FI111461B - Menetelmä terapeuttisesti käyttökelpoisten silyloitujen asetyylikoliiniesteraasi-inhibiittorien valmistamiseksi - Google Patents
Menetelmä terapeuttisesti käyttökelpoisten silyloitujen asetyylikoliiniesteraasi-inhibiittorien valmistamiseksi Download PDFInfo
- Publication number
- FI111461B FI111461B FI953851A FI953851A FI111461B FI 111461 B FI111461 B FI 111461B FI 953851 A FI953851 A FI 953851A FI 953851 A FI953851 A FI 953851A FI 111461 B FI111461 B FI 111461B
- Authority
- FI
- Finland
- Prior art keywords
- alkyl
- trimethylsilyl
- fluoro
- trifluoro
- phenylethanone
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims description 11
- 230000008569 process Effects 0.000 title claims description 8
- 239000000544 cholinesterase inhibitor Substances 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- 239000000203 mixture Substances 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
- 150000004820 halides Chemical group 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- 229910003002 lithium salt Inorganic materials 0.000 claims description 4
- 159000000002 lithium salts Chemical class 0.000 claims description 4
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 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 description 2
- 150000001263 acyl chlorides Chemical class 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 abstract description 9
- 230000003412 degenerative effect Effects 0.000 abstract description 4
- 150000001491 aromatic compounds Chemical class 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- -1 alkyl radicals Chemical class 0.000 description 77
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- 239000012267 brine Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
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- 239000000460 chlorine Substances 0.000 description 8
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
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- 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
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
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- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 6
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- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 5
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- 235000010288 sodium nitrite Nutrition 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- OABDZAYYWSTNEV-UHFFFAOYSA-N 2-fluoro-5-trimethylsilylaniline Chemical compound C[Si](C)(C)C1=CC=C(F)C(N)=C1 OABDZAYYWSTNEV-UHFFFAOYSA-N 0.000 description 3
- 102000012440 Acetylcholinesterase Human genes 0.000 description 3
- 108010022752 Acetylcholinesterase Proteins 0.000 description 3
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229910004013 NO 2 Inorganic materials 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229940022698 acetylcholinesterase Drugs 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
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- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001935 tetracenyl group Chemical group C1(=CC=CC2=CC3=CC4=CC=CC=C4C=C3C=C12)* 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- KXFSUVJPEQYUGN-UHFFFAOYSA-N trimethyl(phenyl)silane Chemical compound C[Si](C)(C)C1=CC=CC=C1 KXFSUVJPEQYUGN-UHFFFAOYSA-N 0.000 description 1
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- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
-
- 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
- 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)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Psychiatry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP93400385A EP0611769A1 (fr) | 1993-02-16 | 1993-02-16 | Inhibiteurs d'acétylcholinerase silylés |
| EP93400385 | 1993-02-16 | ||
| US9400720 | 1994-01-25 | ||
| PCT/US1994/000720 WO1994019356A1 (fr) | 1993-02-16 | 1994-01-25 | Inhibiteurs d'acetylcholinesterase silyles |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI953851A0 FI953851A0 (fi) | 1995-08-15 |
| FI953851A FI953851A (fi) | 1995-08-15 |
| FI111461B true FI111461B (fi) | 2003-07-31 |
Family
ID=8214682
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI953851A FI111461B (fi) | 1993-02-16 | 1995-08-15 | Menetelmä terapeuttisesti käyttökelpoisten silyloitujen asetyylikoliiniesteraasi-inhibiittorien valmistamiseksi |
Country Status (19)
| Country | Link |
|---|---|
| EP (2) | EP0611769A1 (fr) |
| JP (1) | JP3516955B2 (fr) |
| KR (1) | KR100336547B1 (fr) |
| CN (1) | CN1043575C (fr) |
| AT (1) | ATE152725T1 (fr) |
| AU (1) | AU672885B2 (fr) |
| CA (1) | CA2154870C (fr) |
| DE (1) | DE69403068T2 (fr) |
| DK (1) | DK0684951T3 (fr) |
| ES (1) | ES2104358T3 (fr) |
| FI (1) | FI111461B (fr) |
| GR (1) | GR3024151T3 (fr) |
| HU (1) | HUT72736A (fr) |
| IL (1) | IL108623A0 (fr) |
| MX (1) | MX9401175A (fr) |
| NO (1) | NO305517B1 (fr) |
| NZ (1) | NZ262247A (fr) |
| WO (1) | WO1994019356A1 (fr) |
| ZA (1) | ZA94925B (fr) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0627400A1 (fr) * | 1993-06-04 | 1994-12-07 | Merrell Dow Pharmaceuticals Inc. | Inhibiteurs aromatiques d'acétylcholinesterase |
| CN100431539C (zh) * | 2004-01-12 | 2008-11-12 | 和泓生物技术（上海）有限公司 | 乙酰胆碱酯酶抑制剂在制备治疗帕金森病药物中的应用 |
| WO2008055945A1 (fr) | 2006-11-09 | 2008-05-15 | Probiodrug Ag | Dérivés 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one utiles en tant qu' inhibiteurs de la glutaminyl-cyclase dans le traitement des ulcères, du cancer et d'autres maladies |
| SI2091948T1 (sl) | 2006-11-30 | 2012-07-31 | Probiodrug Ag | Novi inhibitorji glutaminil ciklaze |
| ZA200905537B (en) | 2007-03-01 | 2010-10-27 | Probiodrug Ag | New use of glutaminyl cyclase inhibitors |
| EP2142514B1 (fr) | 2007-04-18 | 2014-12-24 | Probiodrug AG | Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase |
| ES2548913T3 (es) | 2009-09-11 | 2015-10-21 | Probiodrug Ag | Derivados heterocíclicos como inhibidores de glutaminil ciclasa |
| US20110212928A1 (en) | 2010-02-09 | 2011-09-01 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| JP6026284B2 (ja) | 2010-03-03 | 2016-11-16 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤 |
| JP5688745B2 (ja) | 2010-03-10 | 2015-03-25 | プロビオドルグ エージー | グルタミニルシクラーゼ（ｑｃ、ｅｃ２．３．２．５）の複素環阻害剤 |
| WO2011131748A2 (fr) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Nouveaux inhibiteurs |
| WO2012123563A1 (fr) | 2011-03-16 | 2012-09-20 | Probiodrug Ag | Dérivés de benzimidazole en tant qu'inhibiteurs de la glutaminyl cyclase |
| EP2919788A4 (fr) | 2012-11-14 | 2016-05-25 | Univ Johns Hopkins | Méthodes et compositions pour le traitement de la schizophrénie |
| US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| ES2881081T3 (es) | 2013-03-15 | 2021-11-26 | Agenebio Inc | Procedimientos y composiciones para mejorar la función cognitiva |
| 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 |
| EP3461819B1 (fr) | 2017-09-29 | 2020-05-27 | Probiodrug AG | Inhibiteurs de la glutaminyl-cyclase |
| CN112047973B (zh) * | 2019-06-06 | 2022-11-18 | 上海科技大学 | 一种大麻素类化合物，其制备方法、组合物和用途 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0403713A1 (fr) * | 1989-06-22 | 1990-12-27 | Merrell Dow Pharmaceuticals Inc. | Inhibiteurs d'acétylcholinestérase |
-
1993
- 1993-02-16 EP EP93400385A patent/EP0611769A1/fr not_active Withdrawn
-
1994
- 1994-01-25 NZ NZ262247A patent/NZ262247A/en unknown
- 1994-01-25 CN CN94191196A patent/CN1043575C/zh not_active Expired - Fee Related
- 1994-01-25 DE DE69403068T patent/DE69403068T2/de not_active Expired - Lifetime
- 1994-01-25 AT AT94908615T patent/ATE152725T1/de active
- 1994-01-25 KR KR1019950703485A patent/KR100336547B1/ko not_active IP Right Cessation
- 1994-01-25 ES ES94908615T patent/ES2104358T3/es not_active Expired - Lifetime
- 1994-01-25 JP JP51897494A patent/JP3516955B2/ja not_active Expired - Fee Related
- 1994-01-25 EP EP94908615A patent/EP0684951B1/fr not_active Expired - Lifetime
- 1994-01-25 DK DK94908615.1T patent/DK0684951T3/da active
- 1994-01-25 WO PCT/US1994/000720 patent/WO1994019356A1/fr active IP Right Grant
- 1994-01-25 HU HU9502406A patent/HUT72736A/hu unknown
- 1994-01-25 AU AU61641/94A patent/AU672885B2/en not_active Ceased
- 1994-01-25 CA CA002154870A patent/CA2154870C/fr not_active Expired - Fee Related
- 1994-02-10 ZA ZA94925A patent/ZA94925B/xx unknown
- 1994-02-11 IL IL10862394A patent/IL108623A0/xx unknown
- 1994-02-15 MX MX9401175A patent/MX9401175A/es not_active Application Discontinuation
-
1995
- 1995-08-15 FI FI953851A patent/FI111461B/fi not_active IP Right Cessation
- 1995-08-15 NO NO953201A patent/NO305517B1/no unknown
-
1997
- 1997-07-16 GR GR970401801T patent/GR3024151T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO953201L (no) | 1995-08-15 |
| EP0611769A1 (fr) | 1994-08-24 |
| NO953201D0 (no) | 1995-08-15 |
| KR100336547B1 (ko) | 2002-11-02 |
| FI953851A0 (fi) | 1995-08-15 |
| FI953851A (fi) | 1995-08-15 |
| AU6164194A (en) | 1994-09-14 |
| JP3516955B2 (ja) | 2004-04-05 |
| DE69403068D1 (en) | 1997-06-12 |
| HUT72736A (en) | 1996-05-28 |
| DK0684951T3 (da) | 1997-05-26 |
| CN1043575C (zh) | 1999-06-09 |
| ES2104358T3 (es) | 1997-10-01 |
| DE69403068T2 (de) | 1997-12-11 |
| AU672885B2 (en) | 1996-10-17 |
| GR3024151T3 (en) | 1997-10-31 |
| ZA94925B (en) | 1994-08-25 |
| CA2154870C (fr) | 1998-10-27 |
| CN1117733A (zh) | 1996-02-28 |
| KR960701068A (ko) | 1996-02-24 |
| WO1994019356A1 (fr) | 1994-09-01 |
| EP0684951B1 (fr) | 1997-05-07 |
| EP0684951A1 (fr) | 1995-12-06 |
| NZ262247A (en) | 1996-01-26 |
| MX9401175A (es) | 1994-08-31 |
| JPH08507059A (ja) | 1996-07-30 |
| CA2154870A1 (fr) | 1994-09-01 |
| NO305517B1 (no) | 1999-06-14 |
| IL108623A0 (en) | 1994-05-30 |
| ATE152725T1 (de) | 1997-05-15 |
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Owner name: AVENTIS INC. Free format text: AVENTIS INC. |
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| PC | Transfer of assignment of patent |
Owner name: AVENTISUB II INC. Free format text: AVENTISUB II INC. |
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| MM | Patent lapsed |