BRPI0415070A - derivados de dibenzo-azepina e benzo-diazepina substituìdos úteis como inibidores de gama-secretase - Google Patents
derivados de dibenzo-azepina e benzo-diazepina substituìdos úteis como inibidores de gama-secretaseInfo
- Publication number
- BRPI0415070A BRPI0415070A BRPI0415070-8A BRPI0415070A BRPI0415070A BR PI0415070 A BRPI0415070 A BR PI0415070A BR PI0415070 A BRPI0415070 A BR PI0415070A BR PI0415070 A BRPI0415070 A BR PI0415070A
- Authority
- BR
- Brazil
- Prior art keywords
- lower alkyl
- hydrogen
- cycloalkyl
- derivatives useful
- substituted
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/12—1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
"DERIVADOS DE DIBENZO-AZEPINA E BENZO-DIAZEPINA SUBSTITUìDOS úTEIS COMO INIBIDORES DE GAMA-SECRETASE". A presente invenção refere-se a compostos da fórmula geral onde R¬ 1¬ é -(CHR<39>)~ q~-arila ou -(CHR<39>)~ q~-heteroarila, que são o-substituídos ou monossubstituídos, dissubstituídos ou trissubstituídos com alquila inferior, alcóxi inferior, CF~ 3~ ou halogênio, ou é alquila inferior, alquenila inferior, -(CH~ 2~)~ n~-Si(CH~ 3~)~ 3~, -(CH~ 2~)~ n~-O-alquila inferior, -(CH~ 2~)~ n~-S-alquila inferior, -(CH~ 2~)~ q~-cicloalquila, -(CH~ 2~)~ n~-¢CH(OH)!~ m~-(CF~ 2~)~ p~-CH~ q~F(~ 3-q~), ou é -(CH~ 2~)~ n~-CR~ 2~-CF~ 3~, onde os dois radicais R formam junto com o átomo de carbono um anel cicloalquila; R<39> é hidrogênio ou alquila inferior; n é 1, 2 ou 3; m é 0 ou 1; p é 0, 1, 2, 3, 4, 5 ou 6; q é 0, 1, 2 ou 3; R¬ 2¬ é hidrogênio ou alquila inferior; R¬ 3¬ é hidrogênio, alquila inferior, -CH~ 2~CF~ 2~CF~ 3~, CH~ 2~CF~ 3~, (CH~ 2~)~ 2~CF~ 3~, CF~ 3~, CHF~ 2~, CF~ 3~, CHF~ 2~, CH~ 2~F, ou é arila, opcionalmente monossubstituído, dissubstituído ou trissubstituído com halogênio, ou é -(CH~ 2~)~ n~NR¬ 5¬R¬ 6¬, onde R¬ 5¬ e R¬ 6¬ são independentemente um do outro hidrogênio ou alquila inferior; R¬ 4¬ é um dos seguintes grupos onde R¬ 7¬ é hidrogênio, alquila inferior, -(CH~ 2~)~ n~-CF~ 3~ ou -(CH~ 2~)~ n~-Cicloalquila; R¬ 8¬ é hidrogênio, alquila inferior, -C(O)-fenila, -C(O)-alquila inferior, -C(0)0-(CH~ 2~)~ n~-cicloalquila, -C(O)O-(CH~ 2~)~ n~-alquila inferior, -C(O)NH-(CH~ 2~)~ n~-alquila inferior ou -C(O)NH-(CH~ 2~)~ n~-cicloalquila; R¬ 9¬ é hidrogênio, alquila inferior, -C(O)NH-(CH~ 2~)~ n~cicloalquila ou -(CH~ 2~)~ n~CF~ 3~; e sais de adição de ácido farmaceuticamente adequados, enantiómeros oticamente puros, racematos ou misturas diastereoméricos dos mesmos para tratamento do mal de Alzheimer.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03022650 | 2003-10-06 | ||
| EP03022650.0 | 2003-10-06 | ||
| PCT/EP2004/010821 WO2005040126A1 (en) | 2003-10-06 | 2004-09-27 | Substituted dibenzo-azepine and benzo-diazepine derivatives useful as gamma-secretase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| BRPI0415070A true BRPI0415070A (pt) | 2006-12-12 |
| BRPI0415070B1 BRPI0415070B1 (pt) | 2018-05-15 |
| BRPI0415070B8 BRPI0415070B8 (pt) | 2021-05-25 |
Family
ID=34384575
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0415070A BRPI0415070B8 (pt) | 2003-10-06 | 2004-09-27 | derivados de dibenzo-azepina e benzo-diazepina substituídos úteis, seu uso e seu processo de preparação, e medicamento |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US7166587B2 (pt) |
| EP (1) | EP1673347B1 (pt) |
| JP (1) | JP4503607B2 (pt) |
| KR (2) | KR100884872B1 (pt) |
| CN (1) | CN1894217B (pt) |
| AR (1) | AR045859A1 (pt) |
| AU (1) | AU2004283803B2 (pt) |
| BR (1) | BRPI0415070B8 (pt) |
| CA (1) | CA2541470C (pt) |
| CO (1) | CO5690560A2 (pt) |
| CY (1) | CY1116865T1 (pt) |
| DK (1) | DK1673347T3 (pt) |
| ES (1) | ES2548720T3 (pt) |
| HR (1) | HRP20151197T1 (pt) |
| HU (1) | HUE025548T2 (pt) |
| IL (1) | IL174513A (pt) |
| MX (1) | MXPA06003870A (pt) |
| MY (1) | MY143797A (pt) |
| NO (1) | NO20061469L (pt) |
| NZ (1) | NZ546036A (pt) |
| PL (1) | PL1673347T3 (pt) |
| PT (1) | PT1673347E (pt) |
| RU (1) | RU2356895C2 (pt) |
| SI (1) | SI1673347T1 (pt) |
| TW (1) | TWI293627B (pt) |
| WO (1) | WO2005040126A1 (pt) |
| ZA (1) | ZA200602802B (pt) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7521481B2 (en) | 2003-02-27 | 2009-04-21 | Mclaurin Joanne | Methods of preventing, treating and diagnosing disorders of protein aggregation |
| US7211573B2 (en) | 2004-12-08 | 2007-05-01 | Hoffmann-La Roche Inc. | Malonamide derivatives |
| WO2007029587A1 (ja) * | 2005-09-05 | 2007-03-15 | Dainippon Sumitomo Pharma Co., Ltd. | βセクレターゼ阻害剤 |
| ES2398531T3 (es) * | 2006-03-27 | 2013-03-20 | F. Hoffmann-La Roche Ag | Derivados de malonamida como inhibidores de gamma secretasa |
| BRPI0717587A2 (pt) | 2006-09-20 | 2013-10-29 | Hoffmann La Roche | Derivados de 4-oxo-2,3,4,5-tetra-hidro-benzo[b][1,4]diazepina |
| EP2089383B1 (en) | 2006-11-09 | 2015-09-16 | Probiodrug AG | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
| DK2091948T3 (da) | 2006-11-30 | 2012-07-23 | Probiodrug Ag | Nye inhibitorer af glutaminylcyclase |
| MX2009007864A (es) | 2007-02-02 | 2009-07-31 | Hoffmann La Roche | Derivados de 6-oxo-6,7-dihidro-5h-dibenzo[b,d]azepin-7-ilo. |
| CA2679446C (en) | 2007-03-01 | 2016-05-17 | Probiodrug Ag | New use of glutaminyl cyclase inhibitors |
| FR2913886B1 (fr) | 2007-03-22 | 2012-03-02 | Guerbet Sa | Utilisation de nanoparticules metalliques dans le diagnostique de la maladie d'alzheimer |
| US9656991B2 (en) | 2007-04-18 | 2017-05-23 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| US7579464B2 (en) * | 2007-05-25 | 2009-08-25 | Hoffmann-La Roche Inc. | Process for preparation of enantiomerically pure compounds |
| MX2012002993A (es) | 2009-09-11 | 2012-04-19 | Probiodrug Ag | Derivados heterociclicos como inhibidores de ciclasa glutaminilo. |
| WO2011107530A2 (en) | 2010-03-03 | 2011-09-09 | Probiodrug Ag | Novel inhibitors |
| 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 |
| EP2560953B1 (en) | 2010-04-21 | 2016-01-06 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
| WO2011140213A1 (en) * | 2010-05-05 | 2011-11-10 | Amicus Therapeutics, Inc. | Method of treating alzheimer's disease using pharmacological chaperones to increase presenilin function and gamma-secretase activity |
| ES2570167T3 (es) | 2011-03-16 | 2016-05-17 | Probiodrug Ag | Derivados de benzimidazol como inhibidores de glutaminil ciclasa |
| JO3148B1 (ar) | 2011-07-27 | 2017-09-20 | Lilly Co Eli | مركب مثبط لإشارات مسار notch |
| KR102130458B1 (ko) * | 2015-10-30 | 2020-07-08 | 파이프라인 테라퓨틱스, 아이엔씨. | 디벤조 아제핀 화합물 및 귀 질환과 귀 장애 치료에서의 그의 용도 |
| AU2017376109A1 (en) | 2016-12-16 | 2019-07-11 | Pipeline Therapeutics, Inc. | Methods of treating cochlear synaptopathy |
| ES2812698T3 (es) | 2017-09-29 | 2021-03-18 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
| US20210220372A1 (en) * | 2018-05-15 | 2021-07-22 | Bristol-Myers Squibb Company | Compositions comprising bisfluoroalkyl-1,4-benzodiazepinone compounds and methods of use thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1313426A4 (en) * | 1998-12-24 | 2003-05-28 | Bristol Myers Squibb Pharma Co | SUCCINOYLAMINOBENZODIAZEPINE AS INHIBITORS OF A-BETA PROTEIN PRODUCTION |
| CA2404273A1 (en) * | 2000-04-11 | 2001-10-18 | Bristol-Myers Squibb Pharma Company | Substituted lactams as inhibitors of a.beta. protein production |
| WO2001092235A1 (en) * | 2000-06-01 | 2001-12-06 | Bristol-Myers Squibb Pharma Company | LACTAMS SUBSTITUTED BY CYCLIC SUCCINATES AS INHIBITORS OF Aβ PROTEIN PRODUCTION |
| WO2004069826A1 (en) * | 2003-02-04 | 2004-08-19 | F. Hoffmann-La Roche Ag | Malonamide derivatives as gamma-secretase inhibitors |
| DK1711470T3 (da) * | 2003-09-09 | 2009-06-08 | Hoffmann La Roche | Malonamidderivater der blokerer aktiviteten af gamma-sekretase |
-
2004
- 2004-09-27 AU AU2004283803A patent/AU2004283803B2/en active Active
- 2004-09-27 SI SI200432267T patent/SI1673347T1/sl unknown
- 2004-09-27 CA CA2541470A patent/CA2541470C/en active Active
- 2004-09-27 KR KR1020087003016A patent/KR100884872B1/ko active IP Right Grant
- 2004-09-27 KR KR1020067006540A patent/KR100867035B1/ko active IP Right Grant
- 2004-09-27 JP JP2006530028A patent/JP4503607B2/ja active Active
- 2004-09-27 NZ NZ546036A patent/NZ546036A/en unknown
- 2004-09-27 CN CN2004800333748A patent/CN1894217B/zh active Active
- 2004-09-27 ES ES04787028.2T patent/ES2548720T3/es active Active
- 2004-09-27 PL PL04787028T patent/PL1673347T3/pl unknown
- 2004-09-27 MX MXPA06003870A patent/MXPA06003870A/es active IP Right Grant
- 2004-09-27 PT PT47870282T patent/PT1673347E/pt unknown
- 2004-09-27 US US10/951,229 patent/US7166587B2/en active Active
- 2004-09-27 BR BRPI0415070A patent/BRPI0415070B8/pt active IP Right Grant
- 2004-09-27 EP EP04787028.2A patent/EP1673347B1/en active Active
- 2004-09-27 DK DK04787028.2T patent/DK1673347T3/en active
- 2004-09-27 HU HUE04787028A patent/HUE025548T2/en unknown
- 2004-09-27 RU RU2006115165/04A patent/RU2356895C2/ru not_active IP Right Cessation
- 2004-09-27 WO PCT/EP2004/010821 patent/WO2005040126A1/en active Application Filing
- 2004-10-04 AR ARP040103592A patent/AR045859A1/es unknown
- 2004-10-04 TW TW093130014A patent/TWI293627B/zh active
- 2004-10-05 MY MYPI20044077A patent/MY143797A/en unknown
-
2006
- 2006-03-23 IL IL174513A patent/IL174513A/en active IP Right Grant
- 2006-03-31 NO NO20061469A patent/NO20061469L/no not_active Application Discontinuation
- 2006-04-05 ZA ZA200602802A patent/ZA200602802B/en unknown
- 2006-04-07 CO CO06034536A patent/CO5690560A2/es not_active Application Discontinuation
-
2015
- 2015-10-29 CY CY20151100963T patent/CY1116865T1/el unknown
- 2015-11-09 HR HRP20151197TT patent/HRP20151197T1/hr unknown
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| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] |
Free format text: NOTIFICACAO DE ANUENCIA RELACIONADA COM O ART 229 DA LPI |
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| B07A | Application suspended after technical examination (opinion) [chapter 7.1 patent gazette] | ||
| B06A | Patent application procedure suspended [chapter 6.1 patent gazette] | ||
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] | ||
| B16C | Correction of notification of the grant [chapter 16.3 patent gazette] |
Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 27/09/2004 OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF |