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PE20060692A1 - Inhibidores bace - Google Patents

Inhibidores bace

Info

Publication number
PE20060692A1
PE20060692A1 PE2005001080A PE2005001080A PE20060692A1 PE 20060692 A1 PE20060692 A1 PE 20060692A1 PE 2005001080 A PE2005001080 A PE 2005001080A PE 2005001080 A PE2005001080 A PE 2005001080A PE 20060692 A1 PE20060692 A1 PE 20060692A1
Authority
PE
Peru
Prior art keywords
alkyl
benzyl
cycloalkyl
carboxyl
refers
Prior art date
Application number
PE2005001080A
Other languages
English (en)
Inventor
Timothy Barrett Durham
Patric James Hahn
James Ray Mccarthy
Robert Dean Dally
Timothy Alan Shepherd
Maria Rosario Gonzales-Garcia
Kenneth James Henry Jr
Howard Barff Broughton
Todd Jonathan Kohn
Original Assignee
Lilly Co Eli
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 Lilly Co Eli filed Critical Lilly Co Eli
Publication of PE20060692A1 publication Critical patent/PE20060692A1/es

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06Esters of carbamic acids
    • C07C271/08Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/20Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
    • 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
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00Carboxylic acid amides
    • C07C233/01Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/34Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
    • C07C233/35Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/36Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D265/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/281,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/301,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D265/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/281,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/301,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • C07D265/321,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02Silicon compounds
    • C07F7/08Compounds having one or more C—Si linkages
    • C07F7/18Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804Compounds having Si-O-C linkages
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00Systems containing only non-condensed rings
    • C07C2601/06Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00Systems containing only non-condensed rings
    • C07C2601/12Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14The ring being saturated
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00Systems containing only non-condensed rings
    • C07C2601/18Systems containing only non-condensed rings with a ring being at least seven-membered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00Systems containing at least three condensed rings
    • C07C2603/56Ring systems containing bridged rings
    • C07C2603/58Ring systems containing bridged rings containing three rings
    • C07C2603/70Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74Adamantanes

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Steroid Compounds (AREA)

Abstract

SE REFIERE A UN COMPUESTO DE FORMULA I, DONDE R1 ES ALQUILO C1-C8, ALQUENILO C2-C8, ALQUINILO C2-C8, CICLOALQUILO C3-C8, ENTRE OTROS; R2 ES ALQUILO C1-C3, BENCILO, BENCILO DISUSTITUIDO, BENCILO TRISUSTITUIDO, ENTRE OTROS; R3 ES H, ALQUILO C1-C6 SUSTITUIDO O NO CON CICLOALQUILO C3-C8, 1-3 FLUOR; R4 ES H, ALQUILO C1-C6 O R3 Y R4 JUNTO AL CARBONO AL QUE ESTAN UNIDOS FORMAN UN ANILLO CICLOALQUILO C3-C6; R5 ES H, ALQUILO C1-C10 SUSTITUIDO O NO, ENTRE OTROS; R6 ES H, FENILO; G ES O, S(O)0-2. SON COMPUESTOS PREFERIDOS: ESTER TERC-BUTILICO DEL ACIDO (2R,5R)-5-[(1S,2S)-2-ACETILAMINO-1-BENCILOXI-3-(3,5-DIFLUOROFENIL)PROPIL]-2-ISOBUTOXIMORFOLINA-4-CARBOXILICO; ESTER TERC-BUTILICO DEL ACIDO (2S,5R)-5-[(1S,2S)-2-ACETILAMINO-3-(3,5-DUFLUOROFENIL)-1-HIDROXIPROPIL]-2-(3-METILBUTOXI)MORFOLINA-4-CARBOXILICO; ENTRE OTROS. SE REFIERE TAMBIEN A UNA COMPOSICION FARMACEUTICA Y A UN PROCEDIMIENTO DE PREPARACION. DICHOS COMPUESTOS SON INHIBIDORES DE LA ENZIMA DE ESCISION DE LA PROTEINA PRECURSORA AMILOIDE DE SITIO BETA (BACE) UTILES EN EL TRATAMIENTO O PREVENCION DE ALZHEIMER
PE2005001080A 2004-09-21 2005-09-19 Inhibidores bace PE20060692A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US61171804P 2004-09-21 2004-09-21
US69694905P 2005-07-06 2005-07-06

Publications (1)

Publication Number Publication Date
PE20060692A1 true PE20060692A1 (es) 2006-07-19

Family

ID=35976430

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2005001080A PE20060692A1 (es) 2004-09-21 2005-09-19 Inhibidores bace

Country Status (9)

Country Link
US (1) US7745438B2 (es)
EP (1) EP2091928A2 (es)
JP (1) JP2008513539A (es)
AR (1) AR051293A1 (es)
CA (1) CA2577799A1 (es)
PE (1) PE20060692A1 (es)
SV (1) SV2006002232A (es)
TW (1) TW200624426A (es)
WO (1) WO2006034093A2 (es)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7763609B2 (en) 2003-12-15 2010-07-27 Schering Corporation Heterocyclic aspartyl protease inhibitors
US7585885B2 (en) 2004-04-22 2009-09-08 Eli Lilly And Company Pyrrolidine derivatives useful as BACE inhibitors
EP1740575A2 (en) 2004-04-22 2007-01-10 Eli Lilly And Company Pyrrolidine derivatives useful as bace inhibitors
WO2008029825A1 (fr) 2006-09-05 2008-03-13 Kyowa Hakko Kirin Co., Ltd. Dérivé d'imidazole
UY32799A (es) 2009-07-24 2011-02-28 Novartis Ag Derivados de oxazina y su uso en el tratamiento de trastornos neurológicos
US8188079B2 (en) * 2009-08-19 2012-05-29 Hoffman-La Roche Inc. 3-amino-5-phenyl-5,6-dihydro-2H-[1,4]oxazines
EA021240B1 (ru) * 2010-06-09 2015-05-29 Янссен Фармацевтика Нв Производные 5,6-дигидро-2h-[1,4]оксазин-3-иламина в качестве ингибиторов бета-секретазы (bace)
AU2011278825B2 (en) 2010-07-13 2012-09-20 Novartis Ag Oxazine derivatives and their use in the treatment of neurological disorders
EA022409B1 (ru) 2010-12-22 2015-12-30 Янссен Фармацевтика Нв Производные 5,6-дигидроимидазо[1,2-а]пиразин-8-иламина, пригодные в качестве ингибиторов бета-секретазы (васе)
US8524897B2 (en) * 2011-01-12 2013-09-03 Novartis Ag Crystalline oxazine derivative
JP5715710B2 (ja) 2011-01-13 2015-05-13 ノバルティス アーゲー 新規複素環誘導体および神経障害の処置におけるそれらの使用
US9242943B2 (en) * 2011-01-18 2016-01-26 Siena Biotech S.P.A. 1,4 oxazines as BACE1 and/or BACE2 inhibitors
SI2681219T1 (sl) 2011-03-01 2016-02-29 Janssen Pharmaceutica, N.V. Derivati 6,7-dihidro-pirazolo(1,5-a)pirazin-4-ilamina uporabni kot inhibitorji beta-sekretaze (BACE)
ES2534973T3 (es) 2011-03-09 2015-04-30 Janssen Pharmaceutica N.V. Derivados de 3,4-dihidro-pirrolo[1,2-a]pirazin-1-ilamina útiles como inhibidores de beta-secretasa (BACE)
US9079919B2 (en) * 2011-05-27 2015-07-14 Hoffmann-La Roche Inc. Spiro-[1,3]-oxazines and spiro-[1,4]-oxazepines as BACE1 and/or BACE2 inhibitors
MX2013014007A (es) * 2011-06-07 2014-03-12 Hoffmann La Roche [1,3] oxazinas.
AU2012266544A1 (en) * 2011-06-07 2013-11-21 F. Hoffmann-La Roche Ag Halogen-alkyl-1,3 oxazines as BACE1 and/or BACE2 inhibitors
US8338413B1 (en) 2012-03-07 2012-12-25 Novartis Ag Oxazine derivatives and their use in the treatment of neurological disorders
ES2769578T3 (es) 2013-02-12 2020-06-26 Buck Inst Res Aging Hidantoínas que modulan el procesamiento de APP mediado por BACE
CN105283457B (zh) 2013-06-12 2018-09-18 詹森药业有限公司 作为β-分泌酶(BACE)抑制剂的4-氨基-6-苯基-5,6-二氢咪唑并[1,5-A]吡嗪衍生物
CN105324383B (zh) 2013-06-12 2017-10-31 詹森药业有限公司 作为β‑分泌酶(BACE)抑制剂的4‑氨基‑6‑苯基‑6,7‑二氢[1,2,3]三唑并[1,5‑A]吡嗪衍生物
WO2014198851A1 (en) 2013-06-12 2014-12-18 Janssen Pharmaceutica Nv 4-amino-6-phenyl-5,6-dihydroimidazo[1,5-a]pyrazin-3(2h)-one derivatives as inhibitors of beta-secretase (bace)
EP3078659B1 (en) * 2013-12-02 2017-11-15 Jenkem Technology Co., Ltd. (Beijing) 3-furyl-2-cyano-2-acrylamide derivative, preparation method therefor, pharmaceutical composition and use thereof
WO2016096979A1 (en) 2014-12-18 2016-06-23 Janssen Pharmaceutica Nv 2,3,4,5-tetrahydropyridin-6-amine and 3,4-dihydro-2h-pyrrol-5-amine compound inhibitors of beta-secretase

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0395664A1 (en) 1987-10-21 1990-11-07 The Upjohn Company Renin inhibitors containing a (1-amino-2-hydroxy-2-heterocyclic) ethyl moiety
BR0211122A (pt) * 2001-07-10 2004-10-26 Elan Pharm Inc Composto, métodos para o tratamento ou prevenção de doenças e para fabricar um composto, intermediário, e, uso de um composto ou sal
US6673821B2 (en) * 2001-10-22 2004-01-06 Enanta Pharmaceuticals, Inc. Nitrogen heterocycle inhibitors of aspartyl protease
UY27967A1 (es) * 2002-09-10 2004-05-31 Pfizer Acetil 2-hindroxi-1,3-diaminoalcanos
DE60329316D1 (de) 2002-11-12 2009-10-29 Merck & Co Inc Phenylcarboxamide als beta-sekretase-hemmer zur behandlung von alzheimer
JP4198086B2 (ja) 2003-06-25 2008-12-17 オリンパス株式会社 蛍光観察用装置
AU2004265298A1 (en) * 2003-08-08 2005-02-24 Pharmacopeia, Inc. Cyclic amine BACE-1 inhibitors having a benzamide substituent
EP1740575A2 (en) * 2004-04-22 2007-01-10 Eli Lilly And Company Pyrrolidine derivatives useful as bace inhibitors
US7388007B2 (en) * 2004-08-26 2008-06-17 Bristol-Myers Squibb Company Gamma-lactams as beta-secretase inhibitors

Also Published As

Publication number Publication date
WO2006034093A3 (en) 2006-07-13
WO2006034093A2 (en) 2006-03-30
TW200624426A (en) 2006-07-16
EP2091928A2 (en) 2009-08-26
SV2006002232A (es) 2006-05-25
US7745438B2 (en) 2010-06-29
US20070225267A1 (en) 2007-09-27
JP2008513539A (ja) 2008-05-01
AR051293A1 (es) 2007-01-03
CA2577799A1 (en) 2006-03-30

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