYSA-N 0.000 description 1
- PSCDQIQUMWGYCC-UHFFFAOYSA-N methyl 2-[[6-butyl-5-[[4-(2-methoxycarbonylphenyl)phenyl]methyl]-2-methylpyrimidin-4-yl]oxymethyl]thiophene-3-carboxylate Chemical compound C=1C=C(C=2C(=CC=CC=2)C(=O)OC)C=CC=1CC=1C(CCCC)=NC(C)=NC=1OCC=1SC=CC=1C(=O)OC PSCDQIQUMWGYCC-UHFFFAOYSA-N 0.000 description 1
- ZYZCGALAMPFMDG-UHFFFAOYSA-N methyl 2-[[6-butyl-5-[[4-(2-methoxycarbonylphenyl)phenyl]methyl]pyrimidin-4-yl]oxymethyl]benzoate Chemical compound C=1C=C(C=2C(=CC=CC=2)C(=O)OC)C=CC=1CC=1C(CCCC)=NC=NC=1OCC1=CC=CC=C1C(=O)OC ZYZCGALAMPFMDG-UHFFFAOYSA-N 0.000 description 1
- QNEIZSSWCVSZOS-UHFFFAOYSA-N methyl 2-phenylmethoxyacetate Chemical compound COC(=O)COCC1=CC=CC=C1 QNEIZSSWCVSZOS-UHFFFAOYSA-N 0.000 description 1
- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
- DGFINRONZNGFQN-UHFFFAOYSA-N methyl 4-[[6-butyl-2-methyl-5-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-4-yl]oxymethyl]benzoate Chemical compound C=1C=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=CC=1CC=1C(CCCC)=NC(C)=NC=1OCC1=CC=C(C(=O)OC)C=C1 DGFINRONZNGFQN-UHFFFAOYSA-N 0.000 description 1
- KSMSPPXRMSLFKO-UHFFFAOYSA-N methyl 4-oxoheptanoate Chemical compound CCCC(=O)CCC(=O)OC KSMSPPXRMSLFKO-UHFFFAOYSA-N 0.000 description 1
- GATUGNVDXMYTJX-UHFFFAOYSA-N methyl 4-phenylbenzoate Chemical group C1=CC(C(=O)OC)=CC=C1C1=CC=CC=C1 GATUGNVDXMYTJX-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- KVSYWEBLDGJZMB-UHFFFAOYSA-N n-[6-butyl-4-oxo-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-1h-pyrimidin-2-yl]acetamide Chemical compound N1C(NC(C)=O)=NC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C2=NNN=N2)=C1CCCC KVSYWEBLDGJZMB-UHFFFAOYSA-N 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- 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
-
- 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
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—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
- C07D403/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI912182A IT1250749B (it) | 1991-08-02 | 1991-08-02 | Composti eterociclici ad attivita' a ii antagonista |
PCT/EP1992/001753 WO1993003018A1 (en) | 1991-08-02 | 1992-08-03 | Compounds having angiotensine ii antagonistic activity |
Publications (2)
Publication Number | Publication Date |
---|---|
BG98430A BG98430A (bg) | 1994-09-30 |
BG61692B1 true BG61692B1 (bg) | 1998-03-31 |
Family
ID=11360517
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BG98430A BG61692B1 (bg) | 1991-08-02 | 1994-01-31 | Съединения с ангиотензин ii антагонистична активност |
Country Status (14)
Country | Link |
---|---|
US (1) | US5565464A (fi) |
EP (1) | EP0641329A1 (fi) |
JP (1) | JPH06509349A (fi) |
AU (1) | AU668357B2 (fi) |
BG (1) | BG61692B1 (fi) |
CA (1) | CA2114621A1 (fi) |
CZ (1) | CZ16994A3 (fi) |
FI (1) | FI940355A (fi) |
HU (1) | HUT67666A (fi) |
IT (1) | IT1250749B (fi) |
PL (1) | PL174986B1 (fi) |
RO (1) | RO113987B1 (fi) |
SK (1) | SK10694A3 (fi) |
WO (1) | WO1993003018A1 (fi) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100300566B1 (ko) * | 1994-09-17 | 2001-11-22 | 조생현 | 피리미디논유도체와그의제조방법및용도 |
IT1283620B1 (it) * | 1996-04-19 | 1998-04-22 | Luso Farmaco Inst | "pirimidin-4-oni n-3 sostituiti ad attivita' aii antagonista" |
CA2176058C (en) * | 1996-05-08 | 1999-03-02 | William Nicholas Goodway | Three-dimensional seismic acquisition |
NZ503407A (en) * | 1997-10-31 | 2002-08-28 | Aventis Pharma Ltd | Anilide derivatives useful for treating inflammatory diseases |
SE9903028D0 (sv) | 1999-08-27 | 1999-08-27 | Astra Ab | New use |
EP1668008A4 (en) * | 2003-08-28 | 2009-02-25 | Nitromed Inc | NITROSED AND NITROSYLATED DIETETIC COMPOUNDS, COMPOSITIONS AND APPLICATION METHODS |
CA2597463A1 (en) * | 2005-02-28 | 2006-09-08 | Nitromed, Inc. | Cardiovascular compounds comprising nitric oxide enhancing groups, compositions and methods of use |
CA2597444A1 (en) * | 2005-03-09 | 2006-09-21 | Nitromed, Inc. | Organic nitric oxide enhancing salts of angiotensin ii antagonists, compositions and methods of use |
US20060281712A1 (en) * | 2005-06-14 | 2006-12-14 | Chi-Feng Yen | Pyrimidine compounds |
US8193206B2 (en) | 2005-06-14 | 2012-06-05 | Taigen Biotechnology Co., Ltd. | Pyrimidine compounds |
US20080207654A1 (en) * | 2006-11-24 | 2008-08-28 | Takeda Pharmaceutical Company Limited | Heteromonocyclic compound and use thereof |
US7803940B2 (en) * | 2006-11-24 | 2010-09-28 | Takeda Pharmaceutical Company Limited | Heteromonocyclic compound or a salt thereof having strong antihypertensive action, insulin sensitizing activity and the like production thereof and use thereof for prophylaxis or treatment of cardiovascular diseases, metabolic diseases and/or central nervous system diseases |
MX354786B (es) | 2007-06-04 | 2018-03-21 | Synergy Pharmaceuticals Inc | Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos. |
US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
EP3239170B1 (en) | 2008-06-04 | 2019-03-20 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
EP3241839B1 (en) | 2008-07-16 | 2019-09-04 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
ES2433225T3 (es) | 2009-01-30 | 2013-12-10 | Takeda Pharmaceutical Company Limited | Compuesto con anillos condensados y uso del mismo |
US8664226B2 (en) | 2009-04-17 | 2014-03-04 | Kowa Company, Ltd. | Compound having 3-heteroarylpyrimidin-4-(3H)-one structure and pharmaceutical preparation containing same |
US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
CA2905435A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
JP2016514671A (ja) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼのアゴニストおよびその使用 |
EP3004138B1 (en) | 2013-06-05 | 2024-03-13 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
KR102131022B1 (ko) * | 2018-07-12 | 2020-07-07 | 보령제약 주식회사 | 피리미디논 유도체 화합물 및 이의 용도 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0424317A3 (en) * | 1989-10-19 | 1991-09-25 | Ciba-Geigy Ag | Pyrimidines |
EP0435827A3 (en) * | 1989-12-28 | 1991-11-13 | Ciba-Geigy Ag | Diaza compounds |
US5166206A (en) * | 1990-03-30 | 1992-11-24 | Merck & Co., Inc. | Substituted pyrimidines, pyrimidinones and pyridopyrimidines |
WO1991015209A1 (en) * | 1990-03-30 | 1991-10-17 | Merck & Co., Inc. | Substituted pyrimidines, pyrimidinones and pyridopyrimidines |
IE912114A1 (en) * | 1990-07-02 | 1992-01-15 | Union Pharma Scient Appl | Novel pyrimidine derivatives which are angiotensin ii¹receptor antagonists, their methods of preparation and¹pharmaceutical compositions in which they are present |
-
1991
- 1991-08-02 IT ITMI912182A patent/IT1250749B/it active IP Right Grant
-
1992
- 1992-08-03 PL PL92302346A patent/PL174986B1/pl unknown
- 1992-08-03 RO RO94-00144A patent/RO113987B1/ro unknown
- 1992-08-03 CA CA002114621A patent/CA2114621A1/en not_active Abandoned
- 1992-08-03 EP EP92916506A patent/EP0641329A1/en not_active Withdrawn
- 1992-08-03 CZ CZ94169A patent/CZ16994A3/cs unknown
- 1992-08-03 WO PCT/EP1992/001753 patent/WO1993003018A1/en not_active Application Discontinuation
- 1992-08-03 HU HU9400267A patent/HUT67666A/hu unknown
- 1992-08-03 US US08/193,025 patent/US5565464A/en not_active Expired - Fee Related
- 1992-08-03 AU AU23873/92A patent/AU668357B2/en not_active Ceased
- 1992-08-03 SK SK106-94A patent/SK10694A3/sk unknown
- 1992-08-03 JP JP5503271A patent/JPH06509349A/ja active Pending
-
1994
- 1994-01-25 FI FI940355A patent/FI940355A/fi unknown
- 1994-01-31 BG BG98430A patent/BG61692B1/bg unknown
Also Published As
Publication number | Publication date |
---|---|
EP0641329A1 (en) | 1995-03-08 |
BG98430A (bg) | 1994-09-30 |
JPH06509349A (ja) | 1994-10-20 |
US5565464A (en) | 1996-10-15 |
AU2387392A (en) | 1993-03-02 |
HUT67666A (en) | 1995-04-28 |
PL174986B1 (pl) | 1998-10-30 |
ITMI912182A0 (it) | 1991-08-02 |
RO113987B1 (ro) | 1998-12-30 |
FI940355A0 (fi) | 1994-01-25 |
ITMI912182A1 (it) | 1993-02-03 |
FI940355A (fi) | 1994-01-25 |
AU668357B2 (en) | 1996-05-02 |
IT1250749B (it) | 1995-04-21 |
CA2114621A1 (en) | 1993-02-18 |
CZ16994A3 (en) | 1994-06-15 |
WO1993003018A1 (en) | 1993-02-18 |
HU9400267D0 (en) | 1994-05-30 |
SK10694A3 (en) | 1994-12-07 |
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