CA1256107A - Pyrimidine derivatives, preparation thereof and use thereof - Google Patents
Pyrimidine derivatives, preparation thereof and use thereofInfo
- Publication number
- CA1256107A CA1256107A CA000450076A CA450076A CA1256107A CA 1256107 A CA1256107 A CA 1256107A CA 000450076 A CA000450076 A CA 000450076A CA 450076 A CA450076 A CA 450076A CA 1256107 A CA1256107 A CA 1256107A
- Authority
- CA
- Canada
- Prior art keywords
- compound
- alkyl
- lower alkyl
- phenyl
- optionally substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title abstract description 13
- 150000003230 pyrimidines Chemical class 0.000 title abstract description 12
- 238000002360 preparation method Methods 0.000 title abstract description 7
- -1 hydroxy, amino Chemical group 0.000 claims abstract description 121
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 114
- 150000003839 salts Chemical class 0.000 claims abstract description 87
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 44
- 239000001257 hydrogen Substances 0.000 claims abstract description 44
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 37
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 30
- 239000004593 Epoxy Substances 0.000 claims abstract description 28
- 229910052736 halogen Chemical group 0.000 claims abstract description 18
- 150000002367 halogens Chemical group 0.000 claims abstract description 18
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 150000002431 hydrogen Chemical class 0.000 claims abstract 15
- 150000001875 compounds Chemical class 0.000 claims description 120
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- IJJUENQVHOKTHU-UHFFFAOYSA-N C1=C(OC)C(OC)=CC=C1C(NC(=O)N1C)=CC1=NC1=C(C)C=C(C)C=C1C Chemical compound C1=C(OC)C(OC)=CC=C1C(NC(=O)N1C)=CC1=NC1=C(C)C=C(C)C=C1C IJJUENQVHOKTHU-UHFFFAOYSA-N 0.000 claims description 5
- WLUQFKLDOJWLIN-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)-1,3-dimethyl-6-(2,4,6-trimethylphenyl)iminopyrimidin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1C(N(C(=O)N1C)C)=CC1=NC1=C(C)C=C(C)C=C1C WLUQFKLDOJWLIN-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 4
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- NFHSJMMFPWGVHO-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)-1,3-dimethyl-6-(2,4,6-trimethoxyphenyl)iminopyrimidin-2-one Chemical compound COC1=CC(OC)=CC(OC)=C1N=C1N(C)C(=O)N(C)C(C=2C=C(OC)C(OC)=CC=2)=C1 NFHSJMMFPWGVHO-UHFFFAOYSA-N 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000005808 2,4,6-trimethoxyphenyl group Chemical group [H][#6]-1=[#6](-[#8]C([H])([H])[H])-[#6](-*)=[#6](-[#8]C([H])([H])[H])-[#6]([H])=[#6]-1-[#8]C([H])([H])[H] 0.000 claims 1
- YNLQYELKKUHQNR-UHFFFAOYSA-N 6-(3,4-dimethoxyphenyl)-2-ethoxy-3-methyl-n-(2,4,6-trimethylphenyl)pyrimidin-4-imine Chemical compound CN1C(OCC)=NC(C=2C=C(OC)C(OC)=CC=2)=CC1=NC1=C(C)C=C(C)C=C1C YNLQYELKKUHQNR-UHFFFAOYSA-N 0.000 claims 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 38
- 125000003118 aryl group Chemical group 0.000 abstract description 9
- 230000003177 cardiotonic effect Effects 0.000 abstract description 7
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 6
- 229940030600 antihypertensive agent Drugs 0.000 abstract description 3
- 239000002220 antihypertensive agent Substances 0.000 abstract description 3
- 229940127218 antiplatelet drug Drugs 0.000 abstract description 3
- 229940124549 vasodilator Drugs 0.000 abstract description 3
- 239000003071 vasodilator agent Substances 0.000 abstract description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 88
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- 238000006243 chemical reaction Methods 0.000 description 43
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 41
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 38
- 101150041968 CDC13 gene Proteins 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 230000002829 reductive effect Effects 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 27
- 239000002244 precipitate Substances 0.000 description 25
- 239000000243 solution Substances 0.000 description 23
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- KWVPRPSXBZNOHS-UHFFFAOYSA-N 2,4,6-Trimethylaniline Chemical compound CC1=CC(C)=C(N)C(C)=C1 KWVPRPSXBZNOHS-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methyl urea Chemical compound CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 8
- 230000036772 blood pressure Effects 0.000 description 7
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- MGJKQDOBUOMPEZ-UHFFFAOYSA-N N,N'-dimethylurea Chemical compound CNC(=O)NC MGJKQDOBUOMPEZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
- RZYVZALRKACWRX-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)-1,3-dimethyl-6-sulfanylidenepyrimidin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC(=S)N(C)C(=O)N1C RZYVZALRKACWRX-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 229960001866 silicon dioxide Drugs 0.000 description 5
- 238000010792 warming Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- BHSYONGONOKNAI-UHFFFAOYSA-N ethyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=C(OC)C(OC)=C1 BHSYONGONOKNAI-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 230000000304 vasodilatating effect Effects 0.000 description 4
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 3
- DCEGRFKPBZZMGE-UHFFFAOYSA-N 6-(3,4-dimethoxyphenyl)-3-methyl-4-sulfanylidene-1h-pyrimidin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC(=S)N(C)C(=O)N1 DCEGRFKPBZZMGE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 3
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 150000008065 acid anhydrides Chemical class 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000003973 alkyl amines Chemical class 0.000 description 3
- 230000003276 anti-hypertensive effect Effects 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- CHQUSPSYBGOASD-UHFFFAOYSA-N 1,3-dimethyl-4-sulfanylidene-6-(3,4,5-trimethoxyphenyl)pyrimidin-2-one Chemical compound COC1=C(OC)C(OC)=CC(C=2N(C(=O)N(C)C(=S)C=2)C)=C1 CHQUSPSYBGOASD-UHFFFAOYSA-N 0.000 description 2
- FNSAKXLEFPFZOM-UHFFFAOYSA-N 2,4,6-trimethoxyaniline Chemical compound COC1=CC(OC)=C(N)C(OC)=C1 FNSAKXLEFPFZOM-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
- KDDPNNXAZURUGP-UHFFFAOYSA-N 2-[2-(3,4-dichlorophenyl)-3-[2-(piperidin-3-ylamino)pyrimidin-4-yl]imidazol-4-yl]acetonitrile Chemical compound ClC=1C=C(C=CC=1Cl)C=1N(C(=CN=1)CC#N)C1=NC(=NC=C1)NC1CNCCC1 KDDPNNXAZURUGP-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- ANAWTBRBLCXKCQ-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)-1,3-diethyl-6-sulfanylidenepyrimidin-2-one Chemical compound S=C1N(CC)C(=O)N(CC)C(C=2C=C(OC)C(OC)=CC=2)=C1 ANAWTBRBLCXKCQ-UHFFFAOYSA-N 0.000 description 2
- ZNVXYGFZHASVGH-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)-1-methyl-3-propyl-6-sulfanylidenepyrimidin-2-one Chemical compound S=C1N(C)C(=O)N(CCC)C(C=2C=C(OC)C(OC)=CC=2)=C1 ZNVXYGFZHASVGH-UHFFFAOYSA-N 0.000 description 2
- OYGHXRNCHYRYRR-UHFFFAOYSA-N 6-(3,4-dimethoxyphenyl)-1-ethyl-3-methyl-4-(2,4,6-trimethylphenyl)iminopyrimidin-2-one Chemical compound CN1C(=O)N(CC)C(C=2C=C(OC)C(OC)=CC=2)=CC1=NC1=C(C)C=C(C)C=C1C OYGHXRNCHYRYRR-UHFFFAOYSA-N 0.000 description 2
- JBFXUEXTFAJUSA-UHFFFAOYSA-N 6-(3,4-dimethoxyphenyl)-3-methyl-1h-pyrimidine-2,4-dione Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC(=O)N(C)C(=O)N1 JBFXUEXTFAJUSA-UHFFFAOYSA-N 0.000 description 2
- VTGPBXIGZNZSBJ-UHFFFAOYSA-N 6-(3,4-dimethoxyphenyl)-3-methyl-2-propan-2-yloxypyrimidine-4-thione Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC(=S)N(C)C(OC(C)C)=N1 VTGPBXIGZNZSBJ-UHFFFAOYSA-N 0.000 description 2
- YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- VPGRYOFKCNULNK-ACXQXYJUSA-N Deoxycorticosterone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)C)[C@@]1(C)CC2 VPGRYOFKCNULNK-ACXQXYJUSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 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 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
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- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- NZWBIHXYURLIIA-UHFFFAOYSA-N methyl 2-(3,4-dimethoxyphenyl)-3-oxopropanoate Chemical compound COC(=O)C(C=O)C1=CC=C(OC)C(OC)=C1 NZWBIHXYURLIIA-UHFFFAOYSA-N 0.000 description 1
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- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
- GUOONOJYWQOJJP-DCMFLLSESA-N n-[(2s,3r)-3-hydroxy-1-phenyl-4-[[3-(trifluoromethoxy)phenyl]methylamino]butan-2-yl]-3-[methyl(methylsulfonyl)amino]-5-[(2r)-2-(4-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carbonyl]benzamide Chemical compound C1([C@H]2CCCN2C(=O)C=2C=C(C=C(C=2)N(C)S(C)(=O)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)[C@H](O)CNCC=2C=C(OC(F)(F)F)C=CC=2)=NC(C)=CS1 GUOONOJYWQOJJP-DCMFLLSESA-N 0.000 description 1
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- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 150000008512 pyrimidinediones Chemical class 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 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
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon 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
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8308290 | 1983-03-25 | ||
| GB838308290A GB8308290D0 (en) | 1983-03-25 | 1983-03-25 | Pyrimidinone derivatives |
| GB838315542A GB8315542D0 (en) | 1983-06-07 | 1983-06-07 | Pyrimidinone derivatives |
| GB8315542 | 1983-07-07 | ||
| GB8327859 | 1983-10-18 | ||
| GB838327859A GB8327859D0 (en) | 1983-10-18 | 1983-10-18 | Pyrimidine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1256107A true CA1256107A (en) | 1989-06-20 |
Family
ID=27262023
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000450076A Expired CA1256107A (en) | 1983-03-25 | 1984-03-21 | Pyrimidine derivatives, preparation thereof and use thereof |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US4612376A (instruction) |
| EP (1) | EP0123402B1 (instruction) |
| KR (1) | KR840008333A (instruction) |
| CA (1) | CA1256107A (instruction) |
| DE (1) | DE3473875D1 (instruction) |
| DK (1) | DK160492C (instruction) |
| ES (2) | ES8505972A1 (instruction) |
| FI (1) | FI841128A7 (instruction) |
| GR (1) | GR81758B (instruction) |
| HU (1) | HU195195B (instruction) |
| NO (1) | NO841168L (instruction) |
| PH (1) | PH22022A (instruction) |
| SU (2) | SU1349698A3 (instruction) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4612376A (en) * | 1983-03-25 | 1986-09-16 | Fujisawa Pharmaceutical Co., Ltd. | Substituted-3,4-dihydro-4-(2,4,6-trimethoxyphenylimino)-2(1H)-pyrimidones useful as cardiotonic, antihypertensive, cerebrovascular vasodilator and anti-platelet agent |
| US4598149A (en) * | 1984-03-02 | 1986-07-01 | Merck & Co., Inc. | 3-amino-2-hydroxypropyl of pyrimidin-4-one useful as antihypertensive, cardioprotective, antiarrythmic, and antianginal agents |
| US4649142A (en) * | 1984-06-25 | 1987-03-10 | Fujisawa Pharmaceutical Co., Ltd. | 3,4-dihydro-1,3-disubstituted-6-(substituted phenylimino)-2(1H)-pyrimidinone useful as cardiotonic agent and anti-allergic agent |
| US4708958A (en) * | 1986-09-24 | 1987-11-24 | G. D. Searle & Co. | 6-(imidazolyphenyl)-4-iminopyrimidinones useful as hypotensive agents |
| US5521315A (en) * | 1993-01-12 | 1996-05-28 | Cell Therapeutics, Inc. | Olefin substituted long chain compounds |
| IT1270122B (it) * | 1994-10-04 | 1997-04-28 | Ist Superiore Sanita | 6-benzil-4-ossopirimidine sostituite, processo per la loro preparazione e composizioni farmaceutiche che le contengono |
| CA2230516C (en) * | 1995-09-06 | 2008-11-18 | Kowa Co., Ltd. | Pyrimidine derivatives |
| US6244121B1 (en) * | 1998-03-06 | 2001-06-12 | Applied Materials, Inc. | Sensor device for non-intrusive diagnosis of a semiconductor processing system |
| ATE374766T1 (de) | 2003-01-14 | 2007-10-15 | Arena Pharm Inc | 1,2,3-trisubstituierte aryl- und heteroarylderivate als modulatoren des metabolismus zur vorbeugung und behandlung von metabolismus-bedingten krankheiten wie diabetes oder hyperglykämie |
| NZ544200A (en) | 2003-07-14 | 2009-07-31 | Arena Pharm Inc | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| DOP2006000009A (es) | 2005-01-13 | 2006-08-15 | Arena Pharm Inc | Procedimiento para preparar eteres de pirazolo [3,4-d] pirimidina |
| KR101452518B1 (ko) | 2005-08-22 | 2014-10-21 | 멜리어 파마슈티칼스 아이, 인코포레이티드 | Ｌｙｎ 키나제 활성의 조절 및 관련된 장애의 치료를 위한방법 및 제제 |
| CA2678813A1 (en) * | 2007-02-20 | 2008-08-28 | Melior Pharmaceuticals I, Inc. | Methods of identifying activators of lyn kinase |
| CN101668530A (zh) * | 2007-07-23 | 2010-03-10 | 梅利奥尔探索公司 | 激活irs-1和akt的方法 |
| US8552184B2 (en) * | 2008-07-03 | 2013-10-08 | Melior Pharmaceuticals I, Inc. | Compounds and methods for treating disorders related to glucose metabolism |
| EP2462123B1 (en) * | 2009-08-04 | 2013-10-02 | Merck Sharp & Dohme Corp. | 4,5,6-trisubstituted pyrimidine derivatives as factor ixa inhibitors |
| SG10201500639TA (en) | 2010-01-27 | 2015-03-30 | Arena Pharm Inc | Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof |
| US20130158055A1 (en) | 2010-05-28 | 2013-06-20 | Andrew G. Reaume | Prevention Of Pancreatic Beta Cell Degeneration |
| BR112013008100A2 (pt) | 2010-09-22 | 2016-08-09 | Arena Pharm Inc | "moduladores do receptor de gpr19 e o tratamento de distúrbios relacionados a eles." |
| US10183949B2 (en) | 2014-08-29 | 2019-01-22 | The University Of Tokyo | Pyrimidinone derivative having autotaxin-inhibitory activity |
| EP3187492A4 (en) * | 2014-08-29 | 2018-05-09 | The University of Tokyo | Pyrimidinone derivative having autotaxin-inhibitory activity |
| HUE069888T2 (hu) | 2015-01-06 | 2025-04-28 | Arena Pharm Inc | Vegyületek az S1P1 receptorral összefüggõ állapotok kezelésében történõ alkalmazásra |
| KR102883123B1 (ko) | 2015-06-22 | 2025-11-10 | 아레나 파마슈티칼스, 인크. | Ｓ1ｐ1 수용체-관련 장애에서의 사용을 위한 (ｒ)-2-(7-(4-시클로펜틸-3-(트리플루오로메틸)벤질옥시)-1,2,3,4-테트라히드로시클로-펜타[ｂ]인돌-3-일)아세트산 (화합물 1)의 결정성 ｌ-아르기닌 염 |
| MA47504A (fr) | 2017-02-16 | 2019-12-25 | Arena Pharm Inc | Composés et méthodes de traitement de l'angiocholite biliaire primitive |
| KR102634575B1 (ko) | 2017-04-10 | 2024-02-06 | 멜리어 파마슈티칼스 아이, 인코포레이티드 | 지방세포의 처리 |
| CN112601516A (zh) | 2018-06-06 | 2021-04-02 | 艾尼纳制药公司 | 治疗与s1p1受体相关的病况的方法 |
| CN109053589A (zh) * | 2018-09-30 | 2018-12-21 | 浙江师范大学 | 4-亚胺基四氢嘧啶-2-酮类化合物的制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1296371A (instruction) * | 1969-02-26 | 1972-11-15 | ||
| AU1108070A (en) * | 1969-03-06 | 1971-08-12 | Imperial Chemical Industries Limited | Pyrimidine derivatives |
| GB1336138A (en) * | 1969-12-10 | 1973-11-07 | Ici Ltd | Process for the production of pyrimidine derivatives |
| US3923807A (en) * | 1973-09-10 | 1975-12-02 | Takeda Chemical Industries Ltd | 6-Aminouracil derivatives |
| US4208366A (en) * | 1978-10-31 | 1980-06-17 | E. I. Du Pont De Nemours And Company | Process for preparing a nonwoven web |
| DE2847693A1 (de) * | 1978-11-03 | 1980-05-22 | Hoechst Ag | Verfahren zur herstellung von pyrimido-(6,1-a)-isochinolin-2-onen |
| US4612376A (en) * | 1983-03-25 | 1986-09-16 | Fujisawa Pharmaceutical Co., Ltd. | Substituted-3,4-dihydro-4-(2,4,6-trimethoxyphenylimino)-2(1H)-pyrimidones useful as cardiotonic, antihypertensive, cerebrovascular vasodilator and anti-platelet agent |
-
1984
- 1984-03-12 US US06/588,902 patent/US4612376A/en not_active Expired - Fee Related
- 1984-03-14 GR GR74104A patent/GR81758B/el unknown
- 1984-03-14 DE DE8484301741T patent/DE3473875D1/de not_active Expired
- 1984-03-14 EP EP84301741A patent/EP0123402B1/en not_active Expired
- 1984-03-14 PH PH30400A patent/PH22022A/en unknown
- 1984-03-20 KR KR1019840001414A patent/KR840008333A/ko not_active Ceased
- 1984-03-21 CA CA000450076A patent/CA1256107A/en not_active Expired
- 1984-03-21 FI FI841128A patent/FI841128A7/fi not_active Application Discontinuation
- 1984-03-23 HU HU841170A patent/HU195195B/hu not_active IP Right Cessation
- 1984-03-23 ES ES530916A patent/ES8505972A1/es not_active Expired
- 1984-03-23 SU SU843718401A patent/SU1349698A3/ru active
- 1984-03-23 DK DK166884A patent/DK160492C/da active IP Right Grant
- 1984-03-23 NO NO841168A patent/NO841168L/no unknown
- 1984-11-30 ES ES538190A patent/ES8601922A1/es not_active Expired
-
1985
- 1985-03-28 SU SU853892541A patent/SU1436872A3/ru active
-
1986
- 1986-06-05 US US06/870,826 patent/US4746664A/en not_active Expired - Fee Related
-
1988
- 1988-03-25 US US07/173,584 patent/US4824851A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES530916A0 (es) | 1985-06-16 |
| EP0123402A3 (en) | 1985-09-18 |
| DK160492C (da) | 1991-08-26 |
| PH22022A (en) | 1988-05-13 |
| GR81758B (instruction) | 1984-12-12 |
| DK160492B (da) | 1991-03-18 |
| HU195195B (en) | 1988-04-28 |
| SU1349698A3 (ru) | 1987-10-30 |
| US4824851A (en) | 1989-04-25 |
| EP0123402B1 (en) | 1988-09-07 |
| EP0123402A2 (en) | 1984-10-31 |
| FI841128A0 (fi) | 1984-03-21 |
| FI841128A7 (fi) | 1984-09-26 |
| NO841168L (no) | 1984-09-26 |
| US4746664A (en) | 1988-05-24 |
| US4612376A (en) | 1986-09-16 |
| ES8505972A1 (es) | 1985-06-16 |
| KR840008333A (ko) | 1984-12-14 |
| DK166884D0 (da) | 1984-03-23 |
| DK166884A (da) | 1984-09-26 |
| DE3473875D1 (en) | 1988-10-13 |
| ES538190A0 (es) | 1985-11-01 |
| ES8601922A1 (es) | 1985-11-01 |
| SU1436872A3 (ru) | 1988-11-07 |
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