CA2208611C - 4-amino-2-ureidopyrimidine-5-carboxamides, processes for their preparation, pharmaceuticals comprising these compounds, and their use - Google Patents

4-amino-2-ureidopyrimidine-5-carboxamides, processes for their preparation, pharmaceuticals comprising these compounds, and their use Download PDF

Info

Publication number: CA2208611C
Authority: CA; Canada
Prior art keywords: formula; compound; alkyl; fluorine; pyrimidine
Prior art date: 1996-06-24
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 - Fee Related

Application number

CA002208611A

Other languages

English (en)

French (fr)

Other versions

CA2208611A1 (en

Inventor

Gerhard Rackur

Hans Georg Boger

Norbert Krass

Axel Hoffmann

Michael Leineweber

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Hoechst AG

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

2006-10-03

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

1997-12-24 Publication of CA2208611A1 publication Critical patent/CA2208611A1/en

2006-10-03 Application granted granted Critical

2006-10-03 Publication of CA2208611C publication Critical patent/CA2208611C/en

2017-06-23 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 97
238000000034 method Methods 0.000 title claims abstract description 45
238000002360 preparation method Methods 0.000 title claims abstract description 29
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 abstract description 5
239000003814 drug Substances 0.000 title description 4
150000003839 salts Chemical class 0.000 claims abstract description 20
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
208000035475 disorder Diseases 0.000 claims abstract description 5
230000037356 lipid metabolism Effects 0.000 claims abstract description 5
-1 -O-(C1-C8)-alkyl Chemical group 0.000 claims description 27
239000011737 fluorine Substances 0.000 claims description 24
229910052731 fluorine Inorganic materials 0.000 claims description 24
239000002904 solvent Substances 0.000 claims description 15
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
239000000460 chlorine Chemical group 0.000 claims description 12
229910052801 chlorine Inorganic materials 0.000 claims description 12
125000001153 fluoro group Chemical group F* 0.000 claims description 12
239000001257 hydrogen Chemical group 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 9
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
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 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
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
UEWDJCZJEIBPKX-UHFFFAOYSA-N 2,2-diethoxy-1-methylpyrrolidine Chemical compound CCOC1(OCC)CCCN1C UEWDJCZJEIBPKX-UHFFFAOYSA-N 0.000 claims description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical group [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
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 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
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 3
239000008194 pharmaceutical composition Substances 0.000 claims 1
239000000203 mixture Substances 0.000 description 31
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
238000005160 1H NMR spectroscopy Methods 0.000 description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 22
150000003857 carboxamides Chemical class 0.000 description 20
108020004999 messenger RNA Proteins 0.000 description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
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QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
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XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
210000003494 hepatocyte Anatomy 0.000 description 8
239000013078 crystal Substances 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
230000004060 metabolic process Effects 0.000 description 7
239000000825 pharmaceutical preparation Substances 0.000 description 7
239000012071 phase Substances 0.000 description 7
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 6
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
125000000217 alkyl group Chemical group 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
239000000126 substance Substances 0.000 description 6
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238000005481 NMR spectroscopy Methods 0.000 description 5
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230000015572 biosynthetic process Effects 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
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DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-UHFFFAOYSA-N 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
239000000047 product Substances 0.000 description 4
238000000746 purification Methods 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
238000010792 warming Methods 0.000 description 4
DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 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
230000007717 exclusion Effects 0.000 description 3
239000012362 glacial acetic acid 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
239000007788 liquid Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
238000002156 mixing Methods 0.000 description 3
239000000843 powder Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
239000000523 sample Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
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125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
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
SVOQOFSQLVVHKQ-UHFFFAOYSA-N 6-oxo-1h-pyrimidine-5-carbonitrile Chemical class O=C1NC=NC=C1C#N SVOQOFSQLVVHKQ-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
229940126062 Compound A Drugs 0.000 description 2
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239000013543 active substance Substances 0.000 description 2
MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
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IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
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MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
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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
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DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
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UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
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239000000314 lubricant Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
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239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
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CALISYPJESQWEI-UHFFFAOYSA-N n-(2,2,3,3,4,4,4-heptafluorobutyl)-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC=CC(NCC(F)(F)C(F)(F)C(F)(F)F)=C1 CALISYPJESQWEI-UHFFFAOYSA-N 0.000 description 1
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VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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230000036470 plasma concentration Effects 0.000 description 1
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239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
108090000623 proteins and genes Proteins 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
150000003230 pyrimidines Chemical class 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)

CA002208611A 1996-06-24 1997-06-23 4-amino-2-ureidopyrimidine-5-carboxamides, processes for their preparation, pharmaceuticals comprising these compounds, and their use Expired - Fee Related CA2208611C (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19625088.9		1996-06-24
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 (2)

Publication Number	Publication Date
CA2208611A1 CA2208611A1 (en)	1997-12-24
CA2208611C true CA2208611C (en)	2006-10-03

Family

ID=7797761

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002208611A Expired - Fee Related CA2208611C (en)	1996-06-24	1997-06-23	4-amino-2-ureidopyrimidine-5-carboxamides, processes for their preparation, pharmaceuticals comprising these compounds, and their use

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
NO312133B1 (no)	2002-03-25
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
MX9704621A (es)	1997-12-31
NO972942D0 (no)	1997-06-23
DK0816359T3 (da)	2005-03-14

Legal Events

Date	Code	Title	Description
2002-06-21	EEER	Examination request
2015-08-04	MKLA	Lapsed	Effective date: 20150623

Publication	Publication Date	Title
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US5155110A (en)	1992-10-13	Fenamic acid hydroxamate derivatives having cyclooxygenase and 5-lipoxygenase inhibition
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EP1911755B1 (en)	2011-09-14	Benzoimidazole compound capable of inhibiting prostaglandin d synthetase
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
HU218487B (hu)	2000-09-28	N-Ciano-piridin-karboximid-amid-származékok, ilyen vegyületeket tartalmazó gyógyászati készítmények és eljárás a vegyületek előállítására
FI105029B (fi)	2000-05-31	Menetelmä terapeuttisesti käyttökelpoisten 4-amino-2-ureido-pyrimidiini-5-karboksyylihappoamidien valmistamiseksi, välituotteita ja niiden valmistus
CA2208611C (en)	2006-10-03	4-amino-2-ureidopyrimidine-5-carboxamides, processes for their preparation, pharmaceuticals comprising these compounds, and their use
US5340814A (en)	1994-08-23	3-substituted methyl-2,3-dihydroimidazo[1,2-C] quinazoline derivatives, the preparation and use thereof
RU2200737C2 (ru)	2003-03-20	Пиримидо[4,5-b]индолы и промежуточное соединение (варианты)
CA2208630C (en)	2006-07-11	4-amino-2-ureidopyrimidine-5-carboxamides, processes for their preparation, pharmaceuticals comprising these compounds, and their use
US4912135A (en)	1990-03-27	Amide compounds
EP0143001B1 (en)	1991-04-10	Pyrimidoisoquinoline derivatives
US5795899A (en)	1998-08-18	Soluble salts of 4-amino-2-(4,4-dimethylimidazolidin-2-on-1-yl) pyrimidine-5-carboxylic acid N-methyl-N-(3-trifluoromethylphenyl)-amide, a process for the preparation thereof, the use thereof as pharmaceuticals and starting materials
EP0131973A1 (en)	1985-01-23	New amidine derivatives of 2-substituted 4-phenilimidazole
US7078425B2 (en)	2006-07-18	Preparation of phosphatase inhibitors
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US5482942A (en)	1996-01-09	(3,4-dioxocyclobuten-1-yl)chromene, indene, and dihydronaphthalenone derivatives as smooth muscle relaxants
JPH0641072A (ja)	1994-02-15	新規なイサチン誘導体又はその塩
EP0685467A1 (en)	1995-12-06	Novel pyrimidine derivative and medicinal composition
ES2371358T3 (es)	2011-12-30	Compuesto de benzoimidazol capaz de inhibir prostaglandina d sintetasa.
JPH0558634B2 (2)	1993-08-27