EA005768B1 - Ингибирование поглощения моноамина - Google Patents
Ингибирование поглощения моноамина Download PDFInfo
- Publication number
- EA005768B1 EA005768B1 EA200300978A EA200300978A EA005768B1 EA 005768 B1 EA005768 B1 EA 005768B1 EA 200300978 A EA200300978 A EA 200300978A EA 200300978 A EA200300978 A EA 200300978A EA 005768 B1 EA005768 B1 EA 005768B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- methyl
- phenyl
- oxy
- aminopropane
- compound
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 56
- -1 methyl-3 ((2-methyl-4-hydroxyphenyl) oxy) -3-phenyl-1-aminopropane hydrochloride Chemical compound 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 12
- 239000003085 diluting agent Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 239000000314 lubricant Substances 0.000 claims description 4
- 229920002545 silicone oil Polymers 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000007903 gelatin capsule Substances 0.000 claims description 2
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 14
- 241000124008 Mammalia Species 0.000 abstract description 8
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- 230000002503 metabolic effect Effects 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
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- 239000002904 solvent Substances 0.000 description 12
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- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
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- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
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- VHGCDTVCOLNTBX-QGZVFWFLSA-N atomoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=CC=C1C VHGCDTVCOLNTBX-QGZVFWFLSA-N 0.000 description 8
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- DHWJJZIIARZDIS-UHFFFAOYSA-N 4-(3-amino-1-phenylbutoxy)-3-methylphenol Chemical compound C=1C=CC=CC=1C(CC(N)C)OC1=CC=C(O)C=C1C DHWJJZIIARZDIS-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
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- 238000010561 standard procedure Methods 0.000 description 6
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- CNHDIAIOKMXOLK-UHFFFAOYSA-N toluquinol Chemical compound CC1=CC(O)=CC=C1O CNHDIAIOKMXOLK-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
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- 210000002381 plasma Anatomy 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- JZFUHAGLMZWKTF-UHFFFAOYSA-N 3-chloro-1-phenylpropan-1-ol Chemical compound ClCCC(O)C1=CC=CC=C1 JZFUHAGLMZWKTF-UHFFFAOYSA-N 0.000 description 3
- BAZDSWGZNBANTB-UHFFFAOYSA-N 4-(2-methylphenoxy)-4-phenylbutan-2-amine;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(N)C)OC1=CC=CC=C1C BAZDSWGZNBANTB-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 235000011293 Brassica napus Nutrition 0.000 description 3
- 240000008100 Brassica rapa Species 0.000 description 3
- 235000000540 Brassica rapa subsp rapa Nutrition 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
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- 241000700159 Rattus Species 0.000 description 3
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- 238000005576 amination reaction Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000750 constant-initial-state spectroscopy Methods 0.000 description 3
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- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- XJSIOIUWJIMDDN-UHFFFAOYSA-N (4-hydroxy-3-methylphenyl) acetate Chemical compound CC(=O)OC1=CC=C(O)C(C)=C1 XJSIOIUWJIMDDN-UHFFFAOYSA-N 0.000 description 2
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 2
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- XXSDCGNHLFVSET-UHFFFAOYSA-N 3-(methylamino)-1-phenylpropan-1-ol Chemical compound CNCCC(O)C1=CC=CC=C1 XXSDCGNHLFVSET-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/48—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Pulmonology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Anesthesiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Gynecology & Obstetrics (AREA)
- Child & Adolescent Psychology (AREA)
- Immunology (AREA)
- Otolaryngology (AREA)
- Urology & Nephrology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27373001P | 2001-03-06 | 2001-03-06 | |
| PCT/US2002/003385 WO2002070457A1 (en) | 2001-03-06 | 2002-02-20 | Inhibitor of monoamine uptake |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200300978A1 EA200300978A1 (ru) | 2004-02-26 |
| EA005768B1 true EA005768B1 (ru) | 2005-06-30 |
Family
ID=23045157
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200300978A EA005768B1 (ru) | 2001-03-06 | 2002-02-20 | Ингибирование поглощения моноамина |
Country Status (35)
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1229331C (zh) * | 2001-03-06 | 2005-11-30 | 伊莱利利公司 | 一元胺吸收的抑制剂 |
| WO2005020976A2 (en) * | 2003-08-27 | 2005-03-10 | Eli Lilly And Company | Treatment of pervasive developmental disorders with norepinephrine reuptake inhibitors |
| KR20060121178A (ko) * | 2003-12-12 | 2006-11-28 | 일라이 릴리 앤드 캄파니 | 일과성 전신 열감, 충동 조절 장애 및 일반적인 의학상태로 인한 인격 변화 치료용 선택적 노르에피네프린재흡수 억제제 |
| WO2011027359A2 (en) * | 2009-07-30 | 2011-03-10 | Matrix Laboratories Ltd | Novel process for the preparation of 4-hydroxy atomoxetine |
| WO2012020418A1 (en) | 2010-08-12 | 2012-02-16 | Matrix Laboratories Ltd | Novel polymorphs of 4-hydroxy atomoxetine hydrochloride |
| DE102013022397A1 (de) | 2013-12-19 | 2016-07-07 | Metrax Gmbh | Vorrichtung zur Unterstützung eines Ersthelfers bei der Herzdruckmassage |
| GR1008819B (el) | 2015-05-22 | 2016-08-01 | Φαρματεν Ανωνυμος Βιομηχανικη Και Εμπορικη Εταιρεια Φαρμακευτικων Ιατρικων Και Καλλυντικων Προϊοντων | Φαρμακευτικο σκευασμα που περιλαμβανει ατομοξετινη και μεθοδος παρασκευης αυτου |
| CN107935848B (zh) * | 2017-11-21 | 2020-12-22 | 中国农业科学院兰州畜牧与兽药研究所 | 一种六茜素衍生物及其制备方法和应用 |
| JP2022506113A (ja) * | 2018-10-31 | 2022-01-17 | アプニメッド，インコーポレイテッド（デラウェア） | 睡眠時無呼吸を治療するための方法及び組成物 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4314081A (en) * | 1974-01-10 | 1982-02-02 | Eli Lilly And Company | Arloxyphenylpropylamines |
| US4018895A (en) | 1974-01-10 | 1977-04-19 | Eli Lilly And Company | Aryloxyphenylpropylamines in treating depression |
| US4194009A (en) | 1974-01-10 | 1980-03-18 | Eli Lilly And Company | Aryloxyphenylpropylamines for obtaining a psychotropic effect |
| FR2432500A1 (fr) * | 1978-02-24 | 1980-02-29 | Roussel Uclaf | Nouveaux derives de la benzene propanamine et leurs sels, procede de preparation et application a titre de medicaments |
| US5112619A (en) * | 1985-11-12 | 1992-05-12 | Eli Lilly And Company | Orally administerable sustained release pharmaceutical formulation |
| US4956388A (en) | 1986-12-22 | 1990-09-11 | Eli Lilly And Company | 3-aryloxy-3-substituted propanamines |
| ZA885824B (en) * | 1987-08-14 | 1989-04-26 | Merrell Dow Pharma | Novel antidepressants |
| ZA921292B (en) * | 1991-02-25 | 1993-08-23 | Lilly Co Eli | Treatment of lower urinary tract disorders. |
| TW514634B (en) | 1997-10-14 | 2002-12-21 | Lilly Co Eli | Process to make chiral compounds |
| WO2000058262A1 (en) | 1999-03-29 | 2000-10-05 | Eli Lilly And Company | Stereospecific method for preparing tomoxetine and intermediates thereof |
| ATE309196T1 (de) | 1999-04-09 | 2005-11-15 | Lilly Co Eli | Verfahren zur herstellung von 3-aryloxy-3- arylpropylamine und deren zwischenprodukte |
| EP1395253A2 (en) * | 2000-11-15 | 2004-03-10 | Eli Lilly And Company | Treatment of anxiety disorders |
| CN1229331C (zh) * | 2001-03-06 | 2005-11-30 | 伊莱利利公司 | 一元胺吸收的抑制剂 |
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2002
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- 2002-02-20 PL PL02363840A patent/PL363840A1/xx not_active Application Discontinuation
- 2002-02-20 FI FI20031191A patent/FI20031191A7/fi not_active IP Right Cessation
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- 2002-02-20 AT AT02713538T patent/ATE396170T1/de not_active IP Right Cessation
- 2002-02-20 NZ NZ527431A patent/NZ527431A/en unknown
- 2002-02-20 US US10/468,553 patent/US20040082666A1/en not_active Abandoned
- 2002-02-20 CA CA002440161A patent/CA2440161A1/en not_active Abandoned
- 2002-02-20 AP APAP/P/2003/002855A patent/AP2003002855A0/en unknown
- 2002-02-20 AT AT0904202A patent/AT414238B/de not_active IP Right Cessation
- 2002-02-20 LU LU91038A patent/LU91038B1/fr active
- 2002-02-20 EE EEP200300419A patent/EE200300419A/xx unknown
- 2002-02-20 HR HR20030710A patent/HRP20030710A2/hr not_active Application Discontinuation
- 2002-02-20 IL IL15777902A patent/IL157779A0/xx unknown
- 2002-02-20 SK SK1063-2003A patent/SK10632003A3/sk unknown
- 2002-02-20 CH CH01522/03A patent/CH695982A5/de not_active IP Right Cessation
- 2002-02-20 CZ CZ20032380A patent/CZ20032380A3/cs unknown
- 2002-02-20 KR KR10-2003-7011635A patent/KR20030092012A/ko not_active Ceased
- 2002-02-20 DE DE60226715T patent/DE60226715D1/de not_active Revoked
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- 2002-02-20 JP JP2002569778A patent/JP2004525912A/ja not_active Ceased
- 2002-02-20 BR BR0207716-7A patent/BR0207716A/pt not_active IP Right Cessation
- 2002-02-20 ES ES02713538T patent/ES2305221T3/es not_active Expired - Lifetime
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- 2002-02-20 HU HU0303341A patent/HUP0303341A3/hu unknown
- 2002-02-20 EP EP02713538A patent/EP1379492B1/en not_active Revoked
- 2002-02-20 GB GB0323169A patent/GB2389851B/en not_active Expired - Fee Related
- 2002-02-20 OA OA1200300215A patent/OA12494A/en unknown
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2003
- 2003-08-11 LT LT2003075A patent/LT5143B/lt unknown
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- 2003-09-03 SE SE0302361A patent/SE526598C2/sv not_active IP Right Cessation
- 2003-09-03 ZA ZA200306882A patent/ZA200306882B/en unknown
- 2003-09-04 DK DK200301267A patent/DK200301267A/da not_active Application Discontinuation
- 2003-09-04 NO NO20033921A patent/NO20033921L/no not_active Application Discontinuation
- 2003-09-10 LV LVP-03-100A patent/LV13119B/en unknown
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2005
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ KG MD TJ TM |