IL132593A - Synthesis of MDRI-type acridine history - Google Patents
Synthesis of MDRI-type acridine historyInfo
- Publication number
- IL132593A IL132593A IL13259398A IL13259398A IL132593A IL 132593 A IL132593 A IL 132593A IL 13259398 A IL13259398 A IL 13259398A IL 13259398 A IL13259398 A IL 13259398A IL 132593 A IL132593 A IL 132593A
- Authority
- IL
- Israel
- Prior art keywords
- formula
- compound
- mixture
- filtered
- iii
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title description 12
- 238000003786 synthesis reaction Methods 0.000 title description 12
- 239000003112 inhibitor Substances 0.000 title description 6
- 125000000641 acridinyl group Chemical class C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 31
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000012458 free base Substances 0.000 claims abstract description 9
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000012026 peptide coupling reagents Substances 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 5
- 150000003973 alkyl amines Chemical class 0.000 claims abstract description 4
- 239000003880 polar aprotic solvent Substances 0.000 claims abstract description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 230000008878 coupling Effects 0.000 claims description 8
- 238000010168 coupling process Methods 0.000 claims description 8
- 238000005859 coupling reaction Methods 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- -1 tetrafluoroborate Chemical compound 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000003840 hydrochlorides Chemical class 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000002002 slurry Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- GDALETGZDYOOGB-UHFFFAOYSA-N Acridone Natural products C1=C(O)C=C2N(C)C3=CC=CC=C3C(=O)C2=C1O GDALETGZDYOOGB-UHFFFAOYSA-N 0.000 description 7
- FZEYVTFCMJSGMP-UHFFFAOYSA-N acridone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3NC2=C1 FZEYVTFCMJSGMP-UHFFFAOYSA-N 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000012317 TBTU Substances 0.000 description 5
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- INBURRUOTJXJKO-UHFFFAOYSA-N 1-(2-phenylethyl)isoquinolin-3-amine Chemical compound N=1C(N)=CC2=CC=CC=C2C=1CCC1=CC=CC=C1 INBURRUOTJXJKO-UHFFFAOYSA-N 0.000 description 4
- HOXCITDDHKZNLF-UHFFFAOYSA-N 3-nitro-1-(2-phenylethyl)isoquinoline Chemical compound N=1C([N+](=O)[O-])=CC2=CC=CC=C2C=1CCC1=CC=CC=C1 HOXCITDDHKZNLF-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 150000001251 acridines Chemical class 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- NTURQZFFJDCTMZ-UHFFFAOYSA-N 1-(2-bromoethyl)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(CCBr)C=C1 NTURQZFFJDCTMZ-UHFFFAOYSA-N 0.000 description 2
- XRXMNWGCKISMOH-UHFFFAOYSA-N 2-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Br XRXMNWGCKISMOH-UHFFFAOYSA-N 0.000 description 2
- SXOPCLUOUFQBJV-UHFFFAOYSA-N 3-methoxyanthranilic acid Chemical compound COC1=CC=CC(C(O)=O)=C1N SXOPCLUOUFQBJV-UHFFFAOYSA-N 0.000 description 2
- SHOWAGCIRTUYNA-UHFFFAOYSA-N 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline;hydron;chloride Chemical compound [Cl-].C1C[NH2+]CC2=C1C=C(OC)C(OC)=C2 SHOWAGCIRTUYNA-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 2
- 230000001235 sensitizing effect Effects 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- KVWFUYIAYGFNIM-UHFFFAOYSA-N 1-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound N1C2=CC=CC=C2C(=O)C2=C1C(C(N)=O)=CC=C2OC KVWFUYIAYGFNIM-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- ZLMJMSJWJFRBEC-LZFNBGRKSA-N Potassium-45 Chemical compound [45K] ZLMJMSJWJFRBEC-LZFNBGRKSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical class C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 229940125665 acridine carboxamide Drugs 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940027998 antiseptic and disinfectant acridine derivative Drugs 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- OSFCMRGOZNQUSW-UHFFFAOYSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound N1C2=C(OC)C=CC=C2C(=O)C2=C1C(C(=O)NC1=CC=C(C=C1)CCN1CCC=3C=C(C(=CC=3C1)OC)OC)=CC=C2 OSFCMRGOZNQUSW-UHFFFAOYSA-N 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C07D219/06—Oxygen 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
- C07D401/02—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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Steroid Compounds (AREA)
- Pyridine Compounds (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9710612.4A GB9710612D0 (en) | 1997-05-23 | 1997-05-23 | Synthesis of acridine derivatives |
| PCT/EP1998/002991 WO1998052923A1 (en) | 1997-05-23 | 1998-05-22 | Synthesis of acridine derivative multidrug-resistant inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL132593A0 IL132593A0 (en) | 2001-03-19 |
| IL132593A true IL132593A (en) | 2004-07-25 |
Family
ID=10812906
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13259398A IL132593A (en) | 1997-05-23 | 1998-05-22 | Synthesis of MDRI-type acridine history |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US6248891B1 (de) |
| EP (1) | EP0983246B1 (de) |
| JP (1) | JP4390861B2 (de) |
| KR (1) | KR100536155B1 (de) |
| CN (1) | CN1178918C (de) |
| AT (1) | ATE228506T1 (de) |
| AU (1) | AU744402B2 (de) |
| BR (1) | BR9809143A (de) |
| CA (1) | CA2289492C (de) |
| DE (1) | DE69809733T2 (de) |
| DK (1) | DK0983246T3 (de) |
| ES (1) | ES2187984T3 (de) |
| GB (1) | GB9710612D0 (de) |
| HK (1) | HK1023995A1 (de) |
| HU (1) | HUP0002083A3 (de) |
| IL (1) | IL132593A (de) |
| PL (1) | PL190109B1 (de) |
| PT (1) | PT983246E (de) |
| WO (1) | WO1998052923A1 (de) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9708805D0 (en) | 1997-05-01 | 1997-06-25 | Smithkline Beecham Plc | Compounds |
| GB9810876D0 (en) | 1998-05-20 | 1998-07-22 | Smithkline Beecham Plc | Compounds |
| MA26696A1 (fr) | 1998-10-08 | 2004-12-20 | Smithkline Beecham Plc | Derives de tetrahydrobenzazepine nouveaux, procede pour leur preparation et compositions pharmaceutiques les contenant |
| DK1189637T3 (da) * | 1999-05-17 | 2006-12-11 | Cancer Res Ventures Ltd | Produkter til forbedring af biotilgængeligheden for oralt indgivne medikamenter |
| SI21507A (sl) | 2003-05-16 | 2004-12-31 | LEK farmacevtska dru�ba d.d. | Postopek za pripravo spojin z ace inhibitornim delovanjem |
| US7829578B1 (en) | 2005-12-12 | 2010-11-09 | Oregon Health & Science University | Aromatic ketones and uses thereof |
| WO2008064011A1 (en) | 2006-11-13 | 2008-05-29 | The Government Of The U.S. Of America As Represented By The Department Of Veterans Affairs | Acridone compounds |
| US8598354B2 (en) | 2008-12-05 | 2013-12-03 | University Of South Florida | Compounds having antiparasitic or anti-infectious activity |
| IL277335B2 (en) * | 2018-03-21 | 2024-03-01 | Izumi Tech Llc | Analogues of alcridar with deuterium |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2783680B2 (ja) * | 1991-01-11 | 1998-08-06 | ラボラトワール、グラクソ、ソシエテ、アノニム | アクリジン誘導体 |
| CZ104197A3 (en) * | 1994-10-05 | 1997-09-17 | Glaxo Wellcome Inc | Pharmaceutical preparation |
-
1997
- 1997-05-23 GB GBGB9710612.4A patent/GB9710612D0/en active Pending
-
1998
- 1998-05-22 PL PL98336937A patent/PL190109B1/pl not_active IP Right Cessation
- 1998-05-22 CA CA002289492A patent/CA2289492C/en not_active Expired - Fee Related
- 1998-05-22 KR KR10-1999-7010781A patent/KR100536155B1/ko not_active IP Right Cessation
- 1998-05-22 DE DE69809733T patent/DE69809733T2/de not_active Expired - Lifetime
- 1998-05-22 CN CNB988051265A patent/CN1178918C/zh not_active Expired - Fee Related
- 1998-05-22 WO PCT/EP1998/002991 patent/WO1998052923A1/en active IP Right Grant
- 1998-05-22 AT AT98934892T patent/ATE228506T1/de not_active IP Right Cessation
- 1998-05-22 IL IL13259398A patent/IL132593A/en not_active IP Right Cessation
- 1998-05-22 ES ES98934892T patent/ES2187984T3/es not_active Expired - Lifetime
- 1998-05-22 US US09/403,158 patent/US6248891B1/en not_active Expired - Fee Related
- 1998-05-22 EP EP98934892A patent/EP0983246B1/de not_active Expired - Lifetime
- 1998-05-22 BR BR9809143-3A patent/BR9809143A/pt not_active Application Discontinuation
- 1998-05-22 HU HU0002083A patent/HUP0002083A3/hu unknown
- 1998-05-22 JP JP54995998A patent/JP4390861B2/ja not_active Expired - Fee Related
- 1998-05-22 AU AU84344/98A patent/AU744402B2/en not_active Ceased
- 1998-05-22 PT PT98934892T patent/PT983246E/pt unknown
- 1998-05-22 DK DK98934892T patent/DK0983246T3/da active
-
2000
- 2000-05-25 HK HK00103130A patent/HK1023995A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0983246A1 (de) | 2000-03-08 |
| KR100536155B1 (ko) | 2005-12-14 |
| CA2289492C (en) | 2009-03-24 |
| JP2002502371A (ja) | 2002-01-22 |
| JP4390861B2 (ja) | 2009-12-24 |
| BR9809143A (pt) | 2000-08-01 |
| US6248891B1 (en) | 2001-06-19 |
| PT983246E (pt) | 2003-04-30 |
| AU744402B2 (en) | 2002-02-21 |
| KR20010012817A (ko) | 2001-02-26 |
| DE69809733D1 (de) | 2003-01-09 |
| HUP0002083A3 (en) | 2002-03-28 |
| ES2187984T3 (es) | 2003-06-16 |
| HK1023995A1 (en) | 2000-09-29 |
| CN1255918A (zh) | 2000-06-07 |
| PL190109B1 (pl) | 2005-10-31 |
| IL132593A0 (en) | 2001-03-19 |
| HUP0002083A2 (hu) | 2001-04-28 |
| CN1178918C (zh) | 2004-12-08 |
| CA2289492A1 (en) | 1998-11-26 |
| GB9710612D0 (en) | 1997-07-16 |
| DE69809733T2 (de) | 2003-09-18 |
| EP0983246B1 (de) | 2002-11-27 |
| ATE228506T1 (de) | 2002-12-15 |
| PL336937A1 (en) | 2000-07-17 |
| WO1998052923A1 (en) | 1998-11-26 |
| DK0983246T3 (da) | 2003-03-24 |
| AU8434498A (en) | 1998-12-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2461060C (en) | Method for preparing pyrimidinone compound and pharmaceutically acceptable salts thereof | |
| EP0983246B1 (de) | Synthese von acridinderivaten als inhibitoren von multipler medikamentenresistenz | |
| AU2001292386A1 (en) | Method for preparing pyrimidinone compound and pharmaceutically acceptable salts thereof | |
| JP2013531004A (ja) | トロンビン特異的インヒビターの調製のための中間体及び方法 | |
| JPH0479349B2 (de) | ||
| JP2004520446A (ja) | ロサルタンカリウムの結晶化方法 | |
| JP2008531642A (ja) | 薬学活性化合物イルベサルタンおよびその合成中間体を得る方法 | |
| JP4208463B2 (ja) | キノロンカルボン酸誘導体の製造に関する中間体 | |
| US10501403B2 (en) | Method for preparation of (S)-N1-(2-aminoethyl)-3-(4-alkoxyphenyl)propane-1,2-diamine trihydrochloride | |
| KR100617953B1 (ko) | 피리미디논 화합물 및 이의 염의 제조방법 | |
| KR102702677B1 (ko) | 피마살탄 및 그의 제조 중간체의 제조방법 | |
| KR101457453B1 (ko) | 게피티닙의 제조방법 및 이의 제조에 사용되는 중간체 | |
| JP2648165B2 (ja) | ベルゾ（カルコゲノ）〔４，３，２−ｃｄ〕インダゾールの調製方法 | |
| KR100368895B1 (ko) | 1,2,3,9-테트라하이드로-9-메틸-3-[(2-메틸-1ｈ-이미다졸-1-일)메틸]-4ｈ-카바졸-4-온의 제조방법 | |
| JPH0211562A (ja) | ４―メチル―３―チオセミカルバジドの製造法 | |
| KR20190110400A (ko) | 새로운 중간체를 이용한 바제독시펜의 제조방법 | |
| SK283182B6 (sk) | Spôsob prípravy 5-(alkoxymetyl)-2,3-pyridíndikarboximidových zlúčenín a medziproduktov na tento spôsob | |
| CA2570179A1 (en) | Method for producing acetamidopyrrolidine derivative and intermediate compound thereof | |
| CA2629836A1 (en) | Benzeneszkfibate salts and their use as intermediates for the synthesis of 2-[2-(1-alkyl-2-piperidyl)ethyl] cinnamanilides | |
| JPS62132867A (ja) | イミダゾ−ル誘導体の製法 | |
| JP2001278865A (ja) | ４−アミノキノリン類の製造方法 | |
| JP2001278864A (ja) | ４−メトキシキノリン類の製造方法 | |
| EP1966205A2 (de) | Erstellung von 1h-imidazo[4,5-c]quinolin-4-aminen mithilfe von 1h-imidazo[4,5-c]quinolin-4-phthalimid-vermittlern |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |