NO174469B - Analogifremgangsmaate for fremstilling av terapeutisk aktive N- amino-karbamater - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive N- amino-karbamater Download PDFInfo
- Publication number
- NO174469B NO174469B NO904209A NO904209A NO174469B NO 174469 B NO174469 B NO 174469B NO 904209 A NO904209 A NO 904209A NO 904209 A NO904209 A NO 904209A NO 174469 B NO174469 B NO 174469B
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- preparation
- therapeutically active
- cis
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 9
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 18
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 102100033639 Acetylcholinesterase Human genes 0.000 description 13
- 108010022752 Acetylcholinesterase Proteins 0.000 description 13
- 229940022698 acetylcholinesterase Drugs 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 102000003914 Cholinesterases Human genes 0.000 description 5
- 108090000322 Cholinesterases Proteins 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- HKGWQUVGHPDEBZ-OLZOCXBDSA-N eseroline Chemical compound C1=C(O)C=C2[C@]3(C)CCN(C)[C@@H]3N(C)C2=C1 HKGWQUVGHPDEBZ-OLZOCXBDSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 229940048961 cholinesterase Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000030214 innervation Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- 229940124596 AChE inhibitor Drugs 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 229960001697 physostigmine Drugs 0.000 description 2
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- VOWHONRMOCHCGC-UHFFFAOYSA-N 1,2,3,3a,4,8b-hexahydropyrrolo[2,3-b]indole Chemical group C1=CC=C2C3CCNC3NC2=C1 VOWHONRMOCHCGC-UHFFFAOYSA-N 0.000 description 1
- GZYVLKKMMDFCKR-UHFFFAOYSA-M 2-acetylsulfanylethyl(trimethyl)azanium;chloride Chemical compound [Cl-].CC(=O)SCC[N+](C)(C)C GZYVLKKMMDFCKR-UHFFFAOYSA-M 0.000 description 1
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010021333 Ileus paralytic Diseases 0.000 description 1
- 201000005081 Intestinal Pseudo-Obstruction Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- -1 hydrazine compound Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007074 memory dysfunction Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 201000007620 paralytic ileus Diseases 0.000 description 1
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cephalosporin Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/413,901 US4914102A (en) | 1989-09-28 | 1989-09-28 | N-aminocarbamates related to physostigmine, pharmacentical compositions and use |
| US07/431,103 US5081117A (en) | 1989-09-28 | 1989-11-03 | 4- and 6-carbamates related to physostigmine and intermediates for the preparation thereof |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO904209D0 NO904209D0 (no) | 1990-09-27 |
| NO904209L NO904209L (no) | 1991-04-02 |
| NO174469B true NO174469B (no) | 1994-01-31 |
| NO174469C NO174469C (ko) | 1994-05-18 |
Family
ID=40149690
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO904209A NO174469B (no) | 1989-09-28 | 1990-09-27 | Analogifremgangsmaate for fremstilling av terapeutisk aktive N- amino-karbamater |
| NO904783A NO175980C (no) | 1989-09-28 | 1990-11-02 | Analogifremgangsmåte for fremstilling av terapeutisk aktive 4- og 6-karbamater av physostigmin og mellomprodukter |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO904783A NO175980C (no) | 1989-09-28 | 1990-11-02 | Analogifremgangsmåte for fremstilling av terapeutisk aktive 4- og 6-karbamater av physostigmin og mellomprodukter |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US4914102A (ko) |
| EP (2) | EP0420140B1 (ko) |
| JP (2) | JPH0723377B2 (ko) |
| KR (1) | KR100189665B1 (ko) |
| AT (2) | ATE156825T1 (ko) |
| AU (3) | AU639943B2 (ko) |
| CA (2) | CA2026381A1 (ko) |
| CZ (1) | CZ279604B6 (ko) |
| DE (2) | DE69031259T2 (ko) |
| DK (2) | DK0420140T3 (ko) |
| ES (2) | ES2104572T3 (ko) |
| FI (2) | FI93961C (ko) |
| GR (2) | GR3019468T3 (ko) |
| HU (1) | HU206355B (ko) |
| IE (1) | IE72153B1 (ko) |
| IL (2) | IL95807A (ko) |
| NO (2) | NO174469B (ko) |
| NZ (2) | NZ235460A (ko) |
| PL (1) | PL287618A1 (ko) |
| PT (2) | PT95449B (ko) |
| ZA (2) | ZA907725B (ko) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4791107A (en) * | 1986-07-16 | 1988-12-13 | Hoechst-Roussel Pharmaceuticals, Inc. | Memory enhancing and analgesic 1,2,3,3A,8,8A-hexahydro-3A,8 (and) 1,3A,8)-di(and tri)methylpyrrolo(2,3-B)indoles, compositions and use |
| US4971992A (en) * | 1989-03-27 | 1990-11-20 | Hoechst-Roussel Pharmaceuticals Inc. | Carbonate derivatives of eseroline |
| ATE125254T1 (de) * | 1989-09-19 | 1995-08-15 | Hoechst Roussel Pharma | Verfahren zur racematspaltung von 5-alkoxy- substituierten (+/-)-1,3- dimethyloxindolylethylaminen. |
| US4914102A (en) * | 1989-09-28 | 1990-04-03 | Hoechst Roussel Pharmaceuticals, Inc. | N-aminocarbamates related to physostigmine, pharmacentical compositions and use |
| US5077289A (en) * | 1989-11-30 | 1991-12-31 | Hoechst Roussel Pharmaceuticals Inc. | Memory enhancing and analgesic aminocarbonylcarbamates related to physostigmine |
| EP0438796B1 (en) * | 1990-01-22 | 1998-08-26 | HOECHST MARION ROUSSEL, Inc. | Process for the enantioselection synthesis of alkylated oxindoles used as intermediates in the preparation of physostigmine |
| MC2287A1 (fr) * | 1990-06-27 | 1993-07-14 | Hoechst Roussel Pharma | Tetrahydroisoquinoleinylcarbamates de 1,2,3,3a,8,8a-hexahydro-1,31,8-trimethylpyrrolo(2,3,-b)indole |
| US5171750A (en) * | 1991-09-26 | 1992-12-15 | The United States Of America As Represented By The Department Of Health And Human Services | Substituted phenserines as specific inhibitors of acetylcholinesterase |
| DE69233093T2 (de) * | 1991-09-26 | 2003-12-18 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Washington | Substituierte phenserine und phenylcarbamate von (-)-eserolin, (-)-n1-noreserolin und (-)-n1-benzylnoresorolin als spezifische acetylcholinesterase-inhibitoren |
| US5153193A (en) * | 1991-10-01 | 1992-10-06 | Hoechst-Roussel Pharmaceuticals Incorporated | Carbamate derivatives of 4-amino-3-isoxazolidinones, 3-amino-1-hydroxypyrrolidin-2-ones and 1-amino-1-cyclopropanecarboxylic acid analogs |
| IT1253007B (it) * | 1991-12-31 | 1995-07-10 | Aesculapius Farma Srl | Derivati dell'eserolina ad attivita' anticolinesterasica,procedimento per la loro preparazione e composizioni farmaceutiche che li contengono |
| FI933264A (fi) * | 1992-07-21 | 1994-01-22 | Hoechst Roussel Pharma | Foerfarande foer framstaellning av fysostigminkarbamatderivat fraon fysostigmin |
| US5302721A (en) * | 1992-07-21 | 1994-04-12 | Hoechst-Roussel Pharmaceuticals Incorporated | Method of preparation of physostigmine carbamate derivatives from eseretholes |
| US5409948A (en) * | 1992-11-23 | 1995-04-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method for treating cognitive disorders with phenserine |
| US5665880A (en) * | 1996-10-31 | 1997-09-09 | Hoechst Marion Roussel, Inc. | Method of preparation of physostigmine carbamate derivatives from eseretholes |
| US5677457A (en) * | 1996-12-19 | 1997-10-14 | Hoechst Marion Roussel, Inc. | Method of preparation of physostigmine carbamate derivatives from eseroline ethers |
| US6218383B1 (en) | 1998-08-07 | 2001-04-17 | Targacept, Inc. | Pharmaceutical compositions for the prevention and treatment of central nervous system disorders |
| SI2389937T1 (sl) * | 2002-06-14 | 2018-10-30 | Toyama Chemical Co., Ltd, | Farmacevtska sestava za izboljšanje možganske funkcije |
| WO2005042475A2 (en) * | 2003-10-21 | 2005-05-12 | Sention, Inc. | Carbamoyl esters that inhibit cholinesterase and release pharmacologically active agents |
| US20050222123A1 (en) | 2004-01-27 | 2005-10-06 | North Shore-Long Island Jewish Research Institute | Cholinesterase inhibitors for treating inflammation |
| US20050182044A1 (en) * | 2004-02-17 | 2005-08-18 | Bruinsma Gosse B. | Combinatorial therapy with an acetylcholinesterase inhibitor and (3aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3,-b]indol-5-yl phenylcarbamate |
| CA2508585A1 (en) * | 2004-06-01 | 2005-12-01 | Axonyx, Inc. | Transdermal delivery system for treatment of cognitive disorders |
| EP1604686A1 (en) * | 2004-06-08 | 2005-12-14 | Axonyx, Inc. | Use of phenserine and a HMG CoA reductase inhibitor for delaying Alzheimer's disease progression |
| WO2006060082A1 (en) * | 2004-10-22 | 2006-06-08 | THE GOVERNMENT OF THE U.S.A. as represented by THE SEC., DEPT. OF HEALTH & HUMAN SERVICES, NATIONAL INSTITUTES OF HEALTH | Tricyclic compounds, preparation thereof and use thereof as cholinesterase activity inhibitors |
| WO2011100373A1 (en) * | 2010-02-09 | 2011-08-18 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| MX362886B (es) | 2012-12-13 | 2019-02-22 | H Lundbeck As | Composición sinérgica que comprende vortioxetina y donepezilo para incrementar los niveles de acetilcolina en el cerebro, y el uso de la misma en el tratamiento de una disfunción cognitiva. |
| EP3827820A1 (en) | 2013-03-15 | 2021-06-02 | The Johns Hopkins University | Brivaracetam for improving cognitive function |
| JP6433482B2 (ja) | 2013-03-15 | 2018-12-05 | エージンバイオ， インコーポレイテッド | 認知機能を改善するための方法および組成物 |
| WO2016191288A1 (en) | 2015-05-22 | 2016-12-01 | Agenebio, Inc. | Extended release pharmaceutical compositions of levetiracetam |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3897451A (en) * | 1973-04-27 | 1975-07-29 | Univ Ohio State Res Found | Synthesis of oxindoles from anilines and intermediates therein |
| IT1109003B (it) * | 1977-09-20 | 1985-12-16 | Univ Firenze | Derivati dell 1 2 3 8 3 a 8 a esai dropirrolo 23 b indolo |
| IT1199076B (it) * | 1984-03-01 | 1988-12-30 | Consiglio Nazionale Ricerche | Derivati della fisostigmina con proprieta'di inibizione della aceticolinesterasi e relativo procedimento di produzione |
| US4760083A (en) * | 1986-04-10 | 1988-07-26 | E. I. Dupont De Nemours & Company | 3,3-disubstituted indolines |
| US4791107A (en) * | 1986-07-16 | 1988-12-13 | Hoechst-Roussel Pharmaceuticals, Inc. | Memory enhancing and analgesic 1,2,3,3A,8,8A-hexahydro-3A,8 (and) 1,3A,8)-di(and tri)methylpyrrolo(2,3-B)indoles, compositions and use |
| IT1225462B (it) * | 1987-04-03 | 1990-11-14 | Mediolanum Farmaceutici Srl | Sali organici di derivati della fisostigmina |
| US4741107A (en) * | 1987-07-31 | 1988-05-03 | Circle Jeffrey L | Artwork aid adapted for facilitating placement of lettering along arc of a circle |
| US4971992A (en) * | 1989-03-27 | 1990-11-20 | Hoechst-Roussel Pharmaceuticals Inc. | Carbonate derivatives of eseroline |
| US5006537A (en) * | 1989-08-02 | 1991-04-09 | Hoechst-Roussel Pharmaceuticals, Inc. | 1,3-dihydro-1-(pyridinylamino)-2H-indol-2-ones |
| ATE125254T1 (de) * | 1989-09-19 | 1995-08-15 | Hoechst Roussel Pharma | Verfahren zur racematspaltung von 5-alkoxy- substituierten (+/-)-1,3- dimethyloxindolylethylaminen. |
| US4914102A (en) * | 1989-09-28 | 1990-04-03 | Hoechst Roussel Pharmaceuticals, Inc. | N-aminocarbamates related to physostigmine, pharmacentical compositions and use |
| US5077289A (en) * | 1989-11-30 | 1991-12-31 | Hoechst Roussel Pharmaceuticals Inc. | Memory enhancing and analgesic aminocarbonylcarbamates related to physostigmine |
| EP0438796B1 (en) * | 1990-01-22 | 1998-08-26 | HOECHST MARION ROUSSEL, Inc. | Process for the enantioselection synthesis of alkylated oxindoles used as intermediates in the preparation of physostigmine |
-
1989
- 1989-09-28 US US07/413,901 patent/US4914102A/en not_active Expired - Fee Related
- 1989-11-03 US US07/431,103 patent/US5081117A/en not_active Expired - Fee Related
-
1990
- 1990-09-25 EP EP90118376A patent/EP0420140B1/en not_active Expired - Lifetime
- 1990-09-25 DK DK90118376.4T patent/DK0420140T3/da active
- 1990-09-25 DE DE69031259T patent/DE69031259T2/de not_active Expired - Fee Related
- 1990-09-25 AT AT90118376T patent/ATE156825T1/de not_active IP Right Cessation
- 1990-09-25 ES ES90118376T patent/ES2104572T3/es not_active Expired - Lifetime
- 1990-09-26 NZ NZ235460A patent/NZ235460A/xx unknown
- 1990-09-26 FI FI904730A patent/FI93961C/fi not_active IP Right Cessation
- 1990-09-26 IL IL9580790A patent/IL95807A/en not_active IP Right Cessation
- 1990-09-27 JP JP2255477A patent/JPH0723377B2/ja not_active Expired - Lifetime
- 1990-09-27 PT PT95449A patent/PT95449B/pt not_active IP Right Cessation
- 1990-09-27 CA CA002026381A patent/CA2026381A1/en not_active Abandoned
- 1990-09-27 ZA ZA907725A patent/ZA907725B/xx unknown
- 1990-09-27 AU AU63227/90A patent/AU639943B2/en not_active Ceased
- 1990-09-27 NO NO904209A patent/NO174469B/no not_active IP Right Cessation
- 1990-11-01 NZ NZ235921A patent/NZ235921A/en unknown
- 1990-11-01 IL IL9620990A patent/IL96209A/en not_active IP Right Cessation
- 1990-11-01 FI FI905418A patent/FI92701C/fi not_active IP Right Cessation
- 1990-11-01 KR KR1019900017657A patent/KR100189665B1/ko not_active IP Right Cessation
- 1990-11-02 HU HU906999A patent/HU206355B/hu not_active IP Right Cessation
- 1990-11-02 IE IE396590A patent/IE72153B1/en not_active IP Right Cessation
- 1990-11-02 PL PL28761890A patent/PL287618A1/xx unknown
- 1990-11-02 CZ CS905407A patent/CZ279604B6/cs not_active IP Right Cessation
- 1990-11-02 AU AU65712/90A patent/AU635575B2/en not_active Ceased
- 1990-11-02 ZA ZA908800A patent/ZA908800B/xx unknown
- 1990-11-02 CA CA002029265A patent/CA2029265C/en not_active Expired - Fee Related
- 1990-11-02 NO NO904783A patent/NO175980C/no not_active IP Right Cessation
- 1990-11-02 PT PT95772A patent/PT95772B/pt not_active IP Right Cessation
- 1990-11-02 JP JP2295595A patent/JPH0780885B2/ja not_active Expired - Fee Related
- 1990-11-07 DK DK90121267.0T patent/DK0484573T3/da active
- 1990-11-07 ES ES90121267T patent/ES2085309T3/es not_active Expired - Lifetime
- 1990-11-07 AT AT90121267T patent/ATE135355T1/de not_active IP Right Cessation
- 1990-11-07 DE DE69025941T patent/DE69025941T2/de not_active Expired - Fee Related
- 1990-11-07 EP EP90121267A patent/EP0484573B1/en not_active Expired - Lifetime
-
1993
- 1993-01-27 AU AU32046/93A patent/AU646986B2/en not_active Ceased
-
1996
- 1996-03-29 GR GR960400847T patent/GR3019468T3/el unknown
-
1997
- 1997-10-14 GR GR970402666T patent/GR3025021T3/el unknown
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