NO312133B1 - 4-amino-2-ureido-pyrimidin-5-karboksylsyreamider, fremgangsmåter for deres fremstilling, legemidler inneholdendedisse forbindelsene og deres anvendelse - Google Patents

4-amino-2-ureido-pyrimidin-5-karboksylsyreamider, fremgangsmåter for deres fremstilling, legemidler inneholdendedisse forbindelsene og deres anvendelse Download PDF

Info

Publication number: NO312133B1
Authority: NO; Norway
Prior art keywords: alkyl; formula; fluorine; stands; compound
Prior art date: 1996-06-24

Application number

NO19972942A

Other languages

English (en)

Norwegian (no)

Other versions

NO972942L (no

NO972942D0 (no

Inventor

Gerhard Rackur

Hans Georg Boeger

Norbert Krass

Axel Hoffmann

Michael Leineweber

Original Assignee

Hoechst Ag

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.)

1996-06-24

Filing date

1997-06-23

Publication date

2002-03-25

1997-06-23 Application filed by Hoechst Ag filed Critical Hoechst Ag

1997-06-23 Publication of NO972942D0 publication Critical patent/NO972942D0/no

1997-12-29 Publication of NO972942L publication Critical patent/NO972942L/no

2002-03-25 Publication of NO312133B1 publication Critical patent/NO312133B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 79
238000000034 method Methods 0.000 title claims description 41
238000002360 preparation method Methods 0.000 title claims description 25
SHGZREYDEWHPDB-UHFFFAOYSA-N 4-amino-2-(carbamoylamino)pyrimidine-5-carboxamide Chemical class NC(=O)NC1=NC=C(C(N)=O)C(N)=N1 SHGZREYDEWHPDB-UHFFFAOYSA-N 0.000 title claims description 3
239000003814 drug Substances 0.000 title description 7
229940079593 drug Drugs 0.000 title description 5
229910052731 fluorine Inorganic materials 0.000 claims abstract description 34
150000003839 salts Chemical class 0.000 claims abstract description 22
229910052801 chlorine Inorganic materials 0.000 claims abstract description 17
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
125000000217 alkyl group Chemical group 0.000 claims abstract description 15
229910052794 bromium Inorganic materials 0.000 claims abstract description 11
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 10
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 33
239000011737 fluorine Substances 0.000 claims description 33
239000000460 chlorine Substances 0.000 claims description 20
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 16
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
-1 2,2,3,3,3-pentafluoropropyl Chemical group 0.000 claims description 14
239000002904 solvent Substances 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 11
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
PLYIXDXAACZULO-UHFFFAOYSA-N 2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-4-[(1-methylpyrrolidin-2-ylidene)amino]pyrimidine-5-carboxylic acid Chemical compound CN1CCCC1=NC1=NC(N2C(NC(C)(C)C2)=O)=NC=C1C(O)=O PLYIXDXAACZULO-UHFFFAOYSA-N 0.000 claims description 7
208000017170 Lipid metabolism disease Diseases 0.000 claims description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 claims description 4
LRAFTRZPKUWQPO-UHFFFAOYSA-N ethyl 2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-4-[(1-methylpyrrolidin-2-ylidene)amino]pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(N2C(NC(C)(C)C2)=O)N=C1N=C1CCCN1C LRAFTRZPKUWQPO-UHFFFAOYSA-N 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
UEWDJCZJEIBPKX-UHFFFAOYSA-N 2,2-diethoxy-1-methylpyrrolidine Chemical compound CCOC1(OCC)CCCN1C UEWDJCZJEIBPKX-UHFFFAOYSA-N 0.000 claims description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 3
208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 3
235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
FVSXVUBUAFAQHO-UHFFFAOYSA-N C1C(C)(C)NC(=O)N1C1(C(=O)OCC)NC=CC(N)=N1 Chemical compound C1C(C)(C)NC(=O)N1C1(C(=O)OCC)NC=CC(N)=N1 FVSXVUBUAFAQHO-UHFFFAOYSA-N 0.000 claims description 2
230000001225 therapeutic effect Effects 0.000 claims description 2
229940126601 medicinal product Drugs 0.000 claims 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 1
NKTWBSSRNCDNCD-UHFFFAOYSA-N 4-amino-2-(2-oxoimidazolidin-1-yl)pyrimidine-5-carboxamide Chemical class N1=C(N)C(C(=O)N)=CN=C1N1C(=O)NCC1 NKTWBSSRNCDNCD-UHFFFAOYSA-N 0.000 abstract 1
125000003545 alkoxy group Chemical group 0.000 abstract 1
125000004414 alkyl thio group Chemical group 0.000 abstract 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
QNHJNFAMXXEFIU-UHFFFAOYSA-N 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxylic acid Chemical compound O=C1NC(C)(C)CN1C1=NC=C(C(O)=O)C(N)=N1 QNHJNFAMXXEFIU-UHFFFAOYSA-N 0.000 description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
238000005160 1H NMR spectroscopy Methods 0.000 description 22
239000000243 solution Substances 0.000 description 20
108020004999 messenger RNA Proteins 0.000 description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
239000000203 mixture Substances 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
102000000853 LDL receptors Human genes 0.000 description 12
108010001831 LDL receptors Proteins 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000013543 active substance Substances 0.000 description 11
238000002844 melting Methods 0.000 description 11
230000008018 melting Effects 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
210000004185 liver Anatomy 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
238000005481 NMR spectroscopy Methods 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
238000011534 incubation Methods 0.000 description 9
238000003756 stirring Methods 0.000 description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
150000001408 amides Chemical class 0.000 description 8
235000019439 ethyl acetate Nutrition 0.000 description 8
210000003494 hepatocyte Anatomy 0.000 description 8
239000000825 pharmaceutical preparation Substances 0.000 description 8
239000012071 phase Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
239000013078 crystal Substances 0.000 description 7
238000000354 decomposition reaction Methods 0.000 description 7
230000004060 metabolic process Effects 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
239000003480 eluent Substances 0.000 description 6
239000002585 base Substances 0.000 description 5
239000000969 carrier Substances 0.000 description 5
239000002609 medium Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
238000010561 standard procedure Methods 0.000 description 5
230000000638 stimulation Effects 0.000 description 5
239000000126 substance Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
238000001816 cooling Methods 0.000 description 4
DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-UHFFFAOYSA-N 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
238000000746 purification Methods 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
239000007787 solid Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
239000003826 tablet Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
239000012043 crude product Substances 0.000 description 3
239000001963 growth medium Substances 0.000 description 3
238000009396 hybridization Methods 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
239000000523 sample Substances 0.000 description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
GEQZTCMVWVDEDF-UHFFFAOYSA-N 2-cyanoacetyl chloride Chemical compound ClC(=O)CC#N GEQZTCMVWVDEDF-UHFFFAOYSA-N 0.000 description 2
IXPCHRDFJPINFB-UHFFFAOYSA-N 4,4-dimethyl-2-oxoimidazolidine-1-carboximidamide Chemical compound CC1(C)CN(C(N)=N)C(=O)N1 IXPCHRDFJPINFB-UHFFFAOYSA-N 0.000 description 2
CANCNNXFBGDUHY-UHFFFAOYSA-N 4-amino-2-(carbamoylamino)pyrimidine-5-carboxylic acid Chemical class NC(=O)NC1=NC=C(C(O)=O)C(N)=N1 CANCNNXFBGDUHY-UHFFFAOYSA-N 0.000 description 2
SVOQOFSQLVVHKQ-UHFFFAOYSA-N 6-oxo-1h-pyrimidine-5-carbonitrile Chemical class O=C1NC=NC=C1C#N SVOQOFSQLVVHKQ-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
238000000636 Northern blotting Methods 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
230000020335 dealkylation Effects 0.000 description 2
238000006900 dealkylation reaction Methods 0.000 description 2
238000001514 detection method Methods 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
239000008298 dragée Substances 0.000 description 2
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LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical class Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 2
HXGNOMQPMBZQOT-UHFFFAOYSA-N ethyl 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxylate Chemical compound N1=C(N)C(C(=O)OCC)=CN=C1N1C(=O)NC(C)(C)C1 HXGNOMQPMBZQOT-UHFFFAOYSA-N 0.000 description 2
230000007717 exclusion Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
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NPFJOSKCSJJZPP-UHFFFAOYSA-N 4-amino-2-(2-oxoimidazolidin-1-yl)pyrimidine-5-carboxylic acid Chemical class C1=C(C(O)=O)C(N)=NC(N2C(NCC2)=O)=N1 NPFJOSKCSJJZPP-UHFFFAOYSA-N 0.000 description 1
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BIIQMYQNKUEXJT-UHFFFAOYSA-N 4-amino-2-(carbamoylamino)-n-phenylpyrimidine-5-carboxamide Chemical group NC1=NC(NC(=O)N)=NC=C1C(=O)NC1=CC=CC=C1 BIIQMYQNKUEXJT-UHFFFAOYSA-N 0.000 description 1
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GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
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PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical class NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- 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
- C07D403/14—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 three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Obesity (AREA)
Diabetes (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Hematology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

NO19972942A 1996-06-24 1997-06-23 4-amino-2-ureido-pyrimidin-5-karboksylsyreamider, fremgangsmåter for deres fremstilling, legemidler inneholdendedisse forbindelsene og deres anvendelse NO312133B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19625088A DE19625088A1 (de)	1996-06-24	1996-06-24	4-Amino-2-ureido-pyrimidin-5-carbonsäureamide, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung

Publications (3)

Publication Number	Publication Date
NO972942D0 NO972942D0 (no)	1997-06-23
NO972942L NO972942L (no)	1997-12-29
NO312133B1 true NO312133B1 (no)	2002-03-25

Family

ID=7797761

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19972942A NO312133B1 (no)	1996-06-24	1997-06-23	4-amino-2-ureido-pyrimidin-5-karboksylsyreamider, fremgangsmåter for deres fremstilling, legemidler inneholdendedisse forbindelsene og deres anvendelse

Country Status (11)

Country	Link
US (1)	US5773447A (2)
EP (1)	EP0816359B1 (2)
JP (1)	JP4101905B2 (2)
AT (1)	ATE281453T1 (2)
CA (1)	CA2208611C (2)
DE (2)	DE19625088A1 (2)
DK (1)	DK0816359T3 (2)
ES (1)	ES2230576T3 (2)
MX (1)	MX9704621A (2)
NO (1)	NO312133B1 (2)
PT (1)	PT816359E (2)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE19625089A1 (de) *	1996-06-24	1998-01-02	Hoechst Ag	4-Amino-2-ureido-pyrimidin-5-carbonsäureamide, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung
US7087597B1 (en)	1999-10-12	2006-08-08	Takeda Pharmaceutical Company Limited	Pyrimidine 5-carboxamide compounds, process for producing the same and use thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2853220A1 (de) *	1978-12-09	1980-07-03	Hoechst Ag	Neue amino-pyrimidin-carbanilide, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und ihre verwendung
DE3522940A1 (de) *	1985-06-27	1987-01-08	Hoechst Ag	4-amino-2-(imidazolidin-2-on-1-yl)-pyrimidin-5-carbonsaeure-(n-(3-trifluormethyl-phenyl)-amide) zur antithrombotischen prophylaxe und behandlung sowie ihre verwendung zur herstellung von antithrombotisch wirksamen arzneimitteln
DK0557879T3 (da) *	1992-02-22	1997-06-16	Hoechst Ag	4-amino-2-ureido-pyrimidin-5-carboxylsyreamider, fremgangsmåde til deres fremstilling, lægemidler med indhold af disse forbindelser og deres anvendelse
DK0557877T3 (da) *	1992-02-22	1998-04-27	Hoechst Ag	Opløselige salte af 4-amino-2-(4,4-dimethyl-imidazolidin-2-on-l-yl)-pyrimidin-5-carboxylsyre-eN-methyl-N-(3-trifluormethyl-phenyl)-amide,fremgangsmådetil deres fremstilling, deres anvendelse som lægemidler og udgangsprodukter
DE19625089A1 (de) *	1996-06-24	1998-01-02	Hoechst Ag	4-Amino-2-ureido-pyrimidin-5-carbonsäureamide, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung

1996
- 1996-06-24 DE DE19625088A patent/DE19625088A1/de not_active Withdrawn
1997
- 1997-06-12 ES ES97109548T patent/ES2230576T3/es not_active Expired - Lifetime
- 1997-06-12 AT AT97109548T patent/ATE281453T1/de active
- 1997-06-12 EP EP97109548A patent/EP0816359B1/de not_active Expired - Lifetime
- 1997-06-12 DE DE59712054T patent/DE59712054D1/de not_active Expired - Lifetime
- 1997-06-12 DK DK97109548T patent/DK0816359T3/da active
- 1997-06-12 PT PT97109548T patent/PT816359E/pt unknown
- 1997-06-13 US US08/874,255 patent/US5773447A/en not_active Expired - Lifetime
- 1997-06-20 MX MX9704621A patent/MX9704621A/es not_active IP Right Cessation
- 1997-06-23 NO NO19972942A patent/NO312133B1/no not_active IP Right Cessation
- 1997-06-23 CA CA002208611A patent/CA2208611C/en not_active Expired - Fee Related
- 1997-06-23 JP JP16581497A patent/JP4101905B2/ja not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EP0816359B1 (de)	2004-11-03
JPH1072462A (ja)	1998-03-17
ES2230576T3 (es)	2005-05-01
ATE281453T1 (de)	2004-11-15
US5773447A (en)	1998-06-30
DE59712054D1 (de)	2004-12-09
PT816359E (pt)	2005-02-28
CA2208611A1 (en)	1997-12-24
DE19625088A1 (de)	1998-01-02
EP0816359A1 (de)	1998-01-07
JP4101905B2 (ja)	2008-06-18
NO972942L (no)	1997-12-29
CA2208611C (en)	2006-10-03
MX9704621A (es)	1997-12-31
NO972942D0 (no)	1997-06-23
DK0816359T3 (da)	2005-03-14

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Date	Code	Title	Description
2015-01-26	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
JP3356751B2 (ja)	2002-12-16	糖尿病合併症治療用および予防用組成物
EP0784054B1 (en)	2001-11-28	1,2,3,4-tetrahydroquinoxalinedione derivatives and use as glutamate receptor antagonists
IL97612A (en)	1995-08-31	The history of N-transformed heterocycles, their preparation and the pharmaceutical preparations containing them
JPWO2004111012A1 (ja)	2006-08-03	イミダゾリジン誘導体
JPH05213894A (ja)	1993-08-24	Ｎ−置換ヘテロ環誘導体、製法および医薬組成物
IE852118L (en)	1986-02-28	Ethylenediamine monoamide derivatives.
LT3448B (en)	1995-10-25	Inhibitors of purine nucleoside phosphorylase and process for preparing thereof
US6753316B1 (en)	2004-06-22	Acryloyl derivatives analogous to distamycin, process for preparing them, and their use as antitumor agents
CA2089954C (en)	2002-03-26	4-amino-2-ureidopyrimidine-5-carboxamides, a process for the preparation thereof, pharmaceuticals containing these compounds, and the use thereof
JP2707936B2 (ja)	1998-02-04	β−オキソ−β−ベンゼンプロパンチオアミド誘導体
US5340814A (en)	1994-08-23	3-substituted methyl-2,3-dihydroimidazo[1,2-C] quinazoline derivatives, the preparation and use thereof
NO312133B1 (no)	2002-03-25	4-amino-2-ureido-pyrimidin-5-karboksylsyreamider, fremgangsmåter for deres fremstilling, legemidler inneholdendedisse forbindelsene og deres anvendelse
US4940712A (en)	1990-07-10	Derivatives of hydroxyprimidines as leukotriene synthesis inhibitors
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