UA65572C2 - Substituted imidazoles, intermediate compounds for the preparation thereof, a method for the preparation of substituted imidazoles and a method for the treatment of inflammatory diseases - Google Patents

Substituted imidazoles, intermediate compounds for the preparation thereof, a method for the preparation of substituted imidazoles and a method for the treatment of inflammatory diseases Download PDF

Info

Publication number: UA65572C2
Authority: UA; Ukraine
Prior art keywords: group; alkyl; substituted; fluorophenyl; imidazole
Prior art date: 1997-04-24

Application number

UA99105811A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Ortho Mcneil Pharm Inc

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.)

1997-04-24

Filing date

1998-04-17

Publication date

2004-04-15

1998-04-17 Application filed by Ortho Mcneil Pharm Inc filed Critical Ortho Mcneil Pharm Inc

2004-04-15 Publication of UA65572C2 publication Critical patent/UA65572C2/uk

Links

150000001875 compounds Chemical class 0.000 title abstract description 107
150000002460 imidazoles Chemical class 0.000 title abstract description 13
238000000034 method Methods 0.000 title description 12
238000002360 preparation method Methods 0.000 title description 5
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108090000695 Cytokines Proteins 0.000 abstract description 19
239000000543 intermediate Substances 0.000 abstract description 18
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230000002757 inflammatory effect Effects 0.000 abstract description 9
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XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 31
239000000203 mixture Substances 0.000 description 27
239000000243 solution Substances 0.000 description 25
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
-1 O-penicillamine Chemical compound 0.000 description 23
239000007787 solid Substances 0.000 description 23
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150000003839 salts Chemical class 0.000 description 20
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
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RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
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ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
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125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
229930182912 cyclosporin Natural products 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000002158 endotoxin Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
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239000004312 hexamethylene tetramine Substances 0.000 description 1
235000010299 hexamethylene tetramine Nutrition 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
150000002443 hydroxylamines Chemical class 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
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230000007246 mechanism Effects 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
238000002483 medication Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
239000008008 oral excipient Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000003544 oxime group Chemical group 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical class C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
239000006201 parenteral dosage form Substances 0.000 description 1
229960001639 penicillamine Drugs 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
208000030428 polyarticular arthritis Diseases 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
239000013641 positive control Substances 0.000 description 1
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
229960004618 prednisone Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
LJZPPWWHKPGCHS-UHFFFAOYSA-N propargyl chloride Chemical compound ClCC#C LJZPPWWHKPGCHS-UHFFFAOYSA-N 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
238000011552 rat model Methods 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical class C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000011664 signaling Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
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150000003573 thiols Chemical class 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
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Classifications

- 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
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- C07D401/14—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 three or more hetero rings
- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Rheumatology (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Epidemiology (AREA)
Pain & Pain Management (AREA)
Immunology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

UA99105811A 1997-04-24 1998-04-17 Substituted imidazoles, intermediate compounds for the preparation thereof, a method for the preparation of substituted imidazoles and a method for the treatment of inflammatory diseases UA65572C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US4425297P	1997-04-24	1997-04-24
PCT/US1998/007910 WO1998047892A1 (en)	1997-04-24	1998-04-17	Substituted imidazoles useful in the treatment of inflammatory diseases

Publications (1)

Publication Number	Publication Date
UA65572C2 true UA65572C2 (en)	2004-04-15

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ID=21931339

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UA99105811A UA65572C2 (en)	1997-04-24	1998-04-17	Substituted imidazoles, intermediate compounds for the preparation thereof, a method for the preparation of substituted imidazoles and a method for the treatment of inflammatory diseases

Country Status (24)

Country	Link
US (3)	US5965583A (no)
EP (1)	EP1028954B1 (no)
JP (1)	JP2001522357A (no)
KR (1)	KR100568438B1 (no)
CN (1)	CN1211381C (no)
AR (1)	AR012594A1 (no)
AT (1)	ATE244234T1 (no)
AU (1)	AU7138298A (no)
BR (1)	BR9808998A (no)
CA (1)	CA2297176A1 (no)
DE (1)	DE69816109T2 (no)
DK (1)	DK1028954T3 (no)
ES (1)	ES2202840T3 (no)
HU (1)	HUP0002842A3 (no)
IL (1)	IL132318A0 (no)
NO (1)	NO318937B1 (no)
NZ (1)	NZ500447A (no)
PL (1)	PL191111B1 (no)
PT (1)	PT1028954E (no)
RU (1)	RU2222534C2 (no)
TR (1)	TR199902622T2 (no)
UA (1)	UA65572C2 (no)
WO (1)	WO1998047892A1 (no)
ZA (1)	ZA983451B (no)

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US7235551B2 (en)	2000-03-02	2007-06-26	Smithkline Beecham Corporation	1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases
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- 1998-04-17 US US09/062,304 patent/US5965583A/en not_active Expired - Lifetime
- 1998-04-17 PL PL336758A patent/PL191111B1/pl not_active IP Right Cessation
- 1998-04-17 CA CA002297176A patent/CA2297176A1/en not_active Abandoned
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- 1998-04-17 CN CNB988045230A patent/CN1211381C/zh not_active Expired - Fee Related
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1999
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Publication number	Publication date
PT1028954E (pt)	2003-11-28
WO1998047892A1 (en)	1998-10-29
CN1211381C (zh)	2005-07-20
ATE244234T1 (de)	2003-07-15
NZ500447A (en)	2001-09-28
EP1028954A1 (en)	2000-08-23
AR012594A1 (es)	2000-11-08
AU7138298A (en)	1998-11-13
CA2297176A1 (en)	1998-10-29
KR100568438B1 (ko)	2006-04-07
DK1028954T3 (da)	2003-10-27
NO995095D0 (no)	1999-10-19
DE69816109T2 (de)	2004-04-22
DE69816109D1 (de)	2003-08-07
RU2222534C2 (ru)	2004-01-27
US6521655B1 (en)	2003-02-18
EP1028954B1 (en)	2003-07-02
TR199902622T2 (xx)	2000-05-22
ES2202840T3 (es)	2004-04-01
NO995095L (no)	1999-12-09
NO318937B1 (no)	2005-05-30
ZA983451B (en)	1999-10-25
CN1253558A (zh)	2000-05-17
US5965583A (en)	1999-10-12
PL191111B1 (pl)	2006-03-31
HUP0002842A3 (en)	2002-01-28
KR20010020204A (ko)	2001-03-15
PL336758A1 (en)	2000-07-17
HUP0002842A2 (hu)	2001-06-28
JP2001522357A (ja)	2001-11-13
IL132318A0 (en)	2001-03-19
BR9808998A (pt)	2000-08-08
US6214830B1 (en)	2001-04-10

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