AR041440A1 - Lactamicos y sus usos - Google Patents

Lactamicos y sus usos

Info

Publication number
AR041440A1
AR041440A1 ARP030103560A ARP030103560A AR041440A1 AR 041440 A1 AR041440 A1 AR 041440A1 AR P030103560 A ARP030103560 A AR P030103560A AR P030103560 A ARP030103560 A AR P030103560A AR 041440 A1 AR041440 A1 AR 041440A1
Authority
AR
Argentina
Prior art keywords
alkyl
oxygen
nitrogen
occurrence
independently selected
Prior art date
Application number
ARP030103560A
Other languages
English (en)
Original Assignee
Astrazeneca Ab
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
Priority claimed from SE0202929A external-priority patent/SE0202929D0/xx
Priority claimed from SE0203829A external-priority patent/SE0203829D0/xx
Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab
Publication of AR041440A1 publication Critical patent/AR041440A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • 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
    • C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D267/02—Seven-membered rings
    • C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D267/10—Seven-membered rings having the hetero atoms in positions 1 and 4 not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D267/02—Seven-membered rings
    • C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D267/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D267/14—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D281/02—Seven-membered rings
    • C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D281/06—Seven-membered rings having the hetero atoms in positions 1 and 4 not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D281/02—Seven-membered rings
    • C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

Compuestos lactámicos y composiciones farmacéuticas que contienen dichos compuestos, y métodos para su uso en el tratamiento de trastornos neurológicos relacionados con la producción de proteína beta-amiloide y trastornos neurológicos tales como la enfermedad de Alzheimer. Estos compuestos inhiben la secretasa gama, por lo cual inhiben la producción de proteína beta-amiloide, y actúan de esa manera para prevenir la formación de depósitos neurológicos de proteína amiloide. Reivindicación 1: Un compuesto de fórmula (1), en donde: X es C, O, NR1, SO2 o S; Ar1 es un anillo de 5 ó 6 miembros, aromático o heterocíclico, opcionalmente sustituido con 0, 1, 2, ó 3 porciones Re, en donde dicho anillo tiene 0, 1, 2, ó 3 átomos de nitrógeno, oxígeno o azufre, pero no más de 2 átomos de oxígeno, ó 2 átomos de azufre ó 1 átomo de oxígeno y 1 átomo de azufre; R1 es H, alquilo(C1-3)cicloalquilo(C3-6), alquilo C1-6, alquenilo C3-6, alquinilo C3-6, cicloalquilo C3-6, alquilo (C2-4)NRaRb, alquilo (C1-4)C(=O)Rd; o alquilfenilo C1-3 sustituido con 0, 1, 2 ó 3 Re; Ra y Rb en cada aparición, se seleccionan en forma independiente, entre H, alquilo C1-4, o cicloalquilo C3-6, o Ra y Rb y el N al cual están unidos en combinación forman un heterociclo ligado a N de 5 ó 6 miembros, que tiene 2 átomos de nitrógeno, en donde el nitrógeno no ligado está sustituido con Rc, ó 1 átomo de anillo de nitrógeno y 1 de oxígeno, en donde no hay nitrógeno no ligado; Rc, en cada aparición se selecciona en forma independiente entre H, alquilo C1-3 o fenilo sustituido con 0, 1, 2 ó 3 Re; Rd , en cada aparición se selecciona en forma independiente entre alquilo C1-3, hidroxi, alcoxi C1-3 o NRaRb; Re, en cada aparición se selecciona de manera independiente entre H, OH, F, Cl, Br, I, CN, NO2, CF3, alquilo C1-6 o alcoxi C1-6; R2 y R3, en cada aparición, se seleccionan en forma independiente entre H, alquilo C1-6, cicloalquilo C4-6, arilo o heteroarilo, o R2 y R3 en combinación forman una porción fenilo o ciclohexilo fusionado que puede estar sustituido con 0, 1 ó 2 porciones Rf; Rf es NO2, F, Cl, Br, I, CF3, CN, alquilo C1-6 o alcoxi C1-6; R4 es H, CHR7R8, cicloalquilo de 5 ó 6 miembros, anillo heterocíclico de 5 ó 6 miembros, aromático de 5 ó 6 miembros opcionalmente con 0, 1 ó 2 porciones Rf, en donde dicho anillo heterocíclico tiene 0, 1, 2 ó 3 átomos de nitrógeno, oxígeno o azufre, pero no más de 2 átomos de oxígeno ó 2 átomos de azufre ó 1 átomo de oxígeno y 1 átomo de azufre; R5 es alquilo (C1-3)R9 o CH(OH)R10; R7 y R8, en cada aparición, se seleccionan en forma independiente entre H, alquilo C1-4, OH, SH, CH2SCH3, CONH2, CH2CONH2, CO2H, CH2CO2H, (CH2)3NHCH(NH2)2, alquilamina C1-4, indol, imidazol, fenilo o hidroxifenilo, o R7 y R8 en combinación forman un anillo heterocíclico o aromático de 6 miembros opcionalmente sustituido con 0, 1 ó 2 porciones Rf; dicho anillo heterocíclico tiene 0, 1, 2 ó 3 átomos de nitrógeno, oxígeno o azufre, pero no más de 2 átomos de oxígeno ó 2 átomos de azufre, ó 1 átomo de oxígeno y 1 átomo de azufre; R9 es fenilo sustituido con 0, 1, 2 ó 3 Re; R10 es alquilo o R9; o una sal farmacéuticamente aceptables de dicho compuesto.
ARP030103560A 2002-10-03 2003-09-30 Lactamicos y sus usos AR041440A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0202929A SE0202929D0 (sv) 2002-10-03 2002-10-03 Novel benzothiazepines and uses thereof
SE0203829A SE0203829D0 (sv) 2002-12-18 2002-12-18 Novel lactams and uses thereof

Publications (1)

Publication Number Publication Date
AR041440A1 true AR041440A1 (es) 2005-05-18

Family

ID=32072595

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP030103560A AR041440A1 (es) 2002-10-03 2003-09-30 Lactamicos y sus usos

Country Status (12)

Country Link
US (3) US7294622B2 (es)
EP (2) EP1845089A1 (es)
JP (2) JP4637584B2 (es)
AR (1) AR041440A1 (es)
AT (1) ATE374187T1 (es)
AU (1) AU2003265202A1 (es)
DE (1) DE60316588T2 (es)
DK (1) DK1554250T3 (es)
ES (1) ES2291743T3 (es)
PT (1) PT1554250E (es)
TW (1) TW200502221A (es)
WO (1) WO2004031154A1 (es)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7342007B2 (en) 2003-03-14 2008-03-11 Astrazeneca Ab Lactams and uses thereof
US7211573B2 (en) * 2004-12-08 2007-05-01 Hoffmann-La Roche Inc. Malonamide derivatives
US20080311609A1 (en) * 2004-12-14 2008-12-18 Astrazeneca Ab Novel Molecular Probes
GB2423085C (en) * 2005-02-11 2011-11-09 Cambridge Entpr Ltd Ligands for G-protein coupled receptors
ES2476027T3 (es) * 2005-10-25 2014-07-11 Shionogi & Co., Ltd. Derivados de aminodihidrotriazina
WO2007104933A1 (en) * 2006-03-10 2007-09-20 Astrazeneca Ab Chemical compounds
RU2440342C2 (ru) * 2006-03-27 2012-01-20 Ф.Хоффманн-Ля Рош Аг МАЛОНАМИДНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ γ-СЕКРЕТАЗЫ
CA2652669A1 (en) * 2006-06-09 2007-12-21 Merck & Co., Inc. Benzazepinones as sodium channel blockers
WO2008043031A1 (en) * 2006-10-04 2008-04-10 Pharmacopeia, Inc. 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression
ES2476605T3 (es) 2007-04-24 2014-07-15 Shionogi & Co., Ltd. Derivados de aminohidrotiazina sustituidos con grupos cíclicos
WO2008133273A1 (ja) 2007-04-24 2008-11-06 Shionogi & Co., Ltd. アルツハイマー症治療用医薬組成物
EA017286B1 (ru) * 2007-08-14 2012-11-30 Эли Лилли Энд Компани Ингибиторы гамма-секретазы
AU2009258496B8 (en) 2008-06-13 2014-06-26 Shionogi & Co., Ltd. Sulfur-containing heterocyclic derivative having beta-secretase-inhibiting activity
JPWO2010047372A1 (ja) 2008-10-22 2012-03-22 塩野義製薬株式会社 Ｂａｃｅ１阻害活性を有する２−アミノピリミジン−４−オンおよび２−アミノピリジン誘導体
CN101735211B (zh) * 2008-11-04 2012-11-14 复旦大学 2,3-二氢[1,5]苯并噻氮杂*类化合物或其盐在制备GSK-3β抑制剂中的用途
US9023767B2 (en) * 2009-05-07 2015-05-05 Memorial Sloan-Kettering Cancer Center γ-Secretase substrates and methods of use
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US8999980B2 (en) 2009-12-11 2015-04-07 Shionogi & Co., Ltd. Oxazine derivatives
CN103502466A (zh) 2010-09-07 2014-01-08 斯隆－凯特林纪念癌症中心 用于γ-分泌酶测定的方法和组合物
JP2014001142A (ja) * 2010-10-05 2014-01-09 Astellas Pharma Inc シクロアルカン化合物
EP2625170A1 (en) * 2010-10-07 2013-08-14 Takeda Pharmaceutical Company Limited 1,4-oxazepane derivatives
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US20080311609A1 (en) * 2004-12-14 2008-12-18 Astrazeneca Ab Novel Molecular Probes

Also Published As

Publication number Publication date
TW200502221A (en) 2005-01-16
EP1554250B1 (en) 2007-09-26
AU2003265202A1 (en) 2004-04-23
DE60316588D1 (de) 2007-11-08
EP1554250A1 (en) 2005-07-20
ATE374187T1 (de) 2007-10-15
ES2291743T3 (es) 2008-03-01
DE60316588T2 (de) 2008-07-31
US20060089346A1 (en) 2006-04-27
US7858776B2 (en) 2010-12-28
WO2004031154A1 (en) 2004-04-15
US20080076752A1 (en) 2008-03-27
JP4637584B2 (ja) 2011-02-23
JP2006503862A (ja) 2006-02-02
JP2010248216A (ja) 2010-11-04
US7294622B2 (en) 2007-11-13
US20100160627A1 (en) 2010-06-24
DK1554250T3 (da) 2007-12-17
EP1845089A1 (en) 2007-10-17
PT1554250E (pt) 2007-11-15

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