EE03484B1 - Farnesüülproteiintransferaasi inhibeerivad (5-imidasolüül)metüül-2-kinolinooni derivaadid ja nende kasutamine - Google Patents
Farnesüülproteiintransferaasi inhibeerivad (5-imidasolüül)metüül-2-kinolinooni derivaadid ja nende kasutamineInfo
- Publication number
- EE03484B1 EE03484B1 EE9800146A EE9800146A EE03484B1 EE 03484 B1 EE03484 B1 EE 03484B1 EE 9800146 A EE9800146 A EE 9800146A EE 9800146 A EE9800146 A EE 9800146A EE 03484 B1 EE03484 B1 EE 03484B1
- Authority
- EE
- Estonia
- Prior art keywords
- imidazolyl
- methyl
- protein transferase
- farnesyl protein
- quinolinone derivatives
- Prior art date
Links
- AVGQUILLCRPWKH-UHFFFAOYSA-N 4-(1h-imidazol-5-yl)-3-methyl-1h-quinolin-2-one Chemical class C12=CC=CC=C2NC(=O)C(C)=C1C1=CN=CN1 AVGQUILLCRPWKH-UHFFFAOYSA-N 0.000 title 1
- 102000004357 Transferases Human genes 0.000 title 1
- 108090000992 Transferases Proteins 0.000 title 1
- 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 title 1
- 230000002401 inhibitory effect Effects 0.000 title 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon 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
- A61K31/435—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
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP95203427 | 1995-12-08 | ||
| PCT/EP1996/004515 WO1997021701A1 (en) | 1995-12-08 | 1996-10-16 | Farnesyl protein transferase inhibiting (imidazol-5-yl)methyl-2-quinolinone derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EE9800146A EE9800146A (et) | 1998-10-15 |
| EE03484B1 true EE03484B1 (et) | 2001-08-15 |
Family
ID=8220926
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EE9800146A EE03484B1 (et) | 1995-12-08 | 1996-10-16 | Farnesüülproteiintransferaasi inhibeerivad (5-imidasolüül)metüül-2-kinolinooni derivaadid ja nende kasutamine |
Country Status (36)
| Country | Link |
|---|---|
| US (3) | US6037350A (et) |
| EP (2) | EP0865440B1 (et) |
| JP (1) | JP3257559B2 (et) |
| KR (1) | KR100272676B1 (et) |
| CN (1) | CN1101392C (et) |
| AP (1) | AP1108A (et) |
| AR (1) | AR004992A1 (et) |
| AT (2) | ATE321757T1 (et) |
| AU (1) | AU711142B2 (et) |
| BG (1) | BG62615B1 (et) |
| BR (1) | BR9610745A (et) |
| CA (1) | CA2231105C (et) |
| CY (1) | CY2289B1 (et) |
| CZ (1) | CZ293296B6 (et) |
| DE (2) | DE69635966T2 (et) |
| DK (2) | DK0865440T3 (et) |
| EA (1) | EA000710B1 (et) |
| EE (1) | EE03484B1 (et) |
| ES (2) | ES2175137T3 (et) |
| HK (1) | HK1042482B (et) |
| HR (1) | HRP960576B1 (et) |
| HU (1) | HU221227B1 (et) |
| IL (1) | IL123568A (et) |
| MX (1) | MX9802068A (et) |
| MY (1) | MY114444A (et) |
| NO (1) | NO314036B1 (et) |
| NZ (1) | NZ320244A (et) |
| PL (1) | PL184171B1 (et) |
| PT (2) | PT865440E (et) |
| SI (2) | SI0865440T1 (et) |
| SK (1) | SK283335B6 (et) |
| TR (1) | TR199800825T2 (et) |
| TW (1) | TW494101B (et) |
| UA (1) | UA57717C2 (et) |
| WO (1) | WO1997021701A1 (et) |
| ZA (1) | ZA9610254B (et) |
Families Citing this family (240)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EE03484B1 (et) * | 1995-12-08 | 2001-08-15 | Janssen Pharmaceutica N.V. | Farnesüülproteiintransferaasi inhibeerivad (5-imidasolüül)metüül-2-kinolinooni derivaadid ja nende kasutamine |
| ATE222104T1 (de) | 1997-06-02 | 2002-08-15 | Janssen Pharmaceutica Nv | (imidazol-5-yl)methyl-2-quinolinone derivativen als inhibitoren von proliferation der glatten muskelzellen |
| US20030114503A1 (en) * | 1997-06-16 | 2003-06-19 | Pfizer Inc. | Farnesyl transferase inhibitors in combination with HMG CoA reductase inhibitors for the treatment of cancer |
| AU4822299A (en) * | 1998-06-16 | 2000-01-05 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Imidazolyl derivatives |
| US6420555B1 (en) | 1998-06-16 | 2002-07-16 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | Imidazolyl derivatives |
| US6545020B1 (en) | 1998-07-06 | 2003-04-08 | Janssen Pharmaceutica, N.V. | Farnesyl Protein transferase inhibitors with in vivo radiosensitizing properties |
| HRP20000904A2 (en) * | 1998-07-06 | 2001-12-31 | Janssen Pharmaceutica Nv | Farnesyl protein transferase inhibitors for treating arthropathies |
| FR2780892B1 (fr) * | 1998-07-08 | 2001-08-17 | Sod Conseils Rech Applic | Utilisation d'inhibiteurs de prenyltransferases pour preparer un medicament destine a traiter les pathologies qui resultent de la fixation membranaire de la proteine g heterotrimerique |
| ATE289602T1 (de) * | 1998-08-27 | 2005-03-15 | Pfizer Prod Inc | Quinolin-2-on-derivate verwendbar als antikrebsmittel |
| TR200101343T2 (tr) | 1998-08-27 | 2001-09-21 | Pfizer Products Inc. | Kansere karşı kullanılan maddeler olarak alkinil-ikame edilmiş kinolin-2-on türevleri |
| US6316436B1 (en) | 1998-12-08 | 2001-11-13 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| US6284755B1 (en) | 1998-12-08 | 2001-09-04 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| BR9916827A (pt) | 1998-12-23 | 2001-10-16 | Janssen Pharmaceutica Nv | Derivados de quinolina 1,2-anelados |
| JP3270834B2 (ja) | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | 抗がん剤として有用なヘテロ芳香族二環式誘導体 |
| UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| KR20010102073A (ko) | 1999-02-11 | 2001-11-15 | 실버스타인 아써 에이. | 항암제로 유용한 헤테로아릴-치환된 퀴놀린-2-온 유도체 |
| US6143766A (en) * | 1999-04-16 | 2000-11-07 | Warner-Lambert Company | Benzopyranone and quinolone inhibitors of ras farnesyl transferase |
| EP1420015A1 (en) * | 1999-06-11 | 2004-05-19 | Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S. | Imidazolyl derivatives |
| FR2796943A1 (fr) * | 1999-07-30 | 2001-02-02 | Aventis Pharma Sa | Derives de benzoxazinnes, leur procede de preparation et leur utilisation en therapeutique |
| AU1400401A (en) * | 1999-11-09 | 2001-06-06 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Product inhibiting transduction of G heterotrimeric protein signals combined with another anti-cancer agent for therapeutic use in cancer treatment |
| DE60008206T2 (de) * | 1999-11-30 | 2004-12-02 | Pfizer Products Inc., Groton | Chinolinderivate verwendbar zur Hemmung der Farnesyl-Protein Transferase |
| HN2000000266A (es) * | 2000-01-21 | 2001-05-21 | Pfizer Prod Inc | Compuesto anticanceroso y metodo de separacion de enantiomeros util para sintetizar dicho compuesto. |
| SI1255537T1 (sl) * | 2000-02-04 | 2006-10-31 | Janssen Pharmaceutica Nv | Inhibitorji farnezil protein transferaze za zdravljenje raka dojk |
| US6838467B2 (en) | 2000-02-24 | 2005-01-04 | Janssen Pharmaceutica N. V. | Dosing regimen |
| US20030212008A1 (en) * | 2000-02-29 | 2003-11-13 | Palmer Peter Albert | Farnesyl protein transferase inhibitor combinations with further anti-cancer agents |
| CA2397253A1 (en) * | 2000-02-29 | 2001-09-07 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with anti-tumor anthracycline derivatives |
| EP1261342A2 (en) * | 2000-02-29 | 2002-12-04 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations |
| JP2003525234A (ja) * | 2000-02-29 | 2003-08-26 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | カンプトテシン化合物とのファルネシルタンパク質トランスフェラーゼ阻害剤の組み合わせ剤 |
| EP1261348A2 (en) * | 2000-02-29 | 2002-12-04 | Janssen Pharmaceutica N.V. | Combinations of a farnesyl protein transferase inhibitor with nitrogen mustard or nitrosourea alkylating agents |
| WO2001064195A2 (en) * | 2000-02-29 | 2001-09-07 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with anti-tumor nucleoside derivatives |
| US20030181473A1 (en) * | 2000-02-29 | 2003-09-25 | Palmer Peter Albert | Farnesyl protein transferase inhibitor combinations with taxane compounds |
| US20030022918A1 (en) * | 2000-02-29 | 2003-01-30 | Horak Ivan David | Farnesyl protein transferase inhibitor combinations with an her2 antibody |
| AU2001239275A1 (en) * | 2000-02-29 | 2001-09-12 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with anti-tumor podophyllotoxin derivatives |
| CA2397475A1 (en) * | 2000-02-29 | 2001-09-07 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with vinca alkaloids |
| CA2397657A1 (en) * | 2000-02-29 | 2001-09-07 | Janssen Pharmaceutica Inc. | Farnesyl protein transferase inhibitor combinations with platinum compounds |
| US6844357B2 (en) * | 2000-05-01 | 2005-01-18 | Pfizer Inc. | Substituted quinolin-2-one derivatives useful as antiproliferative agents |
| JO2361B1 (en) * | 2000-06-22 | 2006-12-12 | جانسين فارماسيوتيكا ان. في | Enaniumer 1,2-anylated quinoline inhibitor for the transporter - farnesyl |
| WO2002024686A2 (en) | 2000-09-25 | 2002-03-28 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting 6-heterocyclylmethyl quinoline and quinazoline derivatives |
| US7173040B2 (en) | 2000-09-25 | 2007-02-06 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting 6-[(substituted phenyl)methyl]-quinoline and quinazoline derinazoline derivatives |
| ATE321038T1 (de) | 2000-09-25 | 2006-04-15 | Janssen Pharmaceutica Nv | Chinolin- und chinazolinderivate und deren verwendung als farnesyl transferase inhibitoren |
| JP4974439B2 (ja) | 2000-09-25 | 2012-07-11 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ファルネシルトランスフェラーゼを阻害する6−ヘテロシクリルメチルキノリノン誘導体 |
| DE60139080D1 (de) | 2000-11-21 | 2009-08-06 | Janssen Pharmaceutica Nv | Farnesyltransferase hemmende benzoheterocyclische derivate |
| WO2002043733A1 (en) * | 2000-11-28 | 2002-06-06 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitors for the treatment of inflammatory bowel disease |
| AU2002218436A1 (en) * | 2000-12-19 | 2002-07-01 | Pfizer Products Inc. | Crystal forms of 6-((4-chloro-phenyl) -hydroxy-(-3-methyl- 3h-imidaol-4-yl) -methyl) -4-(3-ethynyl-phenyl) -1-methyl-1h- quinolin-2-one, 2,3- dihydroxybutanedioate salts and method of production |
| US20040067968A1 (en) * | 2000-12-27 | 2004-04-08 | Angibaud Patrick Rene | Farnesyl transferase inhibiting 4-heterocyclyl quinoline and quinazoline |
| WO2002051835A1 (en) * | 2000-12-27 | 2002-07-04 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting 4-substituted quinoline and quinazoline derivatives |
| AU2002236813A1 (en) * | 2001-01-22 | 2002-07-30 | Schering Corporation | Treatment of malaria with farnesyl protein transferase inhibitors |
| ES2318000T3 (es) * | 2001-02-15 | 2009-05-01 | Janssen Pharmaceutica Nv | Combinaciones de inhibidores de la farnesil-protein-transferasa con agentes antiestrogenos. |
| EA006770B1 (ru) * | 2001-03-12 | 2006-04-28 | Янссен Фармацевтика Н.В. | Способ получения соединений имидазола |
| US20020151563A1 (en) * | 2001-03-29 | 2002-10-17 | Pfizer Inc. | Farnesyl transferase inhibitors in combination with HMG CoA reductase inhibitors for the inhibition of abnormal cell growth |
| EP1408971A4 (en) * | 2001-06-21 | 2006-01-25 | Ariad Pharma Inc | NEW QUINOLINES AND THEIR USES |
| EP1412367A4 (en) * | 2001-06-21 | 2006-05-03 | Ariad Pharma Inc | NEW CHINOLINE AND ITS USE |
| US6740757B2 (en) | 2001-08-29 | 2004-05-25 | Pfizer Inc | Enantiomers of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3h-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl]-1-methyl-1h-quinolin-2-one and salts thereof, useful in the treatment of cancer |
| US20030134846A1 (en) * | 2001-10-09 | 2003-07-17 | Schering Corporation | Treatment of trypanosoma brucei with farnesyl protein transferase inhibitors |
| EP1458720B1 (en) | 2001-12-19 | 2009-03-18 | Janssen Pharmaceutica N.V. | 1,8-annelated quinoline derivatives substituted with carbon-linked triazoles as farnesyl transferase inhibitors |
| ATE364384T1 (de) * | 2002-03-22 | 2007-07-15 | Janssen Pharmaceutica Nv | Benzylimidazolyl substituierte 2-chinolon und chinazolinon derivate zur verwendung als farnesyl transferase inhibitoren |
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| GB2101115A (en) * | 1980-10-23 | 1983-01-12 | Pfizer Ltd | Thromboxane synthetase inhibitors |
| CA2002864C (en) * | 1988-11-29 | 1999-11-16 | Eddy J. E. Freyne | (1h-azol-1-ylmethyl) substituted quinoline, quinazoline or quinoxaline derivatives |
| EE03484B1 (et) * | 1995-12-08 | 2001-08-15 | Janssen Pharmaceutica N.V. | Farnesüülproteiintransferaasi inhibeerivad (5-imidasolüül)metüül-2-kinolinooni derivaadid ja nende kasutamine |
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