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-secretase

Info

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
Application number
BRPI0415070-8A
Other languages
English (en)
Inventor
Alexander Flohr
Guido Galley
Roland Jakob-Roetne
Eric Argirios Kitas
Jens-Uwe Peters
Wolfgang Wostl
Original Assignee
Hoffmann La Roche
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of BRPI0415070A publication Critical patent/BRPI0415070A/pt
Publication of BRPI0415070B1 publication Critical patent/BRPI0415070B1/pt
Publication of BRPI0415070B8 publication Critical patent/BRPI0415070B8/pt

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D223/00Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/16Benzazepines; Hydrogenated benzazepines
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D223/00Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/18Dibenzazepines; Hydrogenated dibenzazepines
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D243/00Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10Heterocyclic 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
    • C07D243/121,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D243/00Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10Heterocyclic 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
    • C07D243/141,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D243/00Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10Heterocyclic 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
    • C07D243/141,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/161,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/181,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C07D243/24Oxygen atoms

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  • 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.
BRPI0415070A 2003-10-06 2004-09-27 derivados de dibenzo-azepina e benzo-diazepina substituídos úteis, seu uso e seu processo de preparação, e medicamento BRPI0415070B8 (pt)

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)

* Cited by examiner, † Cited by third party
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
EP1942101A4 (en) * 2005-09-05 2010-08-25 Yoshiaki Kiso INHIBITOR OF -SECRETASE
RU2440342C2 (ru) * 2006-03-27 2012-01-20 Ф.Хоффманн-Ля Рош Аг МАЛОНАМИДНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ γ-СЕКРЕТАЗЫ
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
US9126987B2 (en) 2006-11-30 2015-09-08 Probiodrug Ag Inhibitors of glutaminyl cyclase
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.
AU2008220785B2 (en) 2007-03-01 2013-02-21 Vivoryon Therapeutics N.V. 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
PL2475428T3 (pl) 2009-09-11 2015-12-31 Probiodrug Ag Pochodne heterocykliczne jako inhibitory cyklazy glutaminowej
US9181233B2 (en) 2010-03-03 2015-11-10 Probiodrug Ag Inhibitors of glutaminyl cyclase
DK2545047T3 (da) 2010-03-10 2014-07-28 Probiodrug Ag Heterocycliske inhibitorer af glutaminylcyclase (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
RU2757276C2 (ru) * 2016-12-16 2021-10-12 Пайплайн Терапьютикс, Инк. Способы лечения кохлеарной синаптопатии
PL3461819T3 (pl) 2017-09-29 2020-11-30 Probiodrug Ag Inhibitory cyklazy glutaminylowej
AU2019271151A1 (en) * 2018-05-15 2021-01-07 Ayala Pharmaceuticals Inc. Compositions comprising bisfluoroalkyl-1,4-benzodiazepinone compounds and methods of use thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2347671A1 (en) * 1998-12-24 2000-07-06 Dupont Pharmaceuticals Company Succinoylamino benzodiazepines as inhibitors of a.beta. protein production
US6632812B2 (en) * 2000-04-11 2003-10-14 Dupont Pharmaceuticals Company Substituted lactams as inhibitors of Aβ protein production
AU783857B2 (en) * 2000-06-01 2005-12-15 Bristol-Myers Squibb Pharma Company Lactams substituted by cyclic succinates as inhibitors of a beta protein production
CA2514267C (en) * 2003-02-04 2011-05-17 F. Hoffmann-La Roche Ag Malonamide derivatives as gamma-secretase inhibitors
SI1711470T1 (sl) * 2003-09-09 2009-08-31 Hoffmann La Roche Derivati malonamida, ki blokirajo aktivnost gama-sekretaze

Also Published As

Publication number Publication date
KR100884872B1 (ko) 2009-02-23
CN1894217B (zh) 2011-09-21
PL1673347T3 (pl) 2016-01-29
TW200526586A (en) 2005-08-16
EP1673347A1 (en) 2006-06-28
CY1116865T1 (el) 2017-04-05
MY143797A (en) 2011-07-15
PT1673347E (pt) 2015-11-02
EP1673347B1 (en) 2015-08-19
CN1894217A (zh) 2007-01-10
KR20080016754A (ko) 2008-02-21
CO5690560A2 (es) 2006-10-31
IL174513A (en) 2011-12-29
AU2004283803B2 (en) 2010-06-24
RU2006115165A (ru) 2007-11-20
DK1673347T3 (en) 2015-10-12
BRPI0415070B8 (pt) 2021-05-25
BRPI0415070B1 (pt) 2018-05-15
HUE025548T2 (en) 2016-02-29
IL174513A0 (en) 2006-08-01
AR045859A1 (es) 2005-11-16
KR100867035B1 (ko) 2008-11-04
AU2004283803A1 (en) 2005-05-06
MXPA06003870A (es) 2006-07-03
NO20061469L (no) 2006-06-26
CA2541470A1 (en) 2005-05-06
WO2005040126A1 (en) 2005-05-06
ES2548720T3 (es) 2015-10-20
ZA200602802B (en) 2007-09-26
NZ546036A (en) 2009-10-30
SI1673347T1 (sl) 2015-10-30
RU2356895C2 (ru) 2009-05-27
KR20060085632A (ko) 2006-07-27
CA2541470C (en) 2011-11-29
US7166587B2 (en) 2007-01-23
JP4503607B2 (ja) 2010-07-14
HRP20151197T1 (hr) 2015-12-04
JP2007507447A (ja) 2007-03-29
TWI293627B (en) 2008-02-21
US20050075327A1 (en) 2005-04-07

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B06F Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]
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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]
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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