MA28034A1 - Derives de malonamide bloquant l 'activite gama-secretase - Google Patents

Derives de malonamide bloquant l 'activite gama-secretase

Info

Publication number
MA28034A1
MA28034A1 MA28867A MA28867A MA28034A1 MA 28034 A1 MA28034 A1 MA 28034A1 MA 28867 A MA28867 A MA 28867A MA 28867 A MA28867 A MA 28867A MA 28034 A1 MA28034 A1 MA 28034A1
Authority
MA
Morocco
Prior art keywords
lower alkyl
halogen
hydrogen
cycloalkyl
phenyl
Prior art date
Application number
MA28867A
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 MA28034A1 publication Critical patent/MA28034A1/fr

Links

Classifications

    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/55131,4-Benzodiazepines, e.g. diazepam or clozapine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/557Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/558Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes
    • 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
    • C07D223/18Dibenzazepines; Hydrogenated dibenzazepines
    • C07D223/20Dibenz [b, e] azepines; Hydrogenated dibenz [b, e] azepines
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D273/00Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D313/00Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
    • C07D313/02Seven-membered rings
    • C07D313/06Seven-membered rings condensed with carbocyclic rings or ring systems
    • C07D313/10Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
    • C07D313/14[b,f]-condensed

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Pyrane Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

DERIVES DE MALONAMIDE BLOQUANT L'ACTIVITE DE LA GAMMA-SECRETASE L'invention concerne des dérivés de malonamide de formule (I), dans laquelle : R1 est un des groupes suivants (formules a) , b), c), d)) ; R2 est un radical alkyle inférieur, alcynyle inférieur, -(CH2)n-O-(alkyle inférieur), -(CH2)n-S-(alkyle inférieur), -(CH2)n-CN, - (CR¿R")n-CF3, - (CR'R")n-CHF2, -(CR'R")n-CH2F, -(CH2)n-C(O)O-(alkyle inférieur), -(CH2)n-halogéno ou est -(CH2)n-cycloalkyle, éventuellement substitué par un ou plusieurs substituants, choisis dans l'ensemble constitué par les halogènes et les radicaux phényle ou CF3 ; R',R" sont, indépendamment de n et l'un de l'autre, l'hydrogène, un radical alkyle inférieur, alcoxy inférieur, un halogène ou un radical hydroxy ; R3, R4 sont indépendamment l'un de l'autre l'hydrogène, un radical alkyle inférieur, alcoxy inférieur, phényle ou un halogène ; R5 est l'hydrogène, un radical alkyle inférieur, -(CH2)n-CF3 ou -(CH2)n-cycloalkyle ; R6 est l'hydrogène ou un halogène ; R7 est l'hydrogène ou un radical alkyle inférieur ; R8 est l'hydrogène, un radical alkyle inférieur, alcynyle inférieur, (CH2)n-CF3, -(CH2)n-cycloalkyle ou -(CH2)n-phényle, éventuellement substitué par un halogène ; R9 est l'hydrogène, un radical alkyle inférieur, -C(O)H, (C(O)-(alkyle inférieur), -C(O)-CF3, -C(O)-CH2F, -C(O)-CHF2, -C(O)-cycloalkyle, -C(O)-(CH2)n-O-(alkyle inférieur), -C(O)O- (CH2)n-cycloalkyle, -C(O)-phényle, éventuellement substitué par un ou plusieurs substituants choisis dans l'ensemble constitué d'un halogène ou de -C(O)O-(alkyle inférieur), ou est -S(O)2-(alkyle inférieur), (S(O)2-CF3, -(CH2)n-cycloalkyle ou est -(CH2)n-phényle, éventuellement substitué par un halogène ; n est 0, 1, 2, 3 ou 4 ; et des sels d'addition d'acide acceptables d'un point de vue pharmaceutique, des énantiomères optiquement; purs, des racémates ou un mélange diastéréoisomérique de ceux-ci. Ces composés peuvent être utilisés pour le traitement d'une maladie d'Alzheimer.
MA28867A 2003-09-09 2006-03-10 Derives de malonamide bloquant l 'activite gama-secretase MA28034A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP03019683 2003-09-09

Publications (1)

Publication Number Publication Date
MA28034A1 true MA28034A1 (fr) 2006-07-03

Family

ID=34224068

Family Applications (1)

Application Number Title Priority Date Filing Date
MA28867A MA28034A1 (fr) 2003-09-09 2006-03-10 Derives de malonamide bloquant l 'activite gama-secretase

Country Status (34)

Country Link
US (1) US7160875B2 (fr)
EP (1) EP1711470B1 (fr)
JP (2) JP4571639B2 (fr)
KR (3) KR100838852B1 (fr)
CN (1) CN100593539C (fr)
AR (1) AR045609A1 (fr)
AT (1) ATE428698T1 (fr)
AU (1) AU2004270361B2 (fr)
BR (1) BRPI0413533A (fr)
CA (1) CA2537440C (fr)
CO (1) CO5660268A2 (fr)
CR (1) CR8264A (fr)
CY (1) CY1109225T1 (fr)
DE (1) DE602004020680D1 (fr)
DK (1) DK1711470T3 (fr)
EA (1) EA009940B1 (fr)
EC (1) ECSP066414A (fr)
ES (1) ES2322652T3 (fr)
HR (1) HRP20090266T1 (fr)
IL (1) IL173905A (fr)
MA (1) MA28034A1 (fr)
MX (1) MXPA06002562A (fr)
MY (1) MY141308A (fr)
NO (1) NO20061047L (fr)
NZ (1) NZ545538A (fr)
PL (1) PL1711470T3 (fr)
PT (1) PT1711470E (fr)
RS (1) RS20060146A (fr)
SI (1) SI1711470T1 (fr)
TN (1) TNSN06077A1 (fr)
TW (1) TW200519092A (fr)
UA (1) UA83501C2 (fr)
WO (1) WO2005023772A1 (fr)
ZA (1) ZA200601989B (fr)

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EP1592684B1 (fr) * 2003-02-04 2008-07-30 F. Hoffmann-La Roche Ag Derives de malonamide utilises comme inhibiteurs de la gamma-secretase
KR100838852B1 (ko) * 2003-09-09 2008-06-16 에프. 호프만-라 로슈 아게 감마-세크리테이즈의 활성을 차단하는 말론아미드 유도체
SI1673347T1 (sl) * 2003-10-06 2015-10-30 F. Hoffmann - La Roche Ag Substituirani derivati dibenzo-azepina in benzo-diazepina, ki so uporabni kot inhibitorji gama-sekretaze
US7211573B2 (en) * 2004-12-08 2007-05-01 Hoffmann-La Roche Inc. Malonamide derivatives
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
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
CN101636378A (zh) * 2007-03-15 2010-01-27 弗·哈夫曼-拉罗切有限公司 作为食欲肽拮抗剂的丙二酰胺类
US7579464B2 (en) * 2007-05-25 2009-08-25 Hoffmann-La Roche Inc. Process for preparation of enantiomerically pure compounds
US8741889B2 (en) 2008-01-11 2014-06-03 Hoffmann-La Roche Inc Method of treating non-small cell lung cancer and colon cancer with gamma-secretase inhibitor
MA33076B1 (fr) * 2008-01-11 2012-03-01 Hoffmann La Roche Utilisation d'un inhibiteur de la gamma-secretase pour le traitement du cancer
US8309299B2 (en) * 2010-05-19 2012-11-13 Hoffmann-La Roche Inc. Combination therapy and method for assessing resistance to treatment
WO2012040444A2 (fr) * 2010-09-24 2012-03-29 Bristol-Myers Squibb Company Traitement de patients présentant un début de maladie d'alzheimer
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KR101330184B1 (ko) 2010-10-15 2013-11-15 성균관대학교산학협력단 감마-세크레타제 저해제를 유효성분으로 함유하는 류마티스성 관절염의 예방 또는 치료용 조성물
US20120114638A1 (en) 2010-11-08 2012-05-10 John Boylan Combination therapy
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US20120225860A1 (en) 2011-03-02 2012-09-06 John Frederick Boylan Method for administration of a gamma secretase inhibitor
TWI530489B (zh) 2011-03-22 2016-04-21 必治妥美雅史谷比公司 雙(氟烷基)-1,4-苯二氮呯酮化合物
AR087107A1 (es) 2011-07-27 2014-02-12 Lilly Co Eli Compuesto inhibidor de la señalizacion de la trayectoria notch
JP2015531792A (ja) 2012-09-21 2015-11-05 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company 1,4−ベンゾジアゼピノン化合物のプロドラッグ
EP2897942B1 (fr) 2012-09-21 2016-08-31 Bristol-Myers Squibb Company Composés de fluoralkyl- et de fluorocycloalkyl-1,4-benzodiazépinone utilisables en tant qu'inhibiteurs du récepteur notch
US9242940B2 (en) 2012-09-21 2016-01-26 Bristol-Myers Squibb Company N-substituted bis(fluoroalkyl)-1,4-benzodiazepinone compounds
CN104797584A (zh) 2012-09-21 2015-07-22 百时美施贵宝公司 作为notch抑制剂的三环杂环化合物
WO2014047370A1 (fr) 2012-09-21 2014-03-27 Bristol-Myers Squibb Company Composés fluoroalkyl benzodiazépinones
TWI614238B (zh) 2012-09-21 2018-02-11 必治妥美雅史谷比公司 雙(氟烷基)-1,4-苯并二氮呯酮化合物及其前藥
CN105308030A (zh) 2012-09-21 2016-02-03 百时美施贵宝公司 烷基、氟烷基-1,4-苯并二氮杂*酮化合物
CN104797569A (zh) 2012-09-21 2015-07-22 百时美施贵宝公司 取代的1,5-苯并二氮杂*酮化合物
WO2014047392A1 (fr) 2012-09-21 2014-03-27 Bristol-Myers Squibb Company Composés fluoroalkyl-1,4-benzodiazépinones
EP2981267A1 (fr) 2013-04-04 2016-02-10 Bristol-Myers Squibb Company Traitement combiné pour le traitement de maladies prolifératives
EP2932966A1 (fr) 2014-04-16 2015-10-21 Novartis AG Inhibiteurs de la gamma sécrétase pour traiter des maladies respiratoires
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 (fr) * 2016-12-16 2018-06-21 Inception 3, Inc. Méthodes de traitement de la synaptopathie cochléaire
EP3615055A1 (fr) 2017-04-28 2020-03-04 Novartis AG Cellules exprimant un récepteur antigénique chimérique ciblant le bcma, et polythérapie comprenant un inhibiteur de gamma sécrétase
US20200179511A1 (en) 2017-04-28 2020-06-11 Novartis Ag Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor
WO2019034532A1 (fr) * 2017-08-15 2019-02-21 Bayer Aktiengesellschaft 4-oxo-2,3,4,5-tétrahydro-1h-1,5-benzodiazépine-7-carboxamides
KR102870868B1 (ko) 2018-06-01 2025-10-15 노파르티스 아게 Bcma에 대한 결합 분자 및 이의 용도
CN119679936A (zh) 2019-06-24 2025-03-25 诺华股份有限公司 针对靶向b细胞成熟抗原的多特异性抗体的给药方案和组合疗法
WO2022020658A1 (fr) * 2020-07-23 2022-01-27 Purdue Research Foundation Inhibiteurs de signalisation de notch pour le traitement de l'obésité et de troubles métaboliques
US20240400531A1 (en) * 2021-08-31 2024-12-05 Basf Se Herbicidal malonamides containing a condensed ring system
WO2024096358A1 (fr) 2022-11-04 2024-05-10 주식회사 엘지화학 Support d'enregistrement d'hologramme et élément optique le comprenant
CN116621721B (zh) * 2023-04-12 2025-03-18 珠海市柏瑞医药科技有限公司 一种壬二酰胺的制备方法

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Also Published As

Publication number Publication date
TW200519092A (en) 2005-06-16
EA200600503A1 (ru) 2006-08-25
KR20060054455A (ko) 2006-05-22
NZ545538A (en) 2008-12-24
EP1711470A1 (fr) 2006-10-18
CO5660268A2 (es) 2006-07-31
PL1711470T3 (pl) 2009-09-30
US7160875B2 (en) 2007-01-09
CN100593539C (zh) 2010-03-10
JP4571639B2 (ja) 2010-10-27
HK1099014A1 (zh) 2007-08-03
AR045609A1 (es) 2005-11-02
JP2010229153A (ja) 2010-10-14
DE602004020680D1 (de) 2009-05-28
KR100838852B1 (ko) 2008-06-16
ZA200601989B (en) 2007-05-30
HRP20090266T1 (en) 2009-06-30
ATE428698T1 (de) 2009-05-15
PT1711470E (pt) 2009-05-21
CN1875005A (zh) 2006-12-06
ECSP066414A (es) 2006-09-18
IL173905A (en) 2011-05-31
MY141308A (en) 2010-04-16
AU2004270361B2 (en) 2009-06-25
EA009940B1 (ru) 2008-04-28
EP1711470B1 (fr) 2009-04-15
RS20060146A (sr) 2008-06-05
NO20061047L (no) 2006-04-04
AU2004270361A1 (en) 2005-03-17
WO2005023772A1 (fr) 2005-03-17
ES2322652T3 (es) 2009-06-24
KR20070087690A (ko) 2007-08-28
BRPI0413533A (pt) 2006-10-10
SI1711470T1 (sl) 2009-08-31
KR20070087233A (ko) 2007-08-27
JP2007505063A (ja) 2007-03-08
TNSN06077A1 (fr) 2007-10-03
US20050054633A1 (en) 2005-03-10
CR8264A (es) 2008-09-22
IL173905A0 (en) 2006-07-05
KR100834177B1 (ko) 2008-05-30
UA83501C2 (uk) 2008-07-25
MXPA06002562A (es) 2006-06-20
CA2537440A1 (fr) 2005-03-17
CY1109225T1 (el) 2014-07-02
CA2537440C (fr) 2012-07-10
DK1711470T3 (da) 2009-06-08

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