NO301276B1 - Fremgangsmåte for fremstilling av fysostigminkarbamatderivater fra fysostigmin - Google Patents
Fremgangsmåte for fremstilling av fysostigminkarbamatderivater fra fysostigmin Download PDFInfo
- Publication number
- NO301276B1 NO301276B1 NO932616A NO932616A NO301276B1 NO 301276 B1 NO301276 B1 NO 301276B1 NO 932616 A NO932616 A NO 932616A NO 932616 A NO932616 A NO 932616A NO 301276 B1 NO301276 B1 NO 301276B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- lower alkyl
- physostigmine
- equiv
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 19
- 238000002360 preparation method Methods 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 description 45
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 title description 33
- 229960001697 physostigmine Drugs 0.000 title description 33
- -1 physostigmine carbamate derivatives Chemical class 0.000 title description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 30
- 150000001875 compounds Chemical class 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 239000011541 reaction mixture Substances 0.000 claims description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 239000012948 isocyanate Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 4
- 150000002513 isocyanates Chemical class 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000004703 alkoxides Chemical class 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 3
- 239000012429 reaction media Substances 0.000 claims 2
- 239000007810 chemical reaction solvent Substances 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 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 41
- 239000000203 mixture Substances 0.000 description 39
- 238000004128 high performance liquid chromatography Methods 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 229960000583 acetic acid Drugs 0.000 description 20
- 239000012362 glacial acetic acid Substances 0.000 description 17
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 15
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000012071 phase Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- SHXGGYLLZCCNAX-UHFFFAOYSA-N (3-chlorophenyl) carbamate Chemical class NC(=O)OC1=CC=CC(Cl)=C1 SHXGGYLLZCCNAX-UHFFFAOYSA-N 0.000 description 4
- AUELWJRRASQDKI-UHFFFAOYSA-N cyclohexyl carbamate Chemical class NC(=O)OC1CCCCC1 AUELWJRRASQDKI-UHFFFAOYSA-N 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000011097 chromatography purification Methods 0.000 description 3
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 3
- IIFRKALDATVOJE-GGAORHGYSA-N quilostigmine Chemical compound C1CC2=CC=CC=C2CN1C(=O)OC(C=C12)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C IIFRKALDATVOJE-GGAORHGYSA-N 0.000 description 3
- HHIRBXHEYVDUAM-UHFFFAOYSA-N 1-chloro-3-isocyanatobenzene Chemical compound ClC1=CC=CC(N=C=O)=C1 HHIRBXHEYVDUAM-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 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
- 150000001412 amines Chemical class 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- HZOTZTANVBDFOF-PBCQUBLHSA-N physostigmine salicylate Chemical compound OC(=O)C1=CC=CC=C1O.C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C HZOTZTANVBDFOF-PBCQUBLHSA-N 0.000 description 2
- 229960002516 physostigmine salicylate Drugs 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- HLRAZPBRONOBEX-UHFFFAOYSA-N 1-phenylethyl carbamate Chemical compound NC(=O)OC(C)C1=CC=CC=C1 HLRAZPBRONOBEX-UHFFFAOYSA-N 0.000 description 1
- GRFUMPFWJKGLQC-UHFFFAOYSA-N 1-phenylethylcarbamic acid Chemical compound OC(=O)NC(C)C1=CC=CC=C1 GRFUMPFWJKGLQC-UHFFFAOYSA-N 0.000 description 1
- LJMGUXGFWFGHFH-UHFFFAOYSA-N 1h-indol-5-yl 3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1CC2=CC=CC=C2CN1C(=O)OC1=CC=C(NC=C2)C2=C1 LJMGUXGFWFGHFH-UHFFFAOYSA-N 0.000 description 1
- LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical compound OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- JJSCUXAFAJEQGB-MRVPVSSYSA-N [(1r)-1-isocyanatoethyl]benzene Chemical compound O=C=N[C@H](C)C1=CC=CC=C1 JJSCUXAFAJEQGB-MRVPVSSYSA-N 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000002252 carbamoylating effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 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 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate group Chemical group [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003695 memory enhancer Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
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)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cephalosporin Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US91871992A | 1992-07-21 | 1992-07-21 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO932616D0 NO932616D0 (no) | 1993-07-20 |
| NO932616L NO932616L (no) | 1994-01-24 |
| NO301276B1 true NO301276B1 (no) | 1997-10-06 |
Family
ID=25440831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO932616A NO301276B1 (no) | 1992-07-21 | 1993-07-20 | Fremgangsmåte for fremstilling av fysostigminkarbamatderivater fra fysostigmin |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US5498726A (fi) |
| JP (2) | JP2899502B2 (fi) |
| KR (1) | KR940005629A (fi) |
| CN (1) | CN1037443C (fi) |
| AU (1) | AU660550B2 (fi) |
| CA (1) | CA2100908A1 (fi) |
| CZ (1) | CZ284321B6 (fi) |
| FI (2) | FI933264A (fi) |
| HU (1) | HU212600B (fi) |
| IL (1) | IL106419A (fi) |
| MX (1) | MX9304397A (fi) |
| NO (1) | NO301276B1 (fi) |
| NZ (1) | NZ248180A (fi) |
| PH (1) | PH30885A (fi) |
| RU (1) | RU2116307C1 (fi) |
| TW (1) | TW239143B (fi) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5866120A (en) * | 1995-11-22 | 1999-02-02 | Advanced Corneal Systems, Inc. | Method for accelerating clearance of hemorrhagic blood from the vitreous humor with hyaluronidase |
| 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 |
| US6495700B1 (en) | 2002-01-09 | 2002-12-17 | Axonyx, Inc. | Process for producing phenserine and its analog |
| TWI294718B (en) | 2005-12-14 | 2008-03-11 | Ind Tech Res Inst | Frequency modulation-frequency shift keying (fm/fsk) demodulator |
Family Cites Families (5)
| 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 |
| IT1225462B (it) * | 1987-04-03 | 1990-11-14 | Mediolanum Farmaceutici Srl | Sali organici di derivati della fisostigmina |
| US4900748A (en) * | 1988-03-04 | 1990-02-13 | The United States Of America As Represented By The Department Of Health And Human Services | Carbamates related to (-)-physostigmine as cholinergic agents |
| 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 |
-
1993
- 1993-07-19 NZ NZ248180A patent/NZ248180A/en unknown
- 1993-07-19 PH PH46537A patent/PH30885A/en unknown
- 1993-07-19 FI FI933264A patent/FI933264A/fi unknown
- 1993-07-20 CA CA002100908A patent/CA2100908A1/en not_active Abandoned
- 1993-07-20 RU RU93045705A patent/RU2116307C1/ru active
- 1993-07-20 JP JP5179071A patent/JP2899502B2/ja not_active Expired - Lifetime
- 1993-07-20 NO NO932616A patent/NO301276B1/no not_active IP Right Cessation
- 1993-07-20 IL IL10641993A patent/IL106419A/en not_active IP Right Cessation
- 1993-07-20 AU AU42049/93A patent/AU660550B2/en not_active Ceased
- 1993-07-21 KR KR1019930013763A patent/KR940005629A/ko not_active Application Discontinuation
- 1993-07-21 CN CN93108583A patent/CN1037443C/zh not_active Expired - Fee Related
- 1993-07-21 TW TW082105785A patent/TW239143B/zh active
- 1993-07-21 CZ CZ931473A patent/CZ284321B6/cs not_active IP Right Cessation
- 1993-07-21 HU HU9302110A patent/HU212600B/hu not_active IP Right Cessation
- 1993-07-21 MX MX9304397A patent/MX9304397A/es not_active IP Right Cessation
-
1994
- 1994-03-22 US US08/216,238 patent/US5498726A/en not_active Expired - Fee Related
-
1997
- 1997-01-13 JP JP9003612A patent/JP2949085B2/ja not_active Expired - Lifetime
-
1999
- 1999-04-06 FI FI990752A patent/FI990752A/fi unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1037443C (zh) | 1998-02-18 |
| KR940005629A (ko) | 1994-03-22 |
| TW239143B (fi) | 1995-01-21 |
| AU660550B2 (en) | 1995-06-29 |
| CN1084174A (zh) | 1994-03-23 |
| CZ147393A3 (en) | 1994-03-16 |
| HU212600B (en) | 1996-09-30 |
| NZ248180A (en) | 1995-02-24 |
| JPH09176167A (ja) | 1997-07-08 |
| FI990752A0 (fi) | 1999-04-06 |
| JP2949085B2 (ja) | 1999-09-13 |
| PH30885A (en) | 1997-12-23 |
| NO932616D0 (no) | 1993-07-20 |
| JP2899502B2 (ja) | 1999-06-02 |
| AU4204993A (en) | 1994-01-27 |
| CZ284321B6 (cs) | 1998-10-14 |
| FI933264A (fi) | 1994-01-22 |
| CA2100908A1 (en) | 1994-01-22 |
| JPH06179678A (ja) | 1994-06-28 |
| NO932616L (no) | 1994-01-24 |
| RU2116307C1 (ru) | 1998-07-27 |
| FI990752A (fi) | 1999-04-06 |
| IL106419A0 (en) | 1993-11-15 |
| HUT65135A (en) | 1994-04-28 |
| HU9302110D0 (en) | 1993-11-29 |
| IL106419A (en) | 1999-12-31 |
| MX9304397A (es) | 1994-02-28 |
| US5498726A (en) | 1996-03-12 |
| FI933264A0 (fi) | 1993-07-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK283894B6 (sk) | Spôsob výroby 5-[2-etoxy-5-(4-metylpiperazin-1-ylsulfonyl)- fenyl]-1-metyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4,3-d]pyrimidin-7-ónu | |
| NO147914B (no) | Mellomprodukt ved fremstilling av farmakologisk aktive imidazol (1,5-a)(1,4)diazepinforbindelser | |
| US4347186A (en) | Process for preparing 5-aroyl 1,2-dihydro-3-H pyrrolo[1,2-a]pyrrole-1-carboxylic acids and novel intermediates therein | |
| NO301276B1 (no) | Fremgangsmåte for fremstilling av fysostigminkarbamatderivater fra fysostigmin | |
| US4703051A (en) | 4,7-dihydrothieno[2,3-B]pyridine derivatives useful in the treatment of cardiovascular diseases | |
| EP1299389B1 (en) | A process for preparing pyrazolopyrimidinone derivatives for the treatment of impotence | |
| US4458081A (en) | 5-Aroyl 1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-decarboxylates | |
| WO2010061398A1 (en) | Process for preparing dorzolamide hydrochloride and its intermediate | |
| US4565869A (en) | Dicarbamates | |
| AU2001258896A1 (en) | A process for preparing pyrazolopyrimidinone derivatives for the treatment of impotence | |
| EP0033214A2 (en) | Process for preparing therapeutically active triazoles | |
| US20020147190A1 (en) | Process for preparing 6-aryl-4H-S-triazolo[3,4-c]-thieno[2,3-e]-1,4-diazepines | |
| NO318781B1 (no) | Fremgangsmate til fremstilling av et 3(2H)-pyridazinon-4-substituert amino-5-klorderivat | |
| EP1091954B1 (en) | Process for producing (8-chloro-3,10-dibromo-6,11-dihydro-5h-benzo 5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidine | |
| CA2487672C (en) | Industrial process for preparing tropenol | |
| WO2006070387A1 (en) | PROCESS FOR PREPARING 5,6-DIHYDRO-4-(S)-(ETHYLAMINO)-6-(S) METHYL-4H-THIENO[2,3b]THIOPYRAN-2-SULPHONAMIDE-7,7-DIOXIDE HCI | |
| US6706883B1 (en) | Process for producing (8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-B]pyridin-11-YL)-1-piperdine | |
| KR100364226B1 (ko) | 7-할로-1-시클로프로필-6-플루오로-4-옥소-1,4-디히드로-[1.8]나프티리딘-3-카복실레이트의 제조방법 | |
| NO324982B1 (no) | Fremgangsmate for fremstilling av N-(5-(difenylfosfinoylmetyl)-4-(4-fluorfenyl)-6-isopropylpyrimidin-2-yl)-N-metylmetansulfonamid | |
| EA014934B1 (ru) | Способ получения оланзапина | |
| KR20240027729A (ko) | 이속사졸린카르복실산 유도체의 제조 방법 | |
| KR860001878B1 (ko) | 피라졸 유도체의 제법 | |
| NO174346B (no) | Fremgangsmaate for fremstilling av 5-aroyl-1,2-dihydro-3H-pyrrolo-(1,2- a)- pyrrol-1-carboxylsyrer og alkylestere og salter derav | |
| NO169228B (no) | 5-cyklopropyl-3-isocyanometyl-1,2,4-oksadiazol | |
| CA2410633A1 (en) | Aryloxy ester and acid compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |
Free format text: LAPSED IN JANUARY 2001 |