NO321933B1 - Fremgangsmate for fremstilling av (-)cis-3-hydroksy-1-metyl-4-(2,4,6-trimetoksyfenyl)-piperidin og mellomprodukter. - Google Patents
Fremgangsmate for fremstilling av (-)cis-3-hydroksy-1-metyl-4-(2,4,6-trimetoksyfenyl)-piperidin og mellomprodukter. Download PDFInfo
- Publication number
- NO321933B1 NO321933B1 NO20003454A NO20003454A NO321933B1 NO 321933 B1 NO321933 B1 NO 321933B1 NO 20003454 A NO20003454 A NO 20003454A NO 20003454 A NO20003454 A NO 20003454A NO 321933 B1 NO321933 B1 NO 321933B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- trimethoxyphenyl
- hydroxy
- tetrahydro
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 17
- 238000002360 preparation method Methods 0.000 title claims description 14
- MGNNDUKLPNLAFW-NWDGAFQWSA-N (3s,4r)-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidin-3-ol Chemical compound COC1=CC(OC)=CC(OC)=C1[C@@H]1[C@H](O)CN(C)CC1 MGNNDUKLPNLAFW-NWDGAFQWSA-N 0.000 title claims description 4
- 239000000543 intermediate Substances 0.000 title description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- RUOBYKJSLYFVNY-UHFFFAOYSA-N 1-methyl-4-(2,4,6-trimethoxyphenyl)-3,6-dihydro-2h-pyridin-3-ol Chemical compound COC1=CC(OC)=CC(OC)=C1C1=CCN(C)CC1O RUOBYKJSLYFVNY-UHFFFAOYSA-N 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 22
- 239000000047 product Substances 0.000 claims description 14
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- LKUDPHPHKOZXCD-UHFFFAOYSA-N 1,3,5-trimethoxybenzene Chemical compound COC1=CC(OC)=CC(OC)=C1 LKUDPHPHKOZXCD-UHFFFAOYSA-N 0.000 claims description 12
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- ITPBYEUERJAVHH-UHFFFAOYSA-N 3-bromo-1-methyl-4-(2,4,6-trimethoxyphenyl)-3,6-dihydro-2h-pyridine;hydrobromide Chemical compound Br.COC1=CC(OC)=CC(OC)=C1C1=CCN(C)CC1Br ITPBYEUERJAVHH-UHFFFAOYSA-N 0.000 claims description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 10
- 229960000583 acetic acid Drugs 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- 239000012362 glacial acetic acid Substances 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- 239000002244 precipitate Substances 0.000 claims description 7
- 239000011541 reaction mixture Substances 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- 238000003776 cleavage reaction Methods 0.000 claims description 6
- 230000007017 scission Effects 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- 150000004808 allyl alcohols Chemical class 0.000 claims description 4
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 3
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000008346 aqueous phase Substances 0.000 claims description 2
- 230000031709 bromination Effects 0.000 claims description 2
- 238000005893 bromination reaction Methods 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims description 2
- 230000036571 hydration Effects 0.000 claims description 2
- 238000006703 hydration reaction Methods 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 5
- BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- LFBJHARYMYDANW-JIOHBXSKSA-N (3S,4R)-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidin-3-ol Chemical compound O[C@@H]1CN(CC[C@@H]1C1=C(C=C(C=C1OC)OC)OC)C.O[C@@H]1CN(CC[C@@H]1C1=C(C=C(C=C1OC)OC)OC)C LFBJHARYMYDANW-JIOHBXSKSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229950010817 alvocidib Drugs 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical class CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- KHMVXSQLPUNRCF-UHFFFAOYSA-N DL-Adalin Natural products C1CCC2CC(=O)CC1(CCCCC)N2 KHMVXSQLPUNRCF-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- LGMSNQNWOCSPIK-LWHGMNCYSA-N alvocidib hydrochloride Chemical compound Cl.O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O LGMSNQNWOCSPIK-LWHGMNCYSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007257 deesterification reaction Methods 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/04—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 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
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/42—Oxygen atoms attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19802449A DE19802449A1 (de) | 1998-01-23 | 1998-01-23 | Verfahren zur Herstellung von (-)cis-3-Hydroxy-1-methyl-4-(2,4,6-trimethoxypyhenyl)-piperidin |
| PCT/EP1998/008327 WO1999037615A1 (de) | 1998-01-23 | 1998-12-18 | Verfahren zur herstellung von (-)cis-3- hydroxy-1- methyl-4-(2, 4,6-trimethoxyphenyl)- piperidin |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20003454D0 NO20003454D0 (no) | 2000-07-04 |
| NO20003454L NO20003454L (no) | 2000-07-04 |
| NO321933B1 true NO321933B1 (no) | 2006-07-24 |
Family
ID=7855418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20003454A NO321933B1 (no) | 1998-01-23 | 2000-07-04 | Fremgangsmate for fremstilling av (-)cis-3-hydroksy-1-metyl-4-(2,4,6-trimetoksyfenyl)-piperidin og mellomprodukter. |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US6225473B1 (cs) |
| EP (1) | EP1049674B1 (cs) |
| JP (1) | JP4585116B2 (cs) |
| KR (1) | KR100567941B1 (cs) |
| CN (1) | CN1137096C (cs) |
| AR (1) | AR015218A1 (cs) |
| AT (1) | ATE355270T1 (cs) |
| AU (1) | AU762407B2 (cs) |
| BR (1) | BR9814774B1 (cs) |
| CA (1) | CA2318946C (cs) |
| CY (1) | CY1106511T1 (cs) |
| CZ (1) | CZ298852B6 (cs) |
| DE (2) | DE19802449A1 (cs) |
| DK (1) | DK1049674T3 (cs) |
| ES (1) | ES2281943T3 (cs) |
| HU (1) | HU227928B1 (cs) |
| IL (1) | IL137422A (cs) |
| NO (1) | NO321933B1 (cs) |
| NZ (1) | NZ505897A (cs) |
| PL (1) | PL190790B1 (cs) |
| PT (1) | PT1049674E (cs) |
| RU (1) | RU2265595C2 (cs) |
| SK (1) | SK285883B6 (cs) |
| TR (1) | TR200002146T2 (cs) |
| WO (1) | WO1999037615A1 (cs) |
| ZA (1) | ZA99477B (cs) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6437136B2 (en) * | 1998-01-23 | 2002-08-20 | Aventis Pharma Deutschland Gmbh | Process for the preparation of (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine |
| DE19809649A1 (de) * | 1998-03-06 | 1999-09-09 | Hoechst Marion Roussel De Gmbh | Verfahren zur enzymatischen Enantiomeren-Trennung von 3(R)- und 3(S)-Hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridin bzw. der Carbonsäureester |
| EP3286564A1 (en) | 2015-04-20 | 2018-02-28 | Tolero Pharmaceuticals, Inc. | Predicting response to alvocidib by mitochondrial profiling |
| TR201911032T4 (tr) | 2015-05-18 | 2019-08-21 | Tolero Pharmaceuticals Inc | Artırılmış biyoyararlanıma sahip alvocıdıb ön ilaçları. |
| CN108289861B (zh) | 2015-08-03 | 2021-11-02 | 大日本住友制药肿瘤公司 | 用于治疗癌症的组合疗法 |
| US11279694B2 (en) | 2016-11-18 | 2022-03-22 | Sumitomo Dainippon Pharma Oncology, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
| US10132797B2 (en) | 2016-12-19 | 2018-11-20 | Tolero Pharmaceuticals, Inc. | Profiling peptides and methods for sensitivity profiling |
| WO2019055579A1 (en) | 2017-09-12 | 2019-03-21 | Tolero Pharmaceuticals, Inc. | TREATMENT REGIME FOR CANCERS THAT ARE INSENSITIVE TO BCL-2 INHIBITORS USING THE MCL-1 ALVOCIDIB INHIBITOR |
| EP3890749B1 (en) | 2018-12-04 | 2025-10-29 | Sumitomo Pharma America, Inc. | Cdk9 inhibitors and polymorphs thereof for use as agents for treatment of cancer |
| WO2020191326A1 (en) | 2019-03-20 | 2020-09-24 | Sumitomo Dainippon Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (aml) with venetoclax failure |
| CN110577974B (zh) * | 2019-09-10 | 2021-07-20 | 杭州澳赛诺生物科技有限公司 | 手性3-羟基-1,2,3,6-四氢吡啶的合成方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN164232B (cs) * | 1986-04-11 | 1989-02-04 | Hoechst India | |
| US5284856A (en) * | 1988-10-28 | 1994-02-08 | Hoechst Aktiengesellschaft | Oncogene-encoded kinases inhibition using 4-H-1-benzopyran-4-one derivatives |
| DE3836676A1 (de) * | 1988-10-28 | 1990-05-03 | Hoechst Ag | Die verwendung von 4h-1-benzopyran-4-on-derivaten, neue 4h-1-benzopyran-4-on-derivate und diese enthaltende arzneimittel |
| US5849733A (en) * | 1996-05-10 | 1998-12-15 | Bristol-Myers Squibb Co. | 2-thio or 2-oxo flavopiridol analogs |
| US5908934A (en) * | 1996-09-26 | 1999-06-01 | Bristol-Myers Squibb Company | Process for the preparation of chiral ketone intermediates useful for the preparation of flavopiridol and analogs |
-
1998
- 1998-01-23 DE DE19802449A patent/DE19802449A1/de not_active Withdrawn
- 1998-12-18 PT PT98966836T patent/PT1049674E/pt unknown
- 1998-12-18 CA CA002318946A patent/CA2318946C/en not_active Expired - Lifetime
- 1998-12-18 US US09/600,775 patent/US6225473B1/en not_active Expired - Lifetime
- 1998-12-18 TR TR2000/02146T patent/TR200002146T2/xx unknown
- 1998-12-18 CZ CZ20002665A patent/CZ298852B6/cs not_active IP Right Cessation
- 1998-12-18 EP EP98966836A patent/EP1049674B1/de not_active Expired - Lifetime
- 1998-12-18 AU AU25135/99A patent/AU762407B2/en not_active Expired
- 1998-12-18 KR KR1020007007959A patent/KR100567941B1/ko not_active Expired - Lifetime
- 1998-12-18 WO PCT/EP1998/008327 patent/WO1999037615A1/de not_active Ceased
- 1998-12-18 RU RU2000122151/04A patent/RU2265595C2/ru active
- 1998-12-18 JP JP2000528539A patent/JP4585116B2/ja not_active Expired - Lifetime
- 1998-12-18 SK SK1097-2000A patent/SK285883B6/sk not_active IP Right Cessation
- 1998-12-18 CN CNB988132311A patent/CN1137096C/zh not_active Expired - Lifetime
- 1998-12-18 DE DE59813924T patent/DE59813924D1/de not_active Expired - Lifetime
- 1998-12-18 IL IL13742298A patent/IL137422A/xx not_active IP Right Cessation
- 1998-12-18 ES ES98966836T patent/ES2281943T3/es not_active Expired - Lifetime
- 1998-12-18 DK DK98966836T patent/DK1049674T3/da active
- 1998-12-18 PL PL342064A patent/PL190790B1/pl unknown
- 1998-12-18 AT AT98966836T patent/ATE355270T1/de active
- 1998-12-18 NZ NZ505897A patent/NZ505897A/xx not_active IP Right Cessation
- 1998-12-18 BR BRPI9814774-9A patent/BR9814774B1/pt not_active IP Right Cessation
- 1998-12-18 HU HU0100649A patent/HU227928B1/hu unknown
-
1999
- 1999-01-21 AR ARP990100242A patent/AR015218A1/es active IP Right Grant
- 1999-01-22 ZA ZA9900477A patent/ZA99477B/xx unknown
-
2000
- 2000-07-04 NO NO20003454A patent/NO321933B1/no not_active IP Right Cessation
-
2007
- 2007-04-12 CY CY20071100513T patent/CY1106511T1/el unknown
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| MK1K | Patent expired |