IL95807A - N-aminocarbamates related to physostigmine, a process for their preparation and their use in pharmaceutical compositions - Google Patents
N-aminocarbamates related to physostigmine, a process for their preparation and their use in pharmaceutical compositionsInfo
- Publication number
- IL95807A IL95807A IL9580790A IL9580790A IL95807A IL 95807 A IL95807 A IL 95807A IL 9580790 A IL9580790 A IL 9580790A IL 9580790 A IL9580790 A IL 9580790A IL 95807 A IL95807 A IL 95807A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- cis
- hydrogen
- loweralkyl
- formula
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 3
- 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 title abstract description 6
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 title description 5
- 229960001697 physostigmine Drugs 0.000 title description 5
- OWIUPIRUAQMTTK-UHFFFAOYSA-N carbazic acid Chemical class NNC(O)=O OWIUPIRUAQMTTK-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 38
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
- 230000007074 memory dysfunction Effects 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 9
- -1 loweralkyl Chemical group 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- NCJATRNFAUVTSN-UHFFFAOYSA-N 1H-indol-5-yl N-piperidin-1-ylcarbamate Chemical compound N1(CCCCC1)NC(OC=1C=C2C=CNC2=CC=1)=O NCJATRNFAUVTSN-UHFFFAOYSA-N 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- DLUOKQGJGMSAHA-UHFFFAOYSA-N morpholin-4-ylcarbamic acid Chemical compound OC(=O)NN1CCOCC1 DLUOKQGJGMSAHA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 230000001713 cholinergic effect Effects 0.000 abstract description 4
- 230000006735 deficit Effects 0.000 abstract description 2
- 102100033639 Acetylcholinesterase Human genes 0.000 description 14
- 108010022752 Acetylcholinesterase Proteins 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 229940022698 acetylcholinesterase Drugs 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 239000000872 buffer Substances 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
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- 238000006243 chemical reaction Methods 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000003914 Cholinesterases Human genes 0.000 description 4
- 108090000322 Cholinesterases Proteins 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 229940079593 drug 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
- 239000003112 inhibitor Substances 0.000 description 4
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- 210000001519 tissue Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229910001868 water Inorganic materials 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-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
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
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- 239000013078 crystal Substances 0.000 description 3
- 230000030214 innervation Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000012360 testing method Methods 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
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 238000002835 absorbance Methods 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
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 229940048961 cholinesterase Drugs 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
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- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
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- TTYZALKMLFBJIE-UHFFFAOYSA-N (3,4,8b-trimethyl-2,3a,6,7,8,8a-hexahydro-1H-pyrrolo[2,3-b]indol-7-yl) N-morpholin-4-ylcarbamate Chemical compound N1(CCOCC1)NC(OC1CC2C3(C(N(C2=CC1)C)N(CC3)C)C)=O TTYZALKMLFBJIE-UHFFFAOYSA-N 0.000 description 1
- LKPOSIGVMHFFGJ-UHFFFAOYSA-N (3,4,8b-trimethyl-2,3a,6,7,8,8a-hexahydro-1H-pyrrolo[2,3-b]indol-7-yl) N-piperidin-1-ylcarbamate Chemical compound N1(CCCCC1)NC(OC1CC2C3(C(N(C2=CC1)C)N(CC3)C)C)=O LKPOSIGVMHFFGJ-UHFFFAOYSA-N 0.000 description 1
- POJYSQCMDUIYSB-UHFFFAOYSA-N (anilinoazaniumyl)formate Chemical compound OC(=O)NNC1=CC=CC=C1 POJYSQCMDUIYSB-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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- XVSNDUPHGAKGNG-UHFFFAOYSA-N C1(CCCCC1)NNC(=O)OC=1C=C2C=CNC2=CC1 Chemical compound C1(CCCCC1)NNC(=O)OC=1C=C2C=CNC2=CC1 XVSNDUPHGAKGNG-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
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- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 150000003444 succinic acids Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (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)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (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 (2)
| Publication Number | Publication Date |
|---|---|
| IL95807A0 IL95807A0 (en) | 1991-06-30 |
| IL95807A true IL95807A (en) | 1994-10-21 |
Family
ID=40149690
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9580790A IL95807A (en) | 1989-09-28 | 1990-09-26 | N-aminocarbamates related to physostigmine, a process for their preparation and their use in pharmaceutical compositions |
| IL9620990A IL96209A (en) | 1989-09-28 | 1990-11-01 | 4- and 6-carbamates related to physostigmine a process for their preparation and their use as medicaments |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9620990A IL96209A (en) | 1989-09-28 | 1990-11-01 | 4- and 6-carbamates related to physostigmine a process for their preparation and their use as medicaments |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US4914102A (cs) |
| EP (2) | EP0420140B1 (cs) |
| JP (2) | JPH0723377B2 (cs) |
| KR (1) | KR100189665B1 (cs) |
| AT (2) | ATE156825T1 (cs) |
| AU (3) | AU639943B2 (cs) |
| CA (2) | CA2026381A1 (cs) |
| CZ (1) | CZ279604B6 (cs) |
| DE (2) | DE69031259T2 (cs) |
| DK (2) | DK0420140T3 (cs) |
| ES (2) | ES2104572T3 (cs) |
| FI (2) | FI93961C (cs) |
| GR (2) | GR3019468T3 (cs) |
| HU (1) | HU206355B (cs) |
| IE (1) | IE72153B1 (cs) |
| IL (2) | IL95807A (cs) |
| NO (2) | NO174469B (cs) |
| NZ (2) | NZ235460A (cs) |
| PL (1) | PL287618A1 (cs) |
| PT (2) | PT95449B (cs) |
| ZA (2) | ZA907725B (cs) |
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 |
| ES2113859T3 (es) * | 1990-06-27 | 1998-05-16 | Hoechst Marion Roussel Inc | Tetrahidroisoquinolinilcarbamatos de 1,2,3,3a,8,8a-hexahidro-1,3a,8-trimetilpirrolo(2,3-b)indol. |
| 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 |
| EP0606366B1 (en) * | 1991-09-26 | 2003-06-04 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY of the DEPARTMENT OF HEALTH AND HUMAN SERVICES | Substituted phenserines and phenylcarbamates of (-)-eseroline, (-)-n1-noreseroline, and (-)-n1-benzylnoreseroline; as specific inhibitors of acetylcholinesterase |
| 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 |
| FI933264A7 (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 |
| US7342043B2 (en) * | 2002-06-14 | 2008-03-11 | Toyama Chemical Co., Ltd. | Medicinal compositions improving brain function and method for improving brain function |
| EP2314571A3 (en) * | 2003-10-21 | 2011-08-31 | CoLucid Pharmaceuticals, 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 |
| JP2005350471A (ja) * | 2004-06-08 | 2005-12-22 | Axonyx Inc | β−アミロイド前駆体タンパク質阻害剤およびＨＭＧＣｏＡ還元酵素阻害剤を使用するアルツハイマー病の進行を遅延させる方法 |
| 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 |
| CN102905532A (zh) * | 2010-02-09 | 2013-01-30 | 约翰斯.霍普金斯大学 | 用于改善认知功能的方法和组合物 |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| KR102171152B1 (ko) | 2012-12-13 | 2020-10-29 | 하. 룬드벡 아크티에셀스카브 | 보르티옥세틴 및 도네페질을 포함하는 조성물 |
| HK1218623A1 (zh) | 2013-03-15 | 2017-03-03 | 艾吉因生物股份有限公司 | 用於改善認知功能的方法和組合物 |
| WO2014144663A1 (en) | 2013-03-15 | 2014-09-18 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| JP6899043B2 (ja) | 2015-05-22 | 2021-07-07 | エージンバイオ， インコーポレイテッド | レベチラセタムの持続放出性医薬組成物 |
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 AT AT90118376T patent/ATE156825T1/de not_active IP Right Cessation
- 1990-09-25 DK DK90118376.4T patent/DK0420140T3/da active
- 1990-09-25 ES ES90118376T patent/ES2104572T3/es not_active Expired - Lifetime
- 1990-09-25 EP EP90118376A patent/EP0420140B1/en not_active Expired - Lifetime
- 1990-09-25 DE DE69031259T patent/DE69031259T2/de not_active Expired - Fee Related
- 1990-09-26 FI FI904730A patent/FI93961C/fi not_active IP Right Cessation
- 1990-09-26 NZ NZ235460A patent/NZ235460A/xx unknown
- 1990-09-26 IL IL9580790A patent/IL95807A/en not_active IP Right Cessation
- 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
- 1990-09-27 CA CA002026381A patent/CA2026381A1/en not_active Abandoned
- 1990-09-27 PT PT95449A patent/PT95449B/pt not_active IP Right Cessation
- 1990-09-27 JP JP2255477A patent/JPH0723377B2/ja not_active Expired - Lifetime
- 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 Expired - Fee Related
- 1990-11-02 PL PL28761890A patent/PL287618A1/xx unknown
- 1990-11-02 JP JP2295595A patent/JPH0780885B2/ja not_active Expired - Fee Related
- 1990-11-02 NO NO904783A patent/NO175980C/no not_active IP Right Cessation
- 1990-11-02 CA CA002029265A patent/CA2029265C/en not_active Expired - Fee Related
- 1990-11-02 ZA ZA908800A patent/ZA908800B/xx unknown
- 1990-11-02 AU AU65712/90A patent/AU635575B2/en not_active Ceased
- 1990-11-02 IE IE396590A patent/IE72153B1/en not_active IP Right Cessation
- 1990-11-02 PT PT95772A patent/PT95772B/pt not_active IP Right Cessation
- 1990-11-02 HU HU906999A patent/HU206355B/hu not_active IP Right Cessation
- 1990-11-02 CZ CS905407A patent/CZ279604B6/cs 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
- 1990-11-07 AT AT90121267T patent/ATE135355T1/de not_active IP Right Cessation
- 1990-11-07 DK DK90121267.0T patent/DK0484573T3/da active
- 1990-11-07 ES ES90121267T patent/ES2085309T3/es 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
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| KB | Patent renewed | ||
| HC | Change of name of proprietor(s) | ||
| RH | Patent void |