HRP930793A2 - Pyrimidine derivatives - Google Patents

Pyrimidine derivatives Download PDF

Info

Publication number: HRP930793A2
Authority: HR; Croatia
Prior art keywords: alkyl; methyl; formula; phenyl; ethyl
Prior art date: 1989-04-21

Application number

HRP-799/90A

Other languages

English (en)

Croatian (hr)

Inventor

Rodney Brian Hargreaves

Paul William Marshall

Bernard Joseph Mcloughlin

Stuart Dennett Mills

Original Assignee

Ici Plc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1989-04-21

Filing date

1993-04-06

Publication date

1996-08-31

1989-04-21 Priority claimed from GB898909054A external-priority patent/GB8909054D0/en

1989-05-08 Priority claimed from GB898910548A external-priority patent/GB8910548D0/en

1993-04-06 Application filed by Ici Plc filed Critical Ici Plc

1996-08-31 Publication of HRP930793A2 publication Critical patent/HRP930793A2/hr

Links

150000003230 pyrimidines Chemical class 0.000 title claims description 18
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
-1 pyrrolidino, piperidino Chemical group 0.000 claims abstract description 119
150000001875 compounds Chemical class 0.000 claims abstract description 108
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 91
125000000217 alkyl group Chemical group 0.000 claims abstract description 83
238000000034 method Methods 0.000 claims abstract description 76
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 43
239000001257 hydrogen Substances 0.000 claims abstract description 42
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 28
125000002947 alkylene group Chemical group 0.000 claims abstract description 21
125000003342 alkenyl group Chemical group 0.000 claims abstract description 20
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 20
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 19
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 19
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 19
150000001450 anions Chemical class 0.000 claims abstract description 17
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 17
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 10
125000005647 linker group Chemical group 0.000 claims abstract description 10
125000004450 alkenylene group Chemical group 0.000 claims abstract description 9
125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
230000008569 process Effects 0.000 claims abstract description 5
125000002541 furyl group Chemical group 0.000 claims abstract description 4
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 4
125000001544 thienyl group Chemical group 0.000 claims abstract description 4
239000004480 active ingredient Substances 0.000 claims abstract description 3
238000004519 manufacturing process Methods 0.000 claims abstract description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 100
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 18
239000000460 chlorine Substances 0.000 claims description 16
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 15
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 15
238000002360 preparation method Methods 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 14
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 12
239000002168 alkylating agent Substances 0.000 claims description 11
229940100198 alkylating agent Drugs 0.000 claims description 11
229910052736 halogen Inorganic materials 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 11
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 9
150000001412 amines Chemical class 0.000 claims description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
229920005989 resin Polymers 0.000 claims description 8
239000011347 resin Substances 0.000 claims description 8
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 7
229910052794 bromium Inorganic materials 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
239000003085 diluting agent Substances 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
150000005005 aminopyrimidines Chemical class 0.000 claims description 6
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
125000006022 2-methyl-2-propenyl group Chemical group 0.000 claims description 5
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 claims description 5
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 claims description 5
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 5
229910052702 rhenium Inorganic materials 0.000 claims description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
239000005977 Ethylene Substances 0.000 claims description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
239000000908 ammonium hydroxide Substances 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 4
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
125000001041 indolyl group Chemical group 0.000 claims description 4
229910052740 iodine Inorganic materials 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 4
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
125000004414 alkyl thio group Chemical group 0.000 claims description 3
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 3
NTBIYBAYFBNTCD-UHFFFAOYSA-N dibenzoyl 2,3-dihydroxybutanedioate Chemical class C=1C=CC=CC=1C(=O)OC(=O)C(O)C(O)C(=O)OC(=O)C1=CC=CC=C1 NTBIYBAYFBNTCD-UHFFFAOYSA-N 0.000 claims description 3
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 3
150000004820 halides Chemical class 0.000 claims description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 2
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
229910019142 PO4 Inorganic materials 0.000 claims description 2
125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
229910021529 ammonia Inorganic materials 0.000 claims description 2
125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000005265 dialkylamine group Chemical group 0.000 claims description 2
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 2
125000006125 ethylsulfonyl group Chemical group 0.000 claims description 2
230000007717 exclusion Effects 0.000 claims description 2
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
238000005342 ion exchange Methods 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
239000000825 pharmaceutical preparation Substances 0.000 claims description 2
125000001453 quaternary ammonium group Chemical group 0.000 claims description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
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 3
DUIMWXDLDBNUFD-UHFFFAOYSA-N 4-pyrimidin-2-ylmorpholine Chemical class C1COCCN1C1=NC=CC=N1 DUIMWXDLDBNUFD-UHFFFAOYSA-N 0.000 claims 1
PUBBXRHYTJEALC-UHFFFAOYSA-O 6-(3-ethyl-2,3-dihydroindol-1-yl)-n,2,3-trimethylpyrimidin-3-ium-4-amine Chemical compound C12=CC=CC=C2C(CC)CN1C1=CC(NC)=[N+](C)C(C)=N1 PUBBXRHYTJEALC-UHFFFAOYSA-O 0.000 claims 1
HRUMCRUAEHLVQY-UHFFFAOYSA-N CC(N(C)C(NC)=C1)N=C1N1C2=CC=CC=C2C(C)=C1 Chemical compound CC(N(C)C(NC)=C1)N=C1N1C2=CC=CC=C2C(C)=C1 HRUMCRUAEHLVQY-UHFFFAOYSA-N 0.000 claims 1
YRGRLAUVURHEQH-UHFFFAOYSA-N CCC(C1=CC=CC=C11)=CN1C1=NC(C)N(C)C(NC)=C1 Chemical compound CCC(C1=CC=CC=C11)=CN1C1=NC(C)N(C)C(NC)=C1 YRGRLAUVURHEQH-UHFFFAOYSA-N 0.000 claims 1
JYHPMLYLJBLDSG-UHFFFAOYSA-N CCC(N(C)C(NC)=C1)N=C1N1C2=CC=CC=C2C(CC)=C1 Chemical compound CCC(N(C)C(NC)=C1)N=C1N1C2=CC=CC=C2C(CC)=C1 JYHPMLYLJBLDSG-UHFFFAOYSA-N 0.000 claims 1
JYLLWHNQWQASMT-UHFFFAOYSA-N CN1C(N=C(C=C1NC)N1C=CC2=CC=CC=C12)C Chemical compound CN1C(N=C(C=C1NC)N1C=CC2=CC=CC=C12)C JYLLWHNQWQASMT-UHFFFAOYSA-N 0.000 claims 1
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 1
150000001242 acetic acid derivatives Chemical class 0.000 claims 1
150000001558 benzoic acid derivatives Chemical class 0.000 claims 1
150000004648 butanoic acid derivatives Chemical class 0.000 claims 1
150000001768 cations Chemical class 0.000 claims 1
150000001860 citric acid derivatives Chemical class 0.000 claims 1
IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 claims 1
239000002184 metal Substances 0.000 claims 1
229910052751 metal Inorganic materials 0.000 claims 1
125000005528 methosulfate group Chemical group 0.000 claims 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
150000002823 nitrates Chemical class 0.000 claims 1
235000021317 phosphate Nutrition 0.000 claims 1
150000003013 phosphoric acid derivatives Chemical class 0.000 claims 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
150000003467 sulfuric acid derivatives Chemical class 0.000 claims 1
150000003892 tartrate salts Chemical class 0.000 claims 1
210000000748 cardiovascular system Anatomy 0.000 abstract description 7
210000001013 sinoatrial node Anatomy 0.000 abstract description 6
230000009286 beneficial effect Effects 0.000 abstract description 5
125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract description 4
125000004183 alkoxy alkyl group Chemical group 0.000 abstract description 2
125000005702 oxyalkylene group Chemical group 0.000 abstract description 2
239000008194 pharmaceutical composition Substances 0.000 abstract description 2
125000003884 phenylalkyl group Chemical group 0.000 abstract 3
JASUSRFZNVUXRL-UHFFFAOYSA-N pyrimidin-1-ium-1-amine Chemical class N[N+]1=CC=CN=C1 JASUSRFZNVUXRL-UHFFFAOYSA-N 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 86
239000007787 solid Substances 0.000 description 86
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
238000002844 melting Methods 0.000 description 73
230000008018 melting Effects 0.000 description 73
239000000203 mixture Substances 0.000 description 69
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 61
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 46
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 42
239000000243 solution Substances 0.000 description 42
229910001868 water Inorganic materials 0.000 description 42
239000000126 substance Substances 0.000 description 39
239000002904 solvent Substances 0.000 description 38
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 30
238000001914 filtration Methods 0.000 description 29
238000006243 chemical reaction Methods 0.000 description 25
238000004452 microanalysis Methods 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
239000007858 starting material Substances 0.000 description 23
OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 description 21
235000019439 ethyl acetate Nutrition 0.000 description 18
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 18
238000005481 NMR spectroscopy Methods 0.000 description 17
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
125000003118 aryl group Chemical group 0.000 description 16
238000010992 reflux Methods 0.000 description 16
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
230000000694 effects Effects 0.000 description 14
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
239000000284 extract Substances 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
238000001953 recrystallisation Methods 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
238000001704 evaporation Methods 0.000 description 10
230000008020 evaporation Effects 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
238000012360 testing method Methods 0.000 description 8
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical class ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 7
230000000059 bradycardiac effect Effects 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
239000003480 eluent Substances 0.000 description 7
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 6
150000005698 chloropyrimidines Chemical class 0.000 description 6
238000000354 decomposition reaction Methods 0.000 description 6
230000036961 partial effect Effects 0.000 description 6
238000000746 purification Methods 0.000 description 6
XNVNMEQYZOCXNK-UHFFFAOYSA-N 4-chloro-n,6-dimethylpyrimidin-2-amine Chemical compound CNC1=NC(C)=CC(Cl)=N1 XNVNMEQYZOCXNK-UHFFFAOYSA-N 0.000 description 5
239000012300 argon atmosphere Substances 0.000 description 5
230000008901 benefit Effects 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
238000005191 phase separation Methods 0.000 description 5
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IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 description 1
OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical class NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
ZSIALBZCWCLSOG-UHFFFAOYSA-N pyrimidine;hydroiodide Chemical compound I.C1=CN=CN=C1 ZSIALBZCWCLSOG-UHFFFAOYSA-N 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000007921 spray Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
230000006794 tachycardia Effects 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
229960000103 thrombolytic agent Drugs 0.000 description 1
DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
231100000399 thyrotoxic Toxicity 0.000 description 1
230000001897 thyrotoxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
238000007738 vacuum evaporation Methods 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
238000005406 washing Methods 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
- 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
- A61P9/06—Antiarrhythmics
- 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
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

HRP-799/90A 1989-04-21 1993-04-06 Pyrimidine derivatives HRP930793A2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB898909054A GB8909054D0 (en)	1989-04-21	1989-04-21	Amino heterocycles
GB898910548A GB8910548D0 (en)	1989-05-08	1989-05-08	Heterocyclic compounds
YU00799/90A YU79990A (en)	1989-04-21	1990-04-19	Pyrimidine derivatives

Publications (1)

Publication Number	Publication Date
HRP930793A2 true HRP930793A2 (en)	1996-08-31

Family

ID=26295250

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HRP-799/90A HRP930793A2 (en)	1989-04-21	1993-04-06	Pyrimidine derivatives

Country Status (29)

Country	Link
US (1)	US5223505A (fr)
EP (1)	EP0422178B1 (fr)
JP (1)	JP2528218B2 (fr)
KR (1)	KR920700203A (fr)
CN (1)	CN1024793C (fr)
AT (1)	ATE112561T1 (fr)
AU (1)	AU635260B2 (fr)
BG (1)	BG93508A (fr)
CA (1)	CA2014457C (fr)
DE (1)	DE69013112T2 (fr)
DK (1)	DK0422178T3 (fr)
ES (1)	ES2064727T3 (fr)
FI (1)	FI95377C (fr)
GB (1)	GB2230527B (fr)
GR (1)	GR1000371B (fr)
HR (1)	HRP930793A2 (fr)
HU (1)	HU209586B (fr)
IE (1)	IE63502B1 (fr)
IL (1)	IL94062A (fr)
MW (1)	MW9090A1 (fr)
MY (1)	MY105637A (fr)
NO (1)	NO177054C (fr)
NZ (1)	NZ233292A (fr)
PL (2)	PL165917B1 (fr)
PT (1)	PT93823B (fr)
RU (1)	RU2108329C1 (fr)
SI (1)	SI9010799A (fr)
WO (1)	WO1990012790A1 (fr)
YU (1)	YU79990A (fr)

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DE60025837T2 (de)	1999-09-24	2006-11-02	Janssen Pharmaceutica N.V.	Antivirale feste dispersionen
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BR0313059B8 (pt)	2002-07-29	2021-07-27	Rigel Pharmaceuticals	composto, e, composição farmacêutica
CA2518465A1 (fr)	2003-03-25	2004-10-14	Takeda San Diego, Inc.	Inhibiteurs de dipeptidyle peptidase
US8309562B2 (en)	2003-07-03	2012-11-13	Myrexis, Inc.	Compounds and therapeutical use thereof
WO2005003100A2 (fr) *	2003-07-03	2005-01-13	Myriad Genetics, Inc.	Composes et leur utilisation therapeutique
WO2006074147A2 (fr)	2005-01-03	2006-07-13	Myriad Genetics, Inc.	Composes et utilisation therapeutique associee
CN102358738A (zh)	2003-07-30	2012-02-22	里格尔药品股份有限公司	2,4-嘧啶二胺化合物及其预防和治疗自体免疫疾病的用途
KR20060041309A (ko)	2003-08-13	2006-05-11	다케다 야쿠힌 고교 가부시키가이샤	４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도
JP2007505121A (ja)	2003-09-08	2007-03-08	武田薬品工業株式会社	ジペプチジルぺプチダーゼ阻害剤
EA013427B1 (ru)	2004-03-15	2010-04-30	Такеда Фармасьютикал Компани Лимитед	Ингибиторы дипептидилпептидазы
JP5095409B2 (ja)	2004-11-24	2012-12-12	ライジェルファーマシューティカルズ，インコーポレイテッド	スピロ２，４−ピリミジンジアミン化合物およびその使用
EP1828192B1 (fr)	2004-12-21	2014-12-03	Takeda Pharmaceutical Company Limited	Inhibiteurs de dipeptidyle peptidase
US8258145B2 (en)	2005-01-03	2012-09-04	Myrexis, Inc.	Method of treating brain cancer
JP4801096B2 (ja)	2005-01-19	2011-10-26	ライジェルファーマシューティカルズ，インコーポレイテッド	２，４−ピリミジンジアミン化合物のプロドラッグおよびそれらの使用
US20060270694A1 (en) *	2005-05-03	2006-11-30	Rigel Pharmaceuticals, Inc.	JAK kinase inhibitors and their uses
ES2437202T3 (es)	2005-05-26	2014-01-09	Janssen R&D Ireland	Procedimiento para preparar 4-[(1,6-dihidro-6-oxo-2-pirimidinil)-amino]benzonitrilo
AU2006290205B2 (en)	2005-09-14	2012-12-13	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors for treating diabetes
CA2622642C (fr)	2005-09-16	2013-12-31	Takeda Pharmaceutical Company Limited	Inhibiteurs de dipeptidylpeptidase
US20090221610A1 (en) *	2006-01-31	2009-09-03	Yale University	Compositions and Methods for Treating Cognitive Disorders
US8324383B2 (en)	2006-09-13	2012-12-04	Takeda Pharmaceutical Company Limited	Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
TW200838536A (en)	2006-11-29	2008-10-01	Takeda Pharmaceutical	Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
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1990
- 1990-04-06 IE IE125890A patent/IE63502B1/en not_active IP Right Cessation
- 1990-04-09 GB GB9007964A patent/GB2230527B/en not_active Expired - Fee Related
- 1990-04-11 NZ NZ233292A patent/NZ233292A/en unknown
- 1990-04-11 IL IL9406290A patent/IL94062A/en not_active IP Right Cessation
- 1990-04-12 CA CA002014457A patent/CA2014457C/fr not_active Expired - Fee Related
- 1990-04-19 RU SU4894489A patent/RU2108329C1/ru active
- 1990-04-19 DK DK90906289.5T patent/DK0422178T3/da active
- 1990-04-19 WO PCT/GB1990/000595 patent/WO1990012790A1/fr not_active Ceased
- 1990-04-19 JP JP2506034A patent/JP2528218B2/ja not_active Expired - Lifetime
- 1990-04-19 ES ES90906289T patent/ES2064727T3/es not_active Expired - Lifetime
- 1990-04-19 HU HU903555A patent/HU209586B/hu not_active IP Right Cessation
- 1990-04-19 AT AT90906289T patent/ATE112561T1/de not_active IP Right Cessation
- 1990-04-19 EP EP90906289A patent/EP0422178B1/fr not_active Expired - Lifetime
- 1990-04-19 AU AU54354/90A patent/AU635260B2/en not_active Ceased
- 1990-04-19 KR KR1019900702652A patent/KR920700203A/ko not_active Ceased
- 1990-04-19 YU YU00799/90A patent/YU79990A/xx unknown
- 1990-04-19 DE DE69013112T patent/DE69013112T2/de not_active Expired - Fee Related
- 1990-04-20 PL PL90301231A patent/PL165917B1/pl unknown
- 1990-04-20 SI SI9010799A patent/SI9010799A/sl unknown
- 1990-04-20 PT PT93823A patent/PT93823B/pt not_active IP Right Cessation
- 1990-04-20 PL PL90284871A patent/PL165502B1/pl unknown
- 1990-04-20 US US07/513,304 patent/US5223505A/en not_active Expired - Fee Related
- 1990-04-21 CN CN90103931A patent/CN1024793C/zh not_active Expired - Fee Related
- 1990-04-21 MY MYPI90000670A patent/MY105637A/en unknown
- 1990-04-23 GR GR900100304A patent/GR1000371B/el not_active IP Right Cessation
- 1990-12-06 MW MW90/90A patent/MW9090A1/xx unknown
- 1990-12-20 FI FI906307A patent/FI95377C/fi not_active IP Right Cessation
- 1990-12-20 NO NO905519A patent/NO177054C/no not_active IP Right Cessation
- 1990-12-21 BG BG093508A patent/BG93508A/bg unknown
1993
- 1993-04-06 HR HRP-799/90A patent/HRP930793A2/hr not_active Application Discontinuation

Also Published As

Publication number	Publication date
NO905519D0 (no)	1990-12-20
ES2064727T3 (es)	1995-02-01
US5223505A (en)	1993-06-29
PL165502B1 (pl)	1994-12-30
MW9090A1 (en)	1991-11-13
DE69013112D1 (de)	1994-11-10
ATE112561T1 (de)	1994-10-15
CA2014457C (fr)	1999-09-28
DK0422178T3 (da)	1994-12-19
GR900100304A (en)	1991-09-27
DE69013112T2 (de)	1995-01-26
NO177054C (no)	1995-07-12
PL165917B1 (pl)	1995-03-31
FI95377C (fi)	1996-01-25
JP2528218B2 (ja)	1996-08-28
BG93508A (bg)	1993-12-24
GR1000371B (el)	1992-06-30
JPH03505741A (ja)	1991-12-12
FI95377B (fi)	1995-10-13
FI906307A0 (fi)	1990-12-20
HU209586B (en)	1994-08-29
CN1024793C (zh)	1994-06-01
NO177054B (no)	1995-04-03
KR920700203A (ko)	1992-02-19
RU2108329C1 (ru)	1998-04-10
HUT56080A (en)	1991-07-29
EP0422178A1 (fr)	1991-04-17
IL94062A0 (en)	1991-01-31
AU635260B2 (en)	1993-03-18
WO1990012790A1 (fr)	1990-11-01
EP0422178B1 (fr)	1994-10-05
MY105637A (en)	1994-11-30
IE901258L (en)	1990-10-21
HU903555D0 (en)	1991-05-28
YU79990A (en)	1991-10-31
SI9010799A (en)	1995-08-31
CN1047080A (zh)	1990-11-21
GB2230527B (en)	1993-05-05
NO905519L (no)	1991-02-20
CA2014457A1 (fr)	1990-10-21
IL94062A (en)	1995-11-27
GB9007964D0 (en)	1990-06-06
PT93823B (pt)	1996-09-30
NZ233292A (en)	1992-05-26
PT93823A (pt)	1990-11-20
AU5435490A (en)	1990-11-16
GB2230527A (en)	1990-10-24
IE63502B1 (en)	1995-05-03

Legal Events

Date	Code	Title	Description
1996-08-31	A1OB	Publication of a patent application
1998-04-07	ODBC	Application rejected

Publication	Publication Date	Title
AU635260B2 (en)	1993-03-18	Aminopyrimidinum salts sino-atrial node modulated effects
EP0168262A2 (fr)	1986-01-15	Dérivés de pyrimidine, procédés pour leur préparation et leur utilisation
EP0123402A2 (fr)	1984-10-31	Dérivés de pyrimidine, leur préparation et leur utilisation
US4782055A (en)	1988-11-01	Imidazopyridine compounds useful in the treatment of ulcers
Campbell et al.	1987	2, 4-Diamino-6, 7-dimethoxyquinazolines. 3. 2-(4-heterocyclylpiperazin-1-yl) derivatives as. alpha. 1-adrenoceptor antagonists and antihypertensive agents
US5328910A (en)	1994-07-12	Sino-atrial node modulating pyrrolopyrimidines
US5252567A (en)	1993-10-12	Diazine derivatives
US5332737A (en)	1994-07-26	Amino-1,3,5-triazines and their anhydrobase derivatives as agents for cardiovascular system
CN117229262A (zh)	2023-12-15	多芳香环egfr抑制剂的制备及其应用
DD297406A5 (de)	1992-01-09	Pyrimidinderivate
PL165715B1 (pl)	1995-01-31	Sposób wytwarzania nowych pochodnych am inopirymidyny PL