NO320835B1 - Imidazolylderivater, anvendelse og fremstilling derav, samt farmasoytisk preparat - Google Patents
Imidazolylderivater, anvendelse og fremstilling derav, samt farmasoytisk preparat Download PDFInfo
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- NO320835B1 NO320835B1 NO20006401A NO20006401A NO320835B1 NO 320835 B1 NO320835 B1 NO 320835B1 NO 20006401 A NO20006401 A NO 20006401A NO 20006401 A NO20006401 A NO 20006401A NO 320835 B1 NO320835 B1 NO 320835B1
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- Prior art keywords
- alkyl
- compound
- group
- formula
- approx
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- 238000002360 preparation method Methods 0.000 title claims description 23
- 125000002883 imidazolyl group Chemical group 0.000 title claims description 10
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 87
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 31
- 239000003960 organic solvent Substances 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- -1 4-methyl-1-piperazinyl group Chemical group 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 206010028980 Neoplasm Diseases 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 229910052744 lithium Inorganic materials 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 5
- 208000036142 Viral infection Diseases 0.000 claims description 5
- 230000009385 viral infection Effects 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 206010016654 Fibrosis Diseases 0.000 claims description 3
- 206010017533 Fungal infection Diseases 0.000 claims description 3
- 208000031888 Mycoses Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 208000017442 Retinal disease Diseases 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 3
- 230000004761 fibrosis Effects 0.000 claims description 3
- 208000006454 hepatitis Diseases 0.000 claims description 3
- 231100000283 hepatitis Toxicity 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 208000025113 myeloid leukemia Diseases 0.000 claims description 3
- 206010061311 nervous system neoplasm Diseases 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
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- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
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- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 239000012320 chlorinating reagent Substances 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 6
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- 108010006731 Dimethylallyltranstransferase Proteins 0.000 abstract description 5
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 33
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 33
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- 239000000047 product Substances 0.000 description 17
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- 239000007864 aqueous solution Substances 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
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- 239000002585 base Substances 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 10
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- 239000002253 acid Substances 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 239000012267 brine Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 229940126214 compound 3 Drugs 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 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 6
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 5
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 5
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- 239000012867 bioactive agent Substances 0.000 description 5
- 230000003111 delayed effect Effects 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
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- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
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- 239000000654 additive Substances 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 229910000085 borane Inorganic materials 0.000 description 4
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- 150000004820 halides Chemical class 0.000 description 4
- 125000001041 indolyl group Chemical group 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- MAGGVFHZJLNEGQ-UHFFFAOYSA-N (4-chlorophenyl)-[3-(3-chlorophenyl)-1-methylsulfonyl-2,3-dihydroindol-5-yl]methanone Chemical compound C=1C=C2N(S(=O)(=O)C)CC(C=3C=C(Cl)C=CC=3)C2=CC=1C(=O)C1=CC=C(Cl)C=C1 MAGGVFHZJLNEGQ-UHFFFAOYSA-N 0.000 description 3
- SVKGMQFFVPJNOM-UHFFFAOYSA-N (4-chlorophenyl)-[3-(3-chlorophenyl)-1-methylsulfonylindol-5-yl]-(1-methylimidazol-2-yl)methanol Chemical compound CN1C=CN=C1C(O)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CN(C2=CC=1)S(C)(=O)=O)C1=CC=C(Cl)C=C1 SVKGMQFFVPJNOM-UHFFFAOYSA-N 0.000 description 3
- NRJGJWXWNMEPPM-UHFFFAOYSA-N (4-chlorophenyl)-[3-(3-chlorophenyl)-1-methylsulfonylindol-5-yl]methanone Chemical compound C12=CC(C(=O)C=3C=CC(Cl)=CC=3)=CC=C2N(S(=O)(=O)C)C=C1C1=CC=CC(Cl)=C1 NRJGJWXWNMEPPM-UHFFFAOYSA-N 0.000 description 3
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- MSZDLNDEOXWQKJ-UHFFFAOYSA-N (4-chlorophenyl)-[2-(3-chlorophenyl)-1-methylsulfonylindol-5-yl]-(3-methylimidazol-4-yl)methanol Chemical compound CN1C=NC=C1C(O)(C=1C=C2C=C(N(C2=CC=1)S(C)(=O)=O)C=1C=C(Cl)C=CC=1)C1=CC=C(Cl)C=C1 MSZDLNDEOXWQKJ-UHFFFAOYSA-N 0.000 description 2
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- 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
- 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
- C07D403/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Communicable Diseases (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8948398P | 1998-06-16 | 1998-06-16 | |
| US9814198A | 1998-06-16 | 1998-06-16 | |
| PCT/US1999/013303 WO1999065898A1 (fr) | 1998-06-16 | 1999-06-11 | Derives d'imidazolyle |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20006401D0 NO20006401D0 (no) | 2000-12-15 |
| NO20006401L NO20006401L (no) | 2000-12-15 |
| NO320835B1 true NO320835B1 (no) | 2006-01-30 |
Family
ID=26780620
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20006401A NO320835B1 (no) | 1998-06-16 | 2000-12-15 | Imidazolylderivater, anvendelse og fremstilling derav, samt farmasoytisk preparat |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1097150B1 (fr) |
| JP (1) | JP2002518387A (fr) |
| AR (1) | AR019866A1 (fr) |
| AT (1) | ATE262520T1 (fr) |
| AU (1) | AU4822299A (fr) |
| CA (1) | CA2335435A1 (fr) |
| DE (1) | DE69915835T2 (fr) |
| DK (1) | DK1097150T3 (fr) |
| ES (1) | ES2216535T3 (fr) |
| NO (1) | NO320835B1 (fr) |
| TW (1) | TW577885B (fr) |
| WO (1) | WO1999065898A1 (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2825706B1 (fr) * | 2001-06-06 | 2003-12-12 | Pf Medicament | Nouveaux derives de benzothienyle ou d'indole, leur preparation et leur utilisation comme inhibiteurs de proteines prenyl transferase |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2002859C (fr) * | 1988-11-29 | 1998-12-29 | Jean P. F. Van Wauwe | Methode de traitement d'affections epitheliales |
| GB9212833D0 (en) * | 1992-06-17 | 1992-07-29 | Glaxo Group Ltd | Chemical compounds |
| TW316902B (fr) * | 1994-12-28 | 1997-10-01 | Janssen Pharmaceutica Nv | |
| US5756528A (en) * | 1995-06-06 | 1998-05-26 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| TW349948B (en) * | 1995-10-31 | 1999-01-11 | Janssen Pharmaceutica Nv | Farnesyl transferase inhibiting 2-quinolone derivatives |
| CA2231105C (fr) * | 1995-12-08 | 2005-09-13 | Janssen Pharmaceutica N.V. | Derives de la (imidazol-5-yl)methyl-2-quinoleinone comme inhibiteur de la proteine farnesyle-transferase |
| WO1997036901A1 (fr) * | 1996-04-03 | 1997-10-09 | Merck & Co., Inc. | Inhibiteurs de transferase de farnesyl-proteine |
| TW591030B (en) * | 1997-03-10 | 2004-06-11 | Janssen Pharmaceutica Nv | Farnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N- or C-linked imidazoles |
-
1999
- 1999-06-11 JP JP2000554723A patent/JP2002518387A/ja active Pending
- 1999-06-11 CA CA002335435A patent/CA2335435A1/fr not_active Abandoned
- 1999-06-11 DE DE69915835T patent/DE69915835T2/de not_active Expired - Fee Related
- 1999-06-11 ES ES99931792T patent/ES2216535T3/es not_active Expired - Lifetime
- 1999-06-11 WO PCT/US1999/013303 patent/WO1999065898A1/fr active IP Right Grant
- 1999-06-11 AU AU48222/99A patent/AU4822299A/en not_active Abandoned
- 1999-06-11 AT AT99931792T patent/ATE262520T1/de not_active IP Right Cessation
- 1999-06-11 DK DK99931792T patent/DK1097150T3/da active
- 1999-06-11 EP EP99931792A patent/EP1097150B1/fr not_active Expired - Lifetime
- 1999-06-15 AR ARP990102856A patent/AR019866A1/es unknown
- 1999-08-19 TW TW088110018A patent/TW577885B/zh not_active IP Right Cessation
-
2000
- 2000-12-15 NO NO20006401A patent/NO320835B1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2216535T3 (es) | 2004-10-16 |
| AR019866A1 (es) | 2002-03-20 |
| NO20006401D0 (no) | 2000-12-15 |
| ATE262520T1 (de) | 2004-04-15 |
| JP2002518387A (ja) | 2002-06-25 |
| EP1097150B1 (fr) | 2004-03-24 |
| WO1999065898A1 (fr) | 1999-12-23 |
| AU4822299A (en) | 2000-01-05 |
| DE69915835D1 (de) | 2004-04-29 |
| TW577885B (en) | 2004-03-01 |
| EP1097150A1 (fr) | 2001-05-09 |
| DK1097150T3 (da) | 2004-07-26 |
| DE69915835T2 (de) | 2005-03-24 |
| NO20006401L (no) | 2000-12-15 |
| CA2335435A1 (fr) | 1999-12-23 |
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