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 |
|---|---|---|---|
| EP03022650.0 | 2003-10-06 | ||
| EP03022650 | 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 |
| US7816387B2 (en) * | 2005-09-05 | 2010-10-19 | Dainippon Sumitomo Pharma Co., Ltd. | β secretase inhibitor |
| ES2398531T3 (es) * | 2006-03-27 | 2013-03-20 | F. Hoffmann-La Roche Ag | Derivados de malonamida como inhibidores de gamma secretasa |
| AU2007299129A1 (en) | 2006-09-20 | 2008-03-27 | F. Hoffmann-La Roche Ag | 4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine derivatives |
| US8278345B2 (en) | 2006-11-09 | 2012-10-02 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| ATE554085T1 (de) | 2006-11-30 | 2012-05-15 | Probiodrug Ag | Neue inhibitoren von glutaminylcyclase |
| KR101150574B1 (ko) | 2007-02-02 | 2012-05-30 | 에프. 호프만-라 로슈 아게 | 6-옥소-6,7-다이하이드로-5ｈ-다이벤조［ｂ,ｄ］아제핀-7-일 유도체 |
| JP5930573B2 (ja) | 2007-03-01 | 2016-06-15 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤の新規使用 |
| FR2913886B1 (fr) | 2007-03-22 | 2012-03-02 | Guerbet Sa | Utilisation de nanoparticules metalliques dans le diagnostique de la maladie d'alzheimer |
| EP2142514B1 (en) | 2007-04-18 | 2014-12-24 | Probiodrug AG | Thiourea derivatives as glutaminyl cyclase inhibitors |
| US7579464B2 (en) * | 2007-05-25 | 2009-08-25 | Hoffmann-La Roche Inc. | Process for preparation of enantiomerically pure compounds |
| JP5934645B2 (ja) | 2009-09-11 | 2016-06-15 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体 |
| 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 |
| NZ602312A (en) | 2010-03-10 | 2014-02-28 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
| WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
| US20130102538A1 (en) * | 2010-05-05 | 2013-04-25 | Amicus Therapeutics, Inc. | Method of treating alzheimer's disease using pharmacological chaperones to increase presenilin function and gamma-secretase activity |
| EP2686313B1 (en) | 2011-03-16 | 2016-02-03 | Probiodrug AG | Benzimidazole derivatives as inhibitors of glutaminyl cyclase |
| AR087107A1 (es) | 2011-07-27 | 2014-02-12 | Lilly Co Eli | Compuesto inhibidor de la señalizacion de la trayectoria notch |
| ES2751082T3 (es) * | 2015-10-30 | 2020-03-30 | Pipeline Therapeutics Inc | Compuestos de dibenzo azepina y su uso en el tratamiento de enfermedades y trastornos óticos |
| WO2018111926A2 (en) * | 2016-12-16 | 2018-06-21 | Inception 3, Inc. | Methods of treating cochlear synaptopathy |
| ES2812698T3 (es) | 2017-09-29 | 2021-03-18 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
| CN112236147A (zh) * | 2018-05-15 | 2021-01-15 | 百时美施贵宝公司 | 包含双氟烷基-1,4-苯并二氮杂*酮化合物的组合物和其使用方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9314981D0 (en) * | 1993-07-20 | 1993-09-01 | Glaxo Spa | Chemical compounds |
| WO2000038618A2 (en) * | 1998-12-24 | 2000-07-06 | Du Pont Pharmaceuticals Company | SUCCINOYLAMINO BENZODIAZEPINES AS INHIBITORS OF Aβ PROTEIN PRODUCTION |
| WO2001077086A1 (en) * | 2000-04-11 | 2001-10-18 | Dupont Pharmaceuticals Company | SUBSTITUTED LACTAMS AS INHIBITORS OF Aβ PROTEIN PRODUCTION |
| CN1386118A (zh) * | 2000-06-01 | 2002-12-18 | 布里斯托尔-迈尔斯斯奎布药品公司 | 作为Aβ蛋白产生抑制剂的被环状琥珀酸酯取代的内酰胺类化合物 |
| EP1592684B1 (en) | 2003-02-04 | 2008-07-30 | F. Hoffmann-La Roche Ag | Malonamide derivatives as gamma-secretase inhibitors |
| KR100838852B1 (ko) * | 2003-09-09 | 2008-06-16 | 에프. 호프만-라 로슈 아게 | 감마-세크리테이즈의 활성을 차단하는 말론아미드 유도체 |
-
2004
- 2004-09-27 SI SI200432267T patent/SI1673347T1/sl unknown
- 2004-09-27 RU RU2006115165/04A patent/RU2356895C2/ru not_active IP Right Cessation
- 2004-09-27 PL PL04787028T patent/PL1673347T3/pl unknown
- 2004-09-27 KR KR1020087003016A patent/KR100884872B1/ko not_active Expired - Lifetime
- 2004-09-27 NZ NZ546036A patent/NZ546036A/en unknown
- 2004-09-27 HU HUE04787028A patent/HUE025548T2/en unknown
- 2004-09-27 US US10/951,229 patent/US7166587B2/en not_active Expired - Lifetime
- 2004-09-27 JP JP2006530028A patent/JP4503607B2/ja not_active Expired - Lifetime
- 2004-09-27 HR HRP20151197TT patent/HRP20151197T1/hr unknown
- 2004-09-27 KR KR1020067006540A patent/KR100867035B1/ko not_active Expired - Lifetime
- 2004-09-27 BR BRPI0415070A patent/BRPI0415070B8/pt not_active IP Right Cessation
- 2004-09-27 ES ES04787028.2T patent/ES2548720T3/es not_active Expired - Lifetime
- 2004-09-27 AU AU2004283803A patent/AU2004283803B2/en not_active Expired
- 2004-09-27 PT PT47870282T patent/PT1673347E/pt unknown
- 2004-09-27 MX MXPA06003870A patent/MXPA06003870A/es active IP Right Grant
- 2004-09-27 CA CA2541470A patent/CA2541470C/en not_active Expired - Lifetime
- 2004-09-27 DK DK04787028.2T patent/DK1673347T3/en active
- 2004-09-27 CN CN2004800333748A patent/CN1894217B/zh not_active Expired - Lifetime
- 2004-09-27 EP EP04787028.2A patent/EP1673347B1/en not_active Expired - Lifetime
- 2004-09-27 WO PCT/EP2004/010821 patent/WO2005040126A1/en not_active Ceased
- 2004-10-04 TW TW093130014A patent/TWI293627B/zh active
- 2004-10-04 AR ARP040103592A patent/AR045859A1/es unknown
- 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
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| B07A | Application suspended after technical examination (opinion) [chapter 7.1 patent gazette] | ||
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| 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 |
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| B21F | Lapse acc. art. 78, item iv - on non-payment of the annual fees in time |
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| B24J | Lapse because of non-payment of annual fees (definitively: art 78 iv lpi, resolution 113/2013 art. 12) |
Free format text: EM VIRTUDE DA EXTINCAO PUBLICADA NA RPI 2846 DE 22-07-2025 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDA A EXTINCAO DA PATENTE E SEUS CERTIFICADOS, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013. |