LU84011A1 - 2-phenoxyalkyl-1,2,4-triazol-3-ones antidepressives - Google Patents
2-phenoxyalkyl-1,2,4-triazol-3-ones antidepressives Download PDFInfo
- Publication number
- LU84011A1 LU84011A1 LU84011A LU84011A LU84011A1 LU 84011 A1 LU84011 A1 LU 84011A1 LU 84011 A LU84011 A LU 84011A LU 84011 A LU84011 A LU 84011A LU 84011 A1 LU84011 A1 LU 84011A1
- Authority
- LU
- Luxembourg
- Prior art keywords
- formula
- triazol
- chlorophenyl
- ethyl
- radical
- Prior art date
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- 230000001430 anti-depressive effect Effects 0.000 title claims description 10
- -1 alkoxy radical Chemical class 0.000 claims description 45
- 150000001875 compounds Chemical class 0.000 claims description 45
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 38
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 150000003254 radicals Chemical class 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- 239000000935 antidepressant agent Substances 0.000 claims description 11
- 229940005513 antidepressants Drugs 0.000 claims description 11
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- 238000002360 preparation method Methods 0.000 claims description 10
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- 230000008569 process Effects 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
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- PVVXNFVGILZMLZ-UHFFFAOYSA-N 4-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-5-ethyl-2-(2-phenoxyethyl)-1,2,4-triazol-3-one Chemical compound O=C1N(CCCN2CCN(CC2)C=2C=C(Cl)C=CC=2)C(CC)=NN1CCOC1=CC=CC=C1 PVVXNFVGILZMLZ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
- C07D295/067—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/244,464 US4338317A (en) | 1981-03-16 | 1981-03-16 | Phenoxyethyl-1,2,4,-triazol-3-one antidepressants |
| US24446481 | 1981-03-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| LU84011A1 true LU84011A1 (fr) | 1983-02-22 |
Family
ID=22922879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LU84011A LU84011A1 (fr) | 1981-03-16 | 1982-03-15 | 2-phenoxyalkyl-1,2,4-triazol-3-ones antidepressives |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US4338317A (en]) |
| JP (1) | JPS57159774A (en]) |
| KR (1) | KR880001374B1 (en]) |
| AT (1) | AT384022B (en]) |
| BE (1) | BE892503A (en]) |
| CA (1) | CA1198436A (en]) |
| CH (1) | CH649539A5 (en]) |
| CY (1) | CY1373A (en]) |
| DE (1) | DE3209557A1 (en]) |
| DK (1) | DK158728C (en]) |
| ES (1) | ES8305756A1 (en]) |
| FI (1) | FI73670C (en]) |
| FR (1) | FR2501690B1 (en]) |
| GB (1) | GB2096137B (en]) |
| GR (1) | GR76076B (en]) |
| HK (1) | HK4788A (en]) |
| IE (1) | IE52788B1 (en]) |
| IT (1) | IT1148137B (en]) |
| KE (1) | KE3711A (en]) |
| LU (1) | LU84011A1 (en]) |
| MX (1) | MX9203176A (en]) |
| NL (2) | NL190757C (en]) |
| SE (1) | SE447256B (en]) |
| SG (1) | SG30287G (en]) |
| YU (1) | YU43256B (en]) |
| ZA (1) | ZA821359B (en]) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4487773A (en) * | 1981-03-16 | 1984-12-11 | Mead Johnson & Company | 1,2,4-Triazol-3-one antidepressants |
| US4386091A (en) * | 1982-02-24 | 1983-05-31 | Mead Johnson & Company | 2-Phenoxyalkyl-1,2,4-triazol-3-one antidepressants |
| US4575555A (en) * | 1983-06-29 | 1986-03-11 | Mead Johnson & Company | 4-(3-Chlorophenyl)-1,2,3,6-tetrahydropyridine derivative |
| AT388555B (de) * | 1983-06-29 | 1989-07-25 | Bristol Myers Co | Verfahren zur herstellung von neuen 1,2,4-triazol-3-on-derivaten |
| US4613600A (en) * | 1983-09-30 | 1986-09-23 | Mead Johnson & Company | Antidepressant 1,2,4-triazolone compounds |
| YU44721B (en) * | 1983-11-30 | 1990-12-31 | Bristol Myers Co | Process for obtaining 4-(2-phenoxyethyl)-1,2,4-triazolone |
| CA1248531A (en) * | 1984-04-17 | 1989-01-10 | Jeffrey C. Watkins | 4-substituted piperazine-2-carboxylic acids |
| US4784998A (en) * | 1987-04-06 | 1988-11-15 | Bristol-Myers Company | 1,3,4-oxadiazole pyschotropic compounds |
| US5116852A (en) * | 1990-12-03 | 1992-05-26 | Bristol-Myers Squibb Co. | Treatment of sleep disorders |
| US5266571A (en) * | 1992-01-09 | 1993-11-30 | Amer Moh Samir | Treatment of hemorrhoids with 5-HT2 antagonists |
| US5256664A (en) * | 1992-04-28 | 1993-10-26 | Bristol-Myers Squibb Company | Antidepressant 3-halophenylpiperazinylpropyl derivatives of substituted triazolones and triazoldiones |
| IT1256387B (it) * | 1992-11-13 | 1995-12-04 | Acraf | Procedimento per preparare triazoloni |
| DE4425144A1 (de) * | 1994-07-15 | 1996-01-18 | Basf Ag | Triazolverbindungen und deren Verwendung |
| CA2160423A1 (en) * | 1994-11-02 | 1996-05-03 | Hemant N. Joshi | Salts of nefazodone having improved dissolution rates |
| AU7025396A (en) | 1995-10-17 | 1997-05-01 | Bristol-Myers Squibb Company | Nefazodone: treatment of panic attack |
| CA2182241C (en) * | 1996-07-29 | 2002-09-17 | Bo Lei | Methods for the manufacture of nefazodone |
| WO1998004261A1 (en) * | 1996-07-31 | 1998-02-05 | Bristol-Myers Squibb Company | Nefazodone: use in migraine prophylaxis |
| US5852020A (en) * | 1996-11-22 | 1998-12-22 | Bristol-Myers Squibb Company | Nefazodone: use in treating post traumatic stress disorder |
| US5735873A (en) * | 1996-12-19 | 1998-04-07 | Maclean; David S. | Surgical tool handle |
| US5917050A (en) * | 1998-02-11 | 1999-06-29 | Bayer Corporation | Process for preparing alkoxytriazolinones |
| ES2152860B1 (es) * | 1998-10-23 | 2001-08-16 | Finaf 92 Sa | Forma cristalina de la nefazodona y procedimiento para su preparacion. |
| US6706282B1 (en) | 1998-11-02 | 2004-03-16 | Evangeline Cruz | Controlled delivery of phenoxyethyl-substituted 1,2,4-triazolones |
| US6469008B2 (en) | 1999-04-09 | 2002-10-22 | Sepracor Inc. | (R)-hydroxynefazodone antipsychotic therapy |
| US6465469B1 (en) | 1999-04-09 | 2002-10-15 | Sepracor Inc. | S-hydroxynefazodone |
| US6586437B2 (en) | 1999-04-09 | 2003-07-01 | Sepracor Inc. | (S)-hydroxynefazodone antipsychotic therapy |
| WO2000061128A2 (en) * | 1999-04-09 | 2000-10-19 | Sepracor Inc. | R-hydroxynefazodone |
| CA97021S (en) | 2001-03-02 | 2003-06-25 | Nokia Mobile Phones Ltd | Handset |
| AU144901S (en) | 2001-03-02 | 2001-08-15 | Nokia Mobile Phones Ltd | A handset |
| AU144906S (en) | 2001-03-02 | 2001-08-15 | Nokia Mobile Phones Ltd | A handset |
| AU144902S (en) | 2001-03-02 | 2001-08-15 | Nokia Mobile Phones Ltd | A handset |
| CA2356450C (en) | 2001-09-10 | 2003-11-25 | Brantford Chemicals Inc. | An improved process for the preparation of nefazodone hydrochloride |
| EP1513533B1 (de) * | 2002-05-24 | 2010-03-17 | Carl-Fr. Coester | Pharmazeutische wirkstoffkombination sowie deren verwendung |
| GB0306604D0 (en) * | 2003-03-21 | 2003-04-30 | Curidium Ltd | Second medical use |
| KR20060003055A (ko) * | 2003-04-30 | 2006-01-09 | 에프엠씨 코포레이션 | 살충성 (다이할로프로펜일)페닐알킬 치환된다이하이드로벤조퓨란 및 다이하이드로벤조피란 유도체 |
| EP1689721B1 (en) * | 2003-11-26 | 2010-07-14 | Pfizer Products Inc. | Aminopyrazole derivatives as gsk-3 inhibitors |
| CA2567249A1 (en) * | 2004-04-19 | 2006-10-05 | Jds Pharmaceuticals, Llc | Lithium combinations, and uses related thereto |
| AR049382A1 (es) * | 2004-05-18 | 2006-07-26 | Fmc Corp | Derivados de la urea ciclica substituida |
| SG163588A1 (en) | 2005-07-08 | 2010-08-30 | Braincells Inc | Methods for identifying agents and conditions that modulate neurogenesis |
| US7985756B2 (en) | 2005-10-21 | 2011-07-26 | Braincells Inc. | Modulation of neurogenesis by PDE inhibition |
| EP1942879A1 (en) | 2005-10-31 | 2008-07-16 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| CA2651813A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| MX2008014320A (es) | 2006-05-09 | 2009-03-25 | Braincells Inc | Neurogenesis mediada por el receptor de 5-hidroxitriptamina. |
| US7858611B2 (en) * | 2006-05-09 | 2010-12-28 | Braincells Inc. | Neurogenesis by modulating angiotensin |
| CA2662491A1 (en) | 2006-09-08 | 2008-03-13 | Braincells, Inc. | Combinations containing a 4-acylaminopyridine derivative |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| US20080167363A1 (en) * | 2006-12-28 | 2008-07-10 | Braincells, Inc | Modulation of Neurogenesis By Melatoninergic Agents |
| WO2008086483A2 (en) * | 2007-01-11 | 2008-07-17 | Braincells, Inc. | Modulation of neurogenesis with use of modafinil |
| JP5358571B2 (ja) * | 2007-08-07 | 2013-12-04 | プロサリク リミテッド | セロトニン作動性調節因子としての１，２，４−トリアゾール誘導体 |
| WO2009111031A2 (en) | 2008-03-04 | 2009-09-11 | Intra-Cellular Therapies, Inc. | Methods of treating vasomotor symptoms |
| WO2009128058A1 (en) | 2008-04-18 | 2009-10-22 | UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN et al | Psycho-pharmaceuticals |
| WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| TWI368512B (en) * | 2009-04-30 | 2012-07-21 | Univ Kaohsiung Medical | Pharmaceutical compositions comprising chlorophenyl piperazine derived compounds and use of the compounds in producing medicaments |
| WO2012072665A1 (en) | 2010-11-30 | 2012-06-07 | Pharmaneuroboost N.V. | Compositions comprising pipamperone and serotonin antagonist reuptake inhibitors |
| CN104402842A (zh) * | 2014-11-19 | 2015-03-11 | 苏州乔纳森新材料科技有限公司 | 一种哌嗪类药物中间体的合成方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1066857B (it) * | 1965-12-15 | 1985-03-12 | Acraf | Derivati della s ipiazolo 4.3 a piridina e processi per la loro preparazione |
| IT1052119B (it) * | 1972-10-16 | 1981-06-20 | Sigma Tau Ind Farmaceuti | Derivati del triazolinone e procedimento per la loro preparazione |
-
1981
- 1981-03-16 US US06/244,464 patent/US4338317A/en not_active Expired - Lifetime
-
1982
- 1982-03-02 ZA ZA821359A patent/ZA821359B/xx unknown
- 1982-03-08 CA CA000397793A patent/CA1198436A/en not_active Expired
- 1982-03-09 GR GR67529A patent/GR76076B/el unknown
- 1982-03-11 YU YU525/82A patent/YU43256B/xx unknown
- 1982-03-11 NL NL8201021A patent/NL190757C/xx not_active IP Right Cessation
- 1982-03-12 DK DK112582A patent/DK158728C/da not_active IP Right Cessation
- 1982-03-12 FI FI820856A patent/FI73670C/fi not_active IP Right Cessation
- 1982-03-12 IT IT47978/82A patent/IT1148137B/it active Protection Beyond IP Right Term
- 1982-03-15 BE BE0/207574A patent/BE892503A/fr not_active IP Right Cessation
- 1982-03-15 SE SE8201631A patent/SE447256B/sv not_active IP Right Cessation
- 1982-03-15 LU LU84011A patent/LU84011A1/fr unknown
- 1982-03-15 GB GB8207539A patent/GB2096137B/en not_active Expired
- 1982-03-15 CY CY137382A patent/CY1373A/en unknown
- 1982-03-15 CH CH1615/82A patent/CH649539A5/de not_active IP Right Cessation
- 1982-03-15 IE IE589/82A patent/IE52788B1/en active Protection Beyond IP Right Term
- 1982-03-15 ES ES510449A patent/ES8305756A1/es not_active Expired
- 1982-03-15 FR FR8204325A patent/FR2501690B1/fr not_active Expired
- 1982-03-16 DE DE19823209557 patent/DE3209557A1/de active Granted
- 1982-03-16 KR KR8201129A patent/KR880001374B1/ko not_active Expired
- 1982-03-16 AT AT0104582A patent/AT384022B/de not_active IP Right Cessation
- 1982-03-16 JP JP57040315A patent/JPS57159774A/ja active Granted
-
1987
- 1987-03-27 SG SG302/87A patent/SG30287G/en unknown
- 1987-03-31 KE KE3711A patent/KE3711A/xx unknown
-
1988
- 1988-01-21 HK HK47/88A patent/HK4788A/xx not_active IP Right Cessation
-
1992
- 1992-06-23 MX MX9203176A patent/MX9203176A/es unknown
-
1997
- 1997-03-17 NL NL970014C patent/NL970014I2/nl unknown
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