DK2406240T3 - Inhibitorer af beta-sekretase - Google Patents

Inhibitorer af beta-sekretase Download PDF

Info

Publication number
DK2406240T3
DK2406240T3 DK10708684.5T DK10708684T DK2406240T3 DK 2406240 T3 DK2406240 T3 DK 2406240T3 DK 10708684 T DK10708684 T DK 10708684T DK 2406240 T3 DK2406240 T3 DK 2406240T3
Authority
DK
Denmark
Prior art keywords
alkyl
alkoxy
halo
compound
cycloalkyl
Prior art date
Application number
DK10708684.5T
Other languages
English (en)
Inventor
Salvacion Cacatian
David A Claremon
Lawrence W Dillard
Klaus Fuchs
Niklas Heine
Katerina Leftheris
Brian Mckeever
Angel Morales-Ramos
Suresh Singh
Shankar Venkatraman
Guosheng Wu
Zhongren Wu
Jing Yuan
Yajun Zheng
Zhenrong Xu
Lanqi Jia
Original Assignee
Vitae Pharmaceuticals Inc
Boehringer Ingelheim Int
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 Vitae Pharmaceuticals Inc, Boehringer Ingelheim Int filed Critical Vitae Pharmaceuticals Inc
Application granted granted Critical
Publication of DK2406240T3 publication Critical patent/DK2406240T3/da

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/44—Nitrogen atoms not forming part of a nitro radical
    • C07D233/46—Nitrogen atoms not forming part of a nitro radical with only hydrogen atoms attached to said nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/04—1,3-Thiazines; Hydrogenated 1,3-thiazines
    • C07D279/08—1,3-Thiazines; Hydrogenated 1,3-thiazines condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D405/06—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 linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D405/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D405/14—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 three or more hetero rings
    • 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
    • C07D409/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/06—Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D417/04—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 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
    • C07D417/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D417/10—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 carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
    • C07D493/20—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/10—Spiro-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Epidemiology (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (25)

1. Forbindelse repræsenteret af den følgende strukturformel:
eller et farmaceutisk acceptabelt salt deraf, hvor: X er -O-, -CH2-, eller -CH2-CH2-; W er -N(Ri4)-, -S-,eller -O-; Z er -C( = 0)-, -C( = S)-, -C( = NRi5)-, -O-, -C( = 0)C(Ri6Ri7)-, -C(Ri6Ri7) C( = 0)-, -C( = S)C(RieRi7)-, C(RieRi7) C(=S)-, -N(Ris)-, -(CRi6Ri7)m-, -0-(CRi6Ri7)-, eller -(CRi6Ri7)- O—, forudsat at når W er -S- eller -O-, er Z ikke -0-; Ri er -H, -OH, -(Ci-C4)alkoxy, (Ci-C6)alkyl, aryl(Ci-Ce)alkyl, eller heteroaryl(Ci-C6)alkyl; hvor hvert alkyl, aryl og heteroaryl er eventuelt substitueret med 1 til 5 substituenter uafhængigt valgt fra halogen, -CN, -OH, (Ci-C4)alkyl, halo(Ci-C4)alkyl, (Ci-C3)alkoxy og halo(Ci-C3)alkoxy; hvert R2 er uafhængigt valgt fra a) -H, -halogen, -CN, -NO2, -ORs, -NReR7, -S(0)iRs, -NRiiS(0)iRs, -S(0)iNRi2Ri3, C(=0)0Rs, -0C(=0)0Rs, -C(=S)ORs, -0(C=S)Rs, -C(=0)NR12Ri3, -NRiiC(=0)R5, -C(=S)NRi2Ri3, -NRiiC(=S)R5, -NRii(C=0)0R5, -0(C=0)NRi2Ri3, -NRii(C=S)OR5, -0(C=S)NRi2Ri3, -NRii(C=0)NRi2Ri3, -NRii(C=S)NRi2Ri3, -C(=S)R5, og -C(=0)R5; og b) (Ci-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(Ci-C6)alkyl, (C3-C8)cycloalkyl(C2-C6)alkynyl, (C4-C8)cycloalkenyl, (C3-Cg)heterocycloalkyl, (C3-C9)heterocycloalkyl(Ci-C6)alkyl, (C3-C9)heterocycloalkyl(C2-C6)alkynyl, aryl, aryl(Ci-Ce)alkyl, aryl(C2-C6)alkynyl, heteroaryl, heteroaryl(Ci-C6)alkyl, og heteroaryl(C2-Ce)alkynyl, hvor hver af (Ci-C6)alkyl. (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-Cejcycloalkyl, (C3-C8)cycloalkyl(C,-Cs)alkyl, (C3-C8)cycloalkyl(C2-C6)alkynyl, (C4-C8)cycloalkenyl, (C3-C9)heterocycloalkyl, (C3-C9)heterocycloalkyl(Ci-Ce)alkyl, (C3-C9)heterocycloalkyl(C2-C6)alkynyl, aryl, aryl(Ci-Ce)alkyl, aryl(C2-C6)alkynyl, heteroaryl, heteroaryl(Ci-C6)alkyl, og heteroaryl(C2-Ce)alkynyl -grupper repræsenteret af R2 er eventuelt substitueret med 1 til 5 substituenter uafhængigt valgt fra gruppen bestående af -halogen, -CN, -NO2, -ORs, -SRs, -NReRy, -S(0)iRs, -NRnS(=0)iR5, -S(0)iNRi2Ri3, -C(=0)0Rs, -0C(=0)Rs, -C(=S)ORs, -OC(=S)R5, -C(=0)NRi2Ri3, -NRiiC(=0)Rs, -C(=S)NRi2Ri3, -NRhC(=S)R5, -C(=0)Rs, -C(=S)Rs, -0C(=0)0Rs, -0(C=0)NRi2Ri3, -NRh(C=0)0R5, -NRii(C=S)OR5, -0(C=S)NRi2Ri3, -NRh(C=0)NRi2Ri3, -NRii(C=S)NRi2Ri3, -C(=0)Rs, -C(=S)R5, (Ci-C6)alkyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C4-Cejcycloalkenyl, (C3-C9)heterocycloalkyl, (C2-C6)alkenyl, halo(Ci-C6)alkyl, (Ci-C3)alkylsulfonylaminoalkyl, hydroxy(Ci-C6)alkyl, cyano(Ci-C6)alkyl, (Ci-C3)alkylcarbonylamino(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy, (Ci-C6)alkoxy(Ci-C3)alkyl, aryl og heteroaryl, hvor cycloalkyl, heterocycloalkyl, aryl og heteroaryl -grupperne i substituenterne på grupperne repræsenteret af R2 er hver eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra halogen, -CN, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C3)alkoxy(Ci-C6)alkyl; R5 er -H, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (C2-Ce)alkenyl, (C2-C6)alkynyl, (Ci-C3)alkoxy(Ci-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(Ci-C6)alkyl, (C3-C9)heterocycloalkyl, (C3-C9)heterocycloalkyl(Ci-C6)alkyl, aryl, aryl(Ci-Ce)alkyl, heteroaryl eller heteroaryl(Ci-Ce)alkyl, hver af alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl og heteroaryl i grupperne repræsenteret af Rs er eventuelt substitueret med 1 til 5 substituenter uafhængigt valgt fra gruppen bestående af halogen, =0, -NR6C(=NH)NR6R7, -C(=0)0Rc, -ORc, -SRc, -C(=0)NR6R7, -C(=0)Rc, -S(0)iRc, -N02, -CN, (Ci-Ce)alkyl, halo(Ci-C6)alkyl, (Ci-C3)alkoxy(Ci-C6)alkyl, (Ci-Cs)alkoxy, halo(Ci-C3)alkoxy og -NR6R7; Rc er -H, (Ci-C3)alkyl, halo(Ci-C3)alkyl eller (Ci-C3)alkoxy(Ci-C3)alkyl; Re og R7 er hver uafhængigt -H, (Ci-Ce)alkyl, hydroxy(Ci-C6)alkyl, halo(Ci-Ce)alkyl, (C3-C8) cycloalkyl. (C3-C8)cycloalkyl(Ci-C6)alkyl, (C3-Cgjheterocycloalkyl, (C3-C9)heterocycloalkyl(Ci-C6)alkyl, aryl, aryl(Ci-Ce)alkyl, heteroaryl, eller heteroaryl(Ci-Ce)alkyl, alle af hvilke grupper er eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af - halogen, -CN, (Ci-C6)alkyl, halo(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C3)alkoxy(Ci-Ce)alkyl; Rs og R9, sammen med kulstoffet til hvilket de er bundet, danner ring A, som er en 3-14-leddet monocyklisk ring, 9-14-leddet bicyklisk ring eller 9- 14-leddet polycyklisk ring, hvor ring A eventuelt indeholder 1 til 3 heteroatomer uafhængigt valgt fra O, N, og S og når heteroatomet er nitrogen, nitrogenet er substitueret med -H, (Ci-C3)alkyl eller halo(Ci-C3)alkyl, og når heteroatomet er svovl, svovlen er eventuelt mono eller di-oxygeneret; og ring A er eventuelt substitueret med 1 til 4 substituenter uafhængigt valgt fra gruppen bestående af halogen, -CN, -ORs, -NReR7, -S(0)iRs, -NRiiS(0)iR5, -S(0)iNRi2Ri3, -C( = 0)0R5, -0C( = 0)0Rs, -C( = S)OR5, -0(C=S)R5, -C( = 0)NRi2Ri3, -NRhC( = 0)R5, -C( = S)NRi2Ri3, -NRnC( = S)R5, -NRh(C=0)0R5, -0(C=0)NRi2Ri3, -NRh(C=S)OR5, -0(C=S)NRi2Ri3, -NRii(C=0)NRi2Ri3, -NRu(C=S)NRi2Ri3, -C( = S)Rs, -C( = 0)R5, (Ci-Ce)alkyl, (C2-Ce)alkenyl, halo(Ci-C6)alkyl, (Ci-C3)alkylsulfonylamino(Ci-C6)alkyl, hydroxy(Ci-Ce)alkyl, cyano(Ci-C6)alkyl, (Ci-C3)alkylcarbonylamino(Ci-Ce)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy, (Ci-C6)alkoxy(Ci-C3)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(Ci-C6)alkyl, (C3-C8)cycloalkyl(C2-C6)alkynyl, (C3-C9)heterocycloalkyl, (C3-C8)heterocycloalkyl(Ci-C6)alkyl, (C3-C9)heterocycloalkyl(C2-C6)alkynyl, aryl, aryl(Ci-C6)alkyl, aryl(C2-C6)alkynyl, heteroaryl, heteroaryl(Ci-C6)alkyl, og heteroaryl(C2-C6)alkynyl, hvor cycloalkyl, heterocycloalkyl, aryl og heteroaryl -grupperne i substituenterne på ring A er hver eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra halogen, -CN, (Ci-Ce)alkyl, halo(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C3)alkoxy(Ci-C6)alkyl; R11 er -H eller (Ci-Ce)alkyl, hvor (Ci-Ce)alkyl er eventuelt substitueret med 1 til 5 substituenter uafhængigt valgt fra halogen, CN, (Ci-Ce)alkoxy, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C3-C9)heterocycloalkyl, aryl og heteroaryl, hvor (Ci-Ce)alkoxy, (C2-Ce)alkynyl, (C3-C8)cycloalkyl, (C3-C9)heterocycloalkyl, aryl og heteroaryl -grupperne er hver eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af halogen, -CN, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C3)alkoxy(Ci-C6)alkyl; Ri2 og R13 er hver uafhængigt -H, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (Ci-C3)alkoxy(Ci-Ce)alkyl, hydroxy(Ci-Ce)alkyl, cyano(Ci-Ce)alkyl, amino(Ci-Ce)alkyl, (Ci-C3)alkylamino(Ci-C6)alkyl, di(Ci-C3)alkylamino(Ci-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(Ci-C6)alkyl, (C3-C9)heterocycloalkyl, (C3-C9)heterocycloalkyl(Ci-C6)alkyl, aryl, aryl(Ci-Ce)alkyl, heteroaryl eller heteroaryl(Ci-Ce)alkyl, hvor the (C3-Cs)cycloalkyl, (C3-C8)cycloalkyl(Ci- C6)alkyl, (C3-C9)heterocycloalkyl, (C3-C9)heterocycloalkyl(Ci-C6)alkyl, aryl, aryl(Ci-Ce)alkyl, heteroaryl og heteroaryl(Ci-C6)alkyl -gruppe er eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af halogen, -CN, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C3)alkoxy(Ci-Ce)alkyl; eller R12 og R13, sammen med nitrogenet til hvilket de er bundet, danner en 3-8-leddet ring eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af halogen, -CN, -ORs, -NReR7, -S(0)iRs, -S(0)iNRi2Ri3, -NRnS(0)iR5, -C( = 0)0Rs, -0C(=0)0Rs, -C(=S)ORs, -0(C=S)Rs, -C( = 0)NR6R7, -NRuC(=0)R5, -C(=S)NR6R7, -NRhC(=S)R5, -NRii(C=0)0Rs, -0(C=0)NR6R7, -NRn(C=S)ORs, -0(C=S)NR6R7, -NRn(C=0)NR6R7, -NRh(C=S)NR6R7, -C(=S)Rs, -C(=0)Rs, (Ci,-Ce)alkyl, (C2-Ce)alkenyl, halo(Ci-Ce)alkyl, (Ci-C3)alkylsulfonylaminoalkyl, hydroxy(Ci-C6)alkyl, cyano(Ci-C6)alkyl, (Ci-C3)alkylcarbonylamino(Ci-Ce)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C6)alkoxy(Ci-C3)alkyl, hvor den 3-8-leddede ring eventuelt indeholder til 3 yderligere heteroatomer, som er uafhængigt valgt fra O, N og S, hvor når det yderligere heteroatom er nitrogen, nitrogenet er substitueret med -H, (Ci-C3)alkyl eller halo(Ci-C3)alkyl, og når det yderligere heteroatom er svovl, svovlen er eventuelt mono eller di-oxygeneret; R14 er uafhængigt valgt fra -H, =0, =S, -NReR7, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(Ci-C3)alkyl, (C3-C9)heterocycloalkyl, (C3-C9)heterocycloalkyl(Ci-C3)alkyl, aryl, aryl(Ci-C6)alkyl, heteroaryl eller heteroaryl(Ci-Ce)alkyl, hver (Ci-Ce)alkyl, halo(Ci-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(Ci-C3)alkyl, (C3-Cg)heterocycloalkyl, (C3-C9)heterocycloalkyl(Ci-C3)alkyl, aryl, aryl(Ci-Ce)alkyl, heteroaryl eller heteroaryl(Ci-Ce)alkyl repræsenteret af R14 er eventuelt substitueret med 1 til 5 substituenter uafhængigt valgt fra gruppen bestående af-halogen, -CN, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (Ci-C3)alkoxy, -ORs, -NR6R7, -S(0)iR5, -S(0)iNRi2Ri3, -NRuS(0)iRs, -C( = 0)0Rs, -0C( = 0)0Rs, -C(=S)ORs, -0(C=S)Rs, -C( = 0)NRi2Ri3, -NRnC( = 0)Rs, -C( = S)NRi2Ri3, -NRuC( = S)Rs, -NRu(C=0)0Rs, -0(C=0)NRi2Ri3, -NRn(C=S)ORs, -0(C=S)NRi2Ri3, -NRn(C=0)NRi2Ri3, -NRii(C=S)NRi2Ri3, -C(=S)Rs og -C(=0)R5; Ris er -H eller (Ci-Ce)alkyl eventuelt substitueret med 1 til 5 -F; Ri6 og R17 er hver uafhængigt -H eller (Ci-C3)alkyl eventuelt substitueret med 1 til 5 -F; Rie er -H eller (Ci-C3)alkyl eventuelt substitueret med 1 til 5 -F; m er 1 eller 2; i er 0, 1 eller 2; og p er 1, 2, 3 eller 4.
2. Forbindelsen ifølge krav 1, hvor Z er -C( = 0)-, -C( = S)-, -C( = NRi5)-, -O-, -C( = 0)C(Ri6Ri7)-, -C( = S)C(Ri6Ri7)-, N(Ris)-, -(CRi6Ri7)m- eller -0-(CRi6Ri7)-, forudsat at når W er -S- eller -O-, er Z ikke - O-; Ri er -H, (Ci-Ce)alkyl, aryl(Ci-C6)alkyl, eller heteroaryl(Ci-C6)alkyl; hvert R2 er uafhængigt valgt fra a) -H, -halogen, -CN, -NO2, -ORs, -NR6R7, -S(0)iRs, -C(=0)0Rs, -C(=0)NRi2Ri3, og -C(=0)Rs; og b) (Ci-Ce)alkyl, (C2-C6)alkenyl, (C2-Ce)alkynyl, (C3-C8)cycloalkyl, aryl, heteroaryl, phenoxy, og benzyloxy, hver eventuelt substitueret med 1 til 3 substituenter valgt fra gruppen bestående af -F, -Cl, -Br, -CN, -ORs, -SRs, -NR6R7, -S(0)iRs, -NRuS(=0)iR5, -C(=0)0Rs, -C( = 0)NRi2Ri3, -NRhC( = 0)R5, -C( = S)NRi2Ri3, -C(=0)R5, (Ci-Ce)alkyl, (C3-C8)cycloalkyl, (C2-Ce)alkenyl, halo(Ci-Ce)alkyl, (Ci-C3)alkylsulfonylaminoalkyl, hydroxy(Ci-C6)alkyl, cyano(Ci-C6)alkyl, (Ci-C3)alkylcarbonylamino(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy, (Ci-C6)alkoxy(Ci-C3)alkyl, aryl og heteroaryl; R5 er -H, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (C2-Ce)alkenyl, (C2-Ce)alkynyl, (Ci-C3)alkoxy(Ci-Ce)alkyl, (C3-Cs)cycloalkyl, (C3-C8)cycloalkyl(Ci-C6)alkyl, (C3-C7) cycloheteroalkyl, aryl, heteroaryl eller benzyl, hver af hvilke er eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af -F, -Cl, -Br, -CN, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, og (Ci-C3)alkoxy(Ci-Ce)alkyl; Re og R7 er hver uafhængigt -H, (Ci-Ce)alkyl, hydroxy(Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(Ci-C6)alkyl, hver eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af -F, -Cl, -Br, -CN, (Ci-Ce)alkyl, halo(Ci-C6)alkyl og (Ci-C3)alkoxy(Ci-C6)alkyl; Re og Rg, sammen med kulstoffet til hvilket de er bundet, danner ring A, som er en 3-14-leddet monocyklisk ring, 9-14-leddet bicyklisk ring eller 9-14-leddet polycyklisk ring, hvor ring A er eventuelt substitueret med 1 til 4 substituenter uafhængigt valgt fra gruppen bestående af -F, -Cl, -Br, -CN, -ORs, -NReR7, -S(0)iRs, -NRnS(=0)iR5, -C(=0)0Rs, -C(=0)NRi2Ri3, -NRnC(=0)R5, - C(=S)NRi2Ri3, -C(=0)R5, (Ci-Ce)alkyl, (C2-Ce)alkenyl, halo(Ci-Ce)alkyl, (Ci-C3)alkylsulfonylaminoalkyl, hydroxy(Ci-C6)alkyl, cyano(Ci-Ce)alkyl, (Ci-C3)alkylcarbonylamino(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy, (Ci-C6)alkoxy(Ci-C3)alkyl, aryl og heteroaryl; Ru er -H, eller (Ci-Ce)alkyl, eventuelt substitueret med 1 til 3 uafhængigt valgt halogenatomer; R12 og R13 er hver uafhængigt -H, (Ci-Ce)alkyl, (Ci-C3)alkoxy(Ci-Ce)alkyl, hydroxy(Ci-Ce)alkyl, cyano(Ci-Ce)alkyl, amino(Ci-C6)alkyl, (Ci-C3)alkylamino(Ci-Ce)alkyl, eller di(Ci-C3)alkylamino(Ci-C6)alkyl; eller R12 og R13, sammen med nitrogenet til hvilket de er bundet, danner en 3-8-leddet ring eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af -F, -Cl, -Br, -CN, -ORs, -NReRy, -S(0)iRs, -NRnS(=0)iR5, -C(=0)0Rs, -C(=0)NR6R7, -NRhC(=0)R5, -C(=S)NR6R7, -C(=0)Rs, (Ci-Ce)alkyl, (C2-C6)alkenyl, halo(Ci-C6)alkyl, (Ci-C3)alkylsulfonylaminoalkyl, hydroxy(Ci-Ce)alkyl, cyano(Ci-Ce)alkyl, (Ci-C3)alkylcarbonylamino(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C6)alkoxy(Ci-C3)alkyl, hvor den 3-8-leddede ring eventuelt indeholder 1 til 3 yderligere heteroatomer, som er uafhængigt valgt fra O, N og S, hvor når det yderligere heteroatom er nitrogen, nitrogenet er substitueret med -H, (Ci-C3)alkyl eller halo(Ci-C3)alkyl, og når det yderligere heteroatom er svovl, svovlen er eventuelt mono eller di-oxygeneret; R14 er -H, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (C3-C8)cycloalkyl, (C3-C9)cycloheteroalkyl(Ci-C3)alkyl, (C3-C8)cycloalkyl(Ci-C3)alkyl, aryl(Ci-Ce)alkyl, heteroaryl(Ci-C6)alkyl, hver eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af -F, -Cl, -Br., -CN, (Ci-Ce)alkyl, halo(Ci-C6)alkyl og (Ci-C3)alkoxy; R15 er -H eller (Ci-Ce)alkyl; Ri6 og R17 er hver uafhængigt -H eller (Ci-C3)alkyl; Ris er -H eller (Ci-C3)alkyl; i er 0, 1 eller 2; og p er 1 eller 2.
3. Forbindelsen ifølge krav 1 eller krav 2, hvor forbindelsen er repræsenteret afen hvilken som helst af de følgende strukturformler:
eller
(XXIIa), eller et farmaceutisk acceptabelt salt deraf.
4. Forbindelsen ifølge krav 1 eller krav 2, hvor forbindelsen er repræsenteret afen hvilken som helst af de følgende strukturformler:
eller et farmaceutisk acceptabelt salt deraf.
5. Forbindelsen ifølge et hvilket som helst af kravene 1, 3 eller 4, hvor ring A er en 5-7-leddet monocyklisk ring eller en 9-14-leddet bicyklisk eller tricyklisk kondenseret ring eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af -F, -Cl, -Br, -CN, -ORs, -NReRy, -S(0)iRs, -NRiiS(=0)iRs, -C( = 0)0Rs, -C( = 0)NRi2Ri3, -NRhC(=0)R5, -C(=S)NRi2Ri3, -C(=0)Rs, (Ci-C6)alkyl, (C2-C6)alkenyl, halo(Ci-C6)alkyl, (Ci-C3)alkylsulfonylaminoalkyl, hydroxy(Ci-C6)alkyl, cyano(Ci-C6)alkyl, (Ci-C3)alkylcarbonylamino(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy, (Ci-C6)alkoxy(Ci-C3)alkyl, aryl og heteroaryl, hvor ring A indeholder 0 til 2 heteroatomer, som er uafhængigt valgt fra O, N og 5.
6. Forbindelsen ifølge krav 5, hvor ring A er valgt fra gruppen bestående af tetrahydrofuran, tetrahydropyran, cyclopentan, cyclohexan, cyclohexen, cycloheptan, oxepan, 1,3-dioxan, piperidin, 6,7,8,9-tetrahydro-5H-benzo[7]annulen, 2,3-dihydro-lH-inden, tetrahydronaphthalen, decahydronaphthalen, 5,6,7,8-tetrahydroquinolin, 5,6,7,8-tetrahydroisoquinolin, 2,3,4,5-tetrahydrobenzo[b]oxepin, og 2,3-dihydro-lH-phenalen, hver af hvilke er eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af-F, -Cl, -Br, -CN, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, hydroxy(Ci-Ce)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og phenyl, hvor phenyl er eventuelt substitueret med F, -Cl, -Br, -CN, (Ci-C6)alkyl, halo(Ci-C6)alkyl, (Ci-C3)alkoxy, og halo(Ci-C3)alkoxy.
7. Forbindelsen ifølge et hvilket som helst af kravene 1, 3, 4, 5 eller 6, hvor R2 er et pyridinyl, thiophenyl, pyrrolyl eller pyrimidinyl, hver eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af halogen, -CN, (Ci-Ce)alkyl, (C3-C8)cycloalkyl, halo(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C6)alkoxy(Ci-C3)alkyl.
8. Forbindelsen ifølge et hvilket som helst af kravene 1, 3, 5 eller 6, hvor forbindelsen er repræsenteret af den følgende strukturformel:
eller et farmaceutisk acceptabelt salt deraf, hvor Rio er uafhængigt valgt fra gruppen bestående af -halogen, -CN, -NO2, -OR5, -SR5, -NReR7, -S(0)iR5, -NRiiS( = 0)iRs, -S(0)iNRi2Ri3, -C( = 0)0Rs, -0C(=0)Rs, -C(=S)ORs, -OC(=S)Rs' ' C(=0)NRi2Ri3, -NRiiC( = 0)Rs, -C( = S)NRi2Ri3, -NRuC( = S)R5, -C(=0)Rs, -C(=S)R5' -Oc(=°)OR5/ -0(C=0)NRi2Ri3, -NRh(C=0)0Rs, -NRii(C=S)OR5, ' 0(C=S)NRi2Ri3, -NRii(C=0)NRi2Ri3, -NRh(C=S)NRi2Ri3, -C(=0)R5, -C(=S)Rs, (Ci-Ce)alkyl, (C2-Ce)alkynyl, (C3-Cs)cycloalkyl, (C4-Cs)cycloalkenyl, (C3-C9)heterocycloalkyl, (C2-Ce)alkenyl, halo(Ci-Ce)alkyl, (Ci-C3)alkylsulfonylaminoalkyl, hydroxy(Ci-C6)alkyl, cyano(Ci-Ce)alkyl, (Ci-C3)alkylcarbonylamino(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy, (Ci-C6)alkoxy(Ci-C3)alkyl, aryl og heteroaryl, hvor cycloalkyl, heterocycloalkyl, aryl og heteroaryl -grupperne i grupperne repræsenteret af Rio er hver eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra halogen, -CN, (Ci-C6)alkyl, halo(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C3)alkoxy(Ci-C6)alkyl; og s er 0, 1, 2 eller 3.
9. Forbindelsen ifølge et hvilket som helst af kravene 1, 4, 5 eller 6, hvor forbindelsen er repræsenteret af den følgende strukturformel:
eller et farmaceutisk acceptabelt salt deraf, hvor Rio er uafhængigt valgt fra gruppen bestående af halogen, -CN, -N02, -OR5, -SR5, -NR6R7, -S(0)iR5, -NRiiS(=0)iRs, -S(0)iNRi2Ri3, -C(=0)0R5, -0C(=0)Rs, -C(=S)ORs, -OC(=S)^5' " C(=0)NRi2Ri3, -NRuC(=0)R5, -C(=S)NRi2Ri3, -NRiiC(=S)R5, -C(=0)Rs, -C(=S)Rs, -0C(=0)0Rs, -0(C=0)NRi2Ri3, -NRh(C=0)0R5, -NRii(C=S)ORs, ' 0(C=S)NRi2Ri3, -NRii(C=0)NRi2Ri3, -NRii(C=S)NRi2Ri3, -C(=0)R5, -C(=S)Rs, (Ci-Ce)alkyl, (C2-C6)alkynyl, (C3-Ce)cycloalkyl, (C4-C8)cycloalkenyl, (C3-Cgjheterocycloalkyl, (C2-Ce)alkenyl, halo(Ci-Ce)alkyl, (Ci-C3)alkylsulfonylaminoalkyl, hydroxy(Ci-C6)alkyl, cyano(Ci-Ce)alkyl, (Ci-C3)alkylcarbonylamino(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy ,(Ci-C6)alkoxy(Ci-C3)alkyl, aryl og heteroaryl, hvor cycloalkyl, heterocycloalkyl, aryl og heteroaryl -grupperne i grupperne repræsenteret af Rio er hver eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra halogen, -CN, (Ci-C6)alkyl, halo(Ci-Ce)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy og (Ci-C3)alkoxy(Ci-C6)alkyl; og s er 0, 1, 2 eller 3.
10. Forbindelsen ifølge et hvilket som helst af kravene 8 eller 9, hvor Rio er uafhængigt valgt fra gruppen bestående af -F, -Cl, -Br, -CN, (Ci-Ce)alkyl, (Ci-Ce)alkoxy, halo(Ci-C6)alkyl og halo(Ci-Ce)alkoxy.
11. Forbindelsen ifølge krav 10, hvor Rio er uafhængigt valgt fra gruppen bestående af-F, -Cl, -Br, -CN, -Me, -Et, -OMe, -CF3, og -OCF3.
12. Forbindelsen ifølge et hvilket som helst af kravene 1-11, hvor Ri er -H og R14, når til stede, er -Me.
13. Forbindelsen ifølge et hvilket som helst af kravene 1,3, 4 og 7-12, hvor ring A er repræsenteret af den følgende strukturformel:
hvor: R19 og R2o er hver uafhængigt valgt fra -H, halogen, -CN, -ORs, -NR6R7, -S(0)iRs, -NRiiS(=0)iRs, -C(=0)0Rs, -C(=0)NRi2Ri3, -NRnC(=0)R5, -C(=S)NRi2Ri3, -C(=0)R5, (Ci-Ce)alkyl, (C2-Ce)alkenyl, aryl, aryl(Ci-Ce)alkyl, heteroaryl arid heteroaryl(Ci-C6)alkyl, hvor hver af aryl og heteroaryl -grupperne repræsenteret af R19 og R2o er eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra gruppen bestående af halogen, -CN, (Ci-Ce)alkyl, halo(Ci-C6)alkyl, (Ci-C3)alkoxy, halo(Ci- C3)alkoxy og (Ci-C3)alkoxy(Ci-C6)alkyl.
14. Forbindelsen ifølge krav 13, hvor: R20 er -H og R19 er -OH, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy eller (Ci-C3)alkoxy(Ci-C3)alkoxy.
15. Forbindelsen ifølge et hvilket som helst af kravene 1, 3, 4 eller 7-12, hvor ring A er repræsenteret af den følgende strukturformel:
hvor: Rg og Rh, for hver forekomst, er uafhængigt -H, -halogen, -CN, -ORs, -NR6R7, -S(0)iR5, -C(=0)0Rs, -C(=0)NRi2Ri3, -C(=0)Rs, (Ci-Ce)alkyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, (C3-C9)heterocycloalkyl, aryl, heteroaryl, hvor hver (C3-C8)cycloalkyl, (C3-C9)heterocycloalkyl, aryl og heteroaryl repræsenteret af Rg og Rh er eventuelt substitueret med 1 til 3 substituenter valgt fra gruppen bestående af -F, -Cl, -Br, -CN, (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (Ci-C3)alkoxy, halo(Ci-C3)alkoxy, og (Ci-C6)alkoxy(Ci-C3)alkyl; x er et heltal fra 1 til 4; og y er et heltal fra 1 til 6.
16. Forbindelsen ifølge krav 15, hvor Rg er -H og Rh er -H.
17. Forbindelsen ifølge et hvilket som helst af kravene 1, 3-6 eller 12-16, hvor: Ri er -H; R2 er -H, halogen, -CN, -ORs, -C(=0)NRi2Ri3, -C(=0)0Rs, -C(0)Rs, (Ci-C6)alkyl, (C2-Ce)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(Ci-C3)alkyl, (C4-C6)cycloalkenyl, phenyl, phenyl(Ci-C3)alkyl, heteroaryl, heteroaryl(Ci-C3)alkyl, (Cs-C6)heterocycloalkyl, eller (Cs-C6)heterocycloalky(Ci-C3)alkyl, hvor heteroaryl er valgt fra pyridyl, pyridazinyl, pyridinonyl, pyridazinonyl, thiazolyl, oxazolyl, oxadiazolyl, pyrazinyl, pyrimidyl, indolyl, quinolyl, quinoxalinyl, triazol og thiophenyl, heterocycloalkyl er valgt fra oxetanyl, tetrahydrofuran, tetrahydropyran, piperidin, pyrrolidinyl og pyrrolidinonyl, og hver af (Ci-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(Ci-C3)alkyl, (C4-C6)cycloalkenyl, phenyl, phenyl(Ci-C3)alkyl, heteroaryl, heteroaryl(Ci-C3)alkyl, (C5-C6)heterocycloalkyl og (C5-C6)heterocycloalky(Ci-C3)alkyl grupper repræsenteret af R2 er eventuelt substitueret med 1 til 5 substituenter uafhængigt valgt fra halogen, -CN, (Ci-C3)alkyl, halo(Ci-C3)alkyl, (C2-Ce)alkynyl, -NReR7, -S(0)iRs, -C(0)Rs, -OH, (C3-C6)cycloalkyl, (Ci-C3)alkoxy og halo(Ci-C3)alkoxy; og R14, når til stede, er -H, -ORs, -NReR7, (Ci-Ce)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(Ci-C3)alkyl, (C3-C5)heterocycloalkyl, (C3-C5)heterocycloalkyl(Ci-C3)alkyl, heteroaryl, phenyl, phenyl(Ci-C3)alkyl og heteroaryl(Ci-C3)alkyl, hvor heteroaryl er valgt fra pyridyl, pyridazinyl, pyridinonyl, pyridazinonyl, thiazolyl, oxazolyl, oxadiazolyl, pyrazinyl, pyrimidyl, indolyl, quinolyl, quinoxalinyl og thiophenyl og triazolyl, (C3-C5)heterocycloalkyl er valgt fra oxetanyl, tetrahydrofuran, tetrahydropyran, piperidinyl og pyrrolidinyl, og hver af (Ci-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(Ci-C3)alkyl, (C3-C5)heterocycloalkyl, (C3-C5)heterocycloalkyl(Ci-C3)alkyl, heteroaryl, phenyl, phenyl(Ci-C3)alkyl og heteroaryl(Ci-C3)alkyl -grupperne repræsenteret af R14 er eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra halogen, (Ci-C6)alkyl, halo(Ci-C6)alkyl, (Ci-C3)alkoxy, -NR6R7, -S(0)iR5, -NR11SO2R5, -OH, -COORs, -C(=0)R5, og -C(=0)NRi2Ri3.
18. Forbindelsen ifølge et hvilket som helst af kravene 1 eller 3-17, hvor: R5 er valgt fra gruppen bestående af -H, (Ci-C3)alkyl, halo(Ci-C3)alkyl, (Ci-C3)alkoxy(Ci-C3)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(Ci-C3)alkyl, phenyl og phenyl(Ci-C3)alkyl, hvor phenyl-gruppen i grupperne repræsenteret af Rs er eventuelt substitueret med 1 til 3 substituenter uafhængigt valgt fra -F, -Cl, -Br, -CN, =0, -NReR7, (Ci-C3)alkyl, halo(Ci-C3)alkyl og (Ci-C3)alkoxy(Ci-C3)alkyl; R6 er -H eller (Ci-C3)alkyl; R7 er -H, (Ci-C3)alkyl, halo(Ci-C3)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(Ci-C3)alkyl eller (Ci-C3)alkoxy(Ci-C3)alkyl; Ru er -H eller (Ci-C3)alkyl; R12 er -H eller (Ci-C3)alkyl; og R13 er -H, (Ci-C3)alkyl, halo(Ci-C3)alkyl, (C3-C6)cycloalkyl(Ci-C3)alkyl eller (Ci-C3)alkoxy(Ci-C3)alkyl, eller R12 og R13 sammen med nitrogenatomet til hvilket de er bundet danner en pyrrolidin- eller piperidin-ring.
19. Forbindelsen ifølge krav 1, hvor forbindelsen er repræsenteret afen hvilken som helst af de følgende strukturformler:
20. Farmaceutisk sammensætning omfattende en farmaceutisk acceptabel bærer eller fortynder og en forbindelse ifølge et hvilket som helst af kravene 1-19 eller et farmaceutisk acceptabelt salt deraf.
21. Forbindelse ifølge et hvilket som helst af kravene 1-19 eller et farmaceutisk acceptabelt salt deraf, til anvendelse i inhibering af BACE-aktivitet i et individ med behov for sådan behandling, hvor individet har en lidelse valgt fra neurodegenerative lidelser, lidelser kendetegnet ved kognitiv forringelse, kognitiv svækkelse, dementia og sygdomme kendetegnet ved produktion af β-amyloid-aflejringer eller neurofibrillære degenerationer, Alzheimers sygdom, Trisomi 21 (Downs syndrom), hereditær hjerneblødning med Amyloidose af Dutch-typen (HCHWA-D), senildemens, cerebral amyloid-angiopati, degenerativ demens, demens af blandet vaskulær og degenerativ oprindelse, demens associeret med Parkinsons sygdom, demens associeret med progressiv supranukleær lammelse, demens associeret med cortical basal degeneration, Lewy body-demens-type af Alzheimers sygdom og glaukom.
22. Forbindelse ifølge et hvilket som helst af kravene 1-19 eller et farmaceutisk acceptabelt salt deraf, til anvendelse i behandling af en BACE-medicineret lidelse i et individ, hvor lidelsen er valgt fra neurodegenerative lidelser, lidelser kendetegnet ved kognitiv forringelse, kognitiv svækkelse, dementia og sygdomme kendetegnet ved produktion af β-amyloid-aflejringer eller neurofibrillære degenerationer, Alzheimers sygdom, Trisomi 21 (Downs syndrom), hereditær hjerneblødning med Amyloidose af Dutch-typen (HCHWA-D), senildemens, cerebral amyloid-angiopati, degenerativ demens, demens af blandet vaskulær og degenerativ oprindelse, demens associeret med Parkinsons sygdom, demens associeret med progressive supranukleær lammelse, demens associeret med cortical basal degeneration, Lewy body-demens-type af Alzheimers sygdom og glaukom.
23. Forbindelsen til anvendelse ifølge krav 22, hvor lidelsen er valgt fra gruppen bestående af Alzheimers sygdom, kognitiv svækkelse, Downs syndrom, HCHWA-D, kognitiv forringelse, senildemens, cerebral amyloid-angiopati, degenerativ demens, andre neurodegenerative lidelser, og glaukom.
24. Forbindelsen til anvendelse ifølge krav 23, hvor lidelsen er Alzheimers sygdom.
25. Forbindelsen til anvendelse ifølge krav 23, hvor lidelsen er glaukom.
DK10708684.5T 2009-03-13 2010-03-12 Inhibitorer af beta-sekretase DK2406240T3 (da)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US21014609P 2009-03-13 2009-03-13
US30754210P 2010-02-24 2010-02-24
PCT/US2010/027173 WO2010105179A2 (en) 2009-03-13 2010-03-12 Inhibitors of beta-secretase

Publications (1)

Publication Number Publication Date
DK2406240T3 true DK2406240T3 (da) 2016-02-01

Family

ID=42664888

Family Applications (1)

Application Number Title Priority Date Filing Date
DK10708684.5T DK2406240T3 (da) 2009-03-13 2010-03-12 Inhibitorer af beta-sekretase

Country Status (28)

Country Link
US (3) US8633212B2 (da)
EP (2) EP2801570A1 (da)
JP (2) JP5731414B2 (da)
KR (2) KR20120001756A (da)
CN (1) CN102348698B (da)
AP (1) AP2866A (da)
AR (1) AR075854A1 (da)
AU (1) AU2010223937B2 (da)
BR (1) BRPI1009333B8 (da)
CA (1) CA2753730C (da)
CO (1) CO6450683A2 (da)
DK (1) DK2406240T3 (da)
EA (1) EA020875B1 (da)
EC (1) ECSP11011398A (da)
ES (1) ES2571057T3 (da)
GE (1) GEP20135964B (da)
IL (1) IL214226A (da)
MA (1) MA33240B1 (da)
MX (1) MX2011009571A (da)
NZ (1) NZ594230A (da)
PE (1) PE20120219A1 (da)
PT (1) PT2406240E (da)
SG (1) SG173466A1 (da)
TN (1) TN2011000400A1 (da)
TW (1) TWI464153B (da)
UY (1) UY32490A (da)
WO (1) WO2010105179A2 (da)
ZA (2) ZA201106002B (da)

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8450308B2 (en) * 2008-08-19 2013-05-28 Vitae Pharmaceuticals, Inc. Inhibitors of beta-secretase
CA2753730C (en) 2009-03-13 2020-12-22 Vitae Pharmaceuticals, Inc. Inhibitors of beta-secretase
UA108363C2 (uk) 2009-10-08 2015-04-27 Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування
CN102812005B (zh) 2010-02-24 2014-12-10 生命医药公司 β-分泌酶抑制剂
WO2012071279A1 (en) 2010-11-23 2012-05-31 Amgen Inc. Spiro-amino-imidazolone and spiro-amino-dihydro-pyrimidinone compounds as beta-secretase modulators and methods of use
US8415483B2 (en) 2010-12-22 2013-04-09 Astrazeneca Ab Compounds and their use as BACE inhibitors
GB201100181D0 (en) 2011-01-06 2011-02-23 Eisai Ltd Fused aminodihydrothiazine derivatives
GB201101139D0 (en) 2011-01-21 2011-03-09 Eisai Ltd Fused aminodihydrothiazine derivatives
GB201101140D0 (en) 2011-01-21 2011-03-09 Eisai Ltd Fused aminodihydrothiazine derivatives
WO2012109165A1 (en) 2011-02-07 2012-08-16 Amgen Inc. 5-amino-oxazepine and 5-amino-thiazepane compounds as beta-secretase antagonists and methods of use
EP2675810A1 (en) 2011-02-15 2013-12-25 Amgen Inc. Spiro-amino-imidazo-fused heterocyclic compounds as beta-secretase modulators and methods of use
WO2013044092A1 (en) 2011-09-21 2013-03-28 Amgen Inc. Amino-oxazines and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use
WO2013054108A1 (en) 2011-10-10 2013-04-18 Astrazeneca Ab Mono-fluoro beta-secretase inhibitors
TWI557112B (zh) * 2012-03-05 2016-11-11 百靈佳殷格翰國際股份有限公司 β－分泌酶抑制劑
WO2013169531A1 (en) 2012-05-09 2013-11-14 Boehringer Ingelheim International Gmbh Methods for making oxetan-3-ylmethanamines
MX2014014066A (es) * 2012-05-30 2015-03-19 Comentis Inc Compuestos de cromano.
EP2669286A1 (en) * 2012-05-31 2013-12-04 Ares Trading S.A. Spiro tetrahydro-benzothiophen derivatives useful for the treatment of neurodegenerative diseases
US9000184B2 (en) 2012-06-20 2015-04-07 Astrazeneca Ab Cyclohexane-1,2′-naphthalene-1′,2″-imidazol compounds and their use as BACE inhibitors
US9000182B2 (en) 2012-06-20 2015-04-07 Astrazeneca Ab 2H-imidazol-4-amine compounds and their use as BACE inhibitors
US9000183B2 (en) 2012-06-20 2015-04-07 Astrazeneca Ab Cyclohexane-1,2′-indene-1′,2″-imidazol compounds and their use as BACE inhibitors
US9000185B2 (en) * 2012-06-20 2015-04-07 Astrazeneca Ab Cycloalkyl ether compounds and their use as BACE inhibitors
US10548882B2 (en) * 2012-06-21 2020-02-04 Astrazeneca Ab Camsylate salt
TW201422592A (zh) * 2012-08-27 2014-06-16 Boehringer Ingelheim Int β－分泌酶抑制劑
WO2014051653A1 (en) 2012-09-27 2014-04-03 Portola Pharmaceuticals, Inc. Bicyclic dihydropyridone kinase inhibitors
JP2015532282A (ja) 2012-09-28 2015-11-09 ヴァイティー ファーマシューティカルズ，インコーポレイテッド β−セクレターゼの阻害剤
US9725469B2 (en) 2012-11-15 2017-08-08 Amgen, Inc. Amino-oxazine and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use
EP2922835B1 (en) 2012-11-21 2017-08-09 Boehringer Ingelheim International GmbH Process for making n-sulfinyl alpha-amino amides
US10550327B2 (en) 2012-11-21 2020-02-04 Merck Patent Gmbh Polymerisable compounds and the use thereof in liquid-crystal displays
ES2655788T5 (es) 2013-01-28 2024-05-22 Moelnlycke Health Care Ab Dispositivo de aspiración
WO2014160775A1 (en) 2013-03-26 2014-10-02 Saint Louis University Compositions and methods for the treatment of malaria
US10053453B2 (en) 2014-10-07 2018-08-21 Astrazeneca Ab Compounds and their use as BACE inhibitors
JP6319805B2 (ja) * 2014-10-08 2018-05-09 田岡化学工業株式会社 スピロビフルオレン骨格を有するジオール化合物およびその製造方法
CN106083764B (zh) * 2016-07-11 2018-09-18 上海皓元生物医药科技有限公司 一种用于制备axl抑制剂的高纯度中间体的手性拆分方法
CN110650735A (zh) * 2017-05-16 2020-01-03 芝加哥大学 通过钯-催化的分子内链烯基化的4,5-螺环的高度非对映选择性结构
TWI717057B (zh) * 2017-06-14 2021-01-21 日商日本曹達股份有限公司 二唑啉化合物及有害生物防除劑
KR101969528B1 (ko) 2017-09-29 2019-04-16 에스케이텔레콤 주식회사 터치 디스플레이를 제어하는 장치와 방법 및 터치 디스플레이 시스템
WO2019168874A1 (en) 2018-02-27 2019-09-06 The Research Foundation For The State University Of New York Difluoromethoxylation and trifluoromethoxylation compositions and methods for synthesizing same
CN108675923B (zh) * 2018-06-27 2021-04-27 沅江华龙催化科技有限公司 一种由环酮化合物与2-芳基丙烯及二甲亚砜共同构建螺环化合物的方法
CN108675922B (zh) * 2018-06-27 2021-04-27 沅江华龙催化科技有限公司 一种螺环化合物及其合成方法
JPWO2021065898A1 (da) 2019-09-30 2021-04-08

Family Cites Families (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5745185A (en) * 1980-07-21 1982-03-13 Eisai Co Ltd Hydantoin derivative and its preparation
CA2113818A1 (en) * 1991-08-28 1993-03-18 Robert C. Gadwood Spirocyclic benzopyran imidazolines
CA2189634A1 (en) 1994-05-06 1995-11-16 John J. Baldwin Combinatorial dihydrobenzopyran library
US7700603B2 (en) 2003-12-15 2010-04-20 Schering Corporation Heterocyclic aspartyl protease inhibitors
US7763609B2 (en) * 2003-12-15 2010-07-27 Schering Corporation Heterocyclic aspartyl protease inhibitors
JP5020638B2 (ja) 2003-12-15 2012-09-05 シェーリング コーポレイション 複素環式アスパルチルプロテアーゼインヒビター
US7592348B2 (en) * 2003-12-15 2009-09-22 Schering Corporation Heterocyclic aspartyl protease inhibitors
AU2005264915A1 (en) * 2004-06-16 2006-01-26 Wyeth Amino-5,5-diphenylimidazolone derivatives for the inhibition of beta-secretase
AU2005264917A1 (en) 2004-06-16 2006-01-26 Wyeth Diphenylimidazopyrimidine and -imidazole amines as inhibitors of B-secretase
EP1804794B1 (en) 2004-10-13 2013-07-31 Merck Sharp & Dohme Corp. Spiropiperidine compounds useful as beta-secretase inhibitors for the treatment of alzhermer s disease
EP1891021B1 (en) 2005-06-14 2019-01-23 Merck Sharp & Dohme Corp. Aspartyl protease inhibitors
US7759354B2 (en) 2005-06-14 2010-07-20 Schering Corporation Bicyclic guanidine derivatives as asparyl protease inhibitors, compositions, and uses thereof
TW200738683A (en) 2005-06-30 2007-10-16 Wyeth Corp Amino-5-(5-membered)heteroarylimidazolone compounds and the use thereof for β-secretase modulation
WO2007005404A1 (en) 2005-06-30 2007-01-11 Wyeth AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR ß-SECRETASE MODULATION
TW200730523A (en) 2005-07-29 2007-08-16 Wyeth Corp Cycloalkyl amino-hydantoin compounds and use thereof for β-secretase modulation
BRPI0614576B1 (pt) 2005-07-29 2017-05-30 Koninklijke Philips Nv dispositivo de passar a ferro a vapor
KR20080050430A (ko) 2005-09-26 2008-06-05 와이어쓰 베타-세크레타제 (ｂａｃｅ) 억제제로서아미노-5-[4-(디플루오로메톡시)페닐]-5-페닐이미다졸론화합물
BRPI0617852A2 (pt) 2005-10-25 2011-08-09 Shionogi & Co compostos derivados de aminodi-hidrotiazina assim como composições contendo os mesmos
US7872009B2 (en) * 2005-11-21 2011-01-18 Amgen Inc. Beta-Secretase modulators and methods of use
DE102005057688A1 (de) 2005-12-01 2007-06-14 Endress + Hauser Flowtec Ag Vorrichtung zur Bestimmung und/oder Überwachung des Massedurchflusses eines gasförmigen Mediums
BRPI0620025A2 (pt) 2005-12-19 2011-10-25 Wyeth Corp composto, método para o tratamento de uma doença ou transtorno associado a atividade excessiva de bace, método para modular a atividade de bace, composição farmacêutica e uso do composto
EP1974278A4 (en) 2005-12-20 2012-01-04 Fieldbus Foundation SYSTEM AND METHOD FOR IMPLEMENTING INSTRUMENTED SAFETY SYSTEMS
WO2007100536A1 (en) 2006-02-24 2007-09-07 Wyeth DIHYDROSPIRO[DIBENZO[A,D][7]ANNULENE-5,4'-IMIDAZOL] COMPOUNDS FOR THE INHIBITION OF β-SECRETASE
AR061264A1 (es) 2006-06-12 2008-08-13 Schering Corp Inhibidores de aspartil-proteasas derivados de pirimidina, composiciones farmaceuticas que los contienen y usos para tratar enfermedades cognitivas o neurodegenerativas, y como inhibidores del virus vih.
SI2042480T1 (sl) * 2006-07-18 2013-08-30 Astellas Pharma Inc. Aminoindanski derivati ali njegova sol
JP2010502705A (ja) 2006-09-07 2010-01-28 メルク エンド カムパニー インコーポレーテッド アルツハイマー病の治療用としてのスピロピペリジンベータセクレターゼ阻害剤
TW200831484A (en) 2006-12-20 2008-08-01 Astrazeneca Ab New compounds
TW200831091A (en) 2006-12-20 2008-08-01 Astrazeneca Ab New compounds
WO2008076044A1 (en) 2006-12-20 2008-06-26 Astrazeneca Ab Novel 2-amino-5, 5-diaryl-imidazol-4-ones
CL2008000784A1 (es) 2007-03-20 2008-05-30 Wyeth Corp Compuestos amino-5-[-4-(diflourometoxi) fenil sustituido]-5-fenilmidazolona, inhibidores de b-secretasa; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar alzheimer, deterioro cognitivo, sindrome de down, disminucion co
AR065814A1 (es) 2007-03-23 2009-07-01 Wyeth Corp Derivados de 5-fenilimidazolona,inhibidores de beta-secretasa,composiciones farmaceuticas que los contienen y usos para prevenir y/o tratar trastornos asociados a niveles beta-amiloides elevados.
AU2008245082B8 (en) 2007-04-24 2012-09-13 Shionogi & Co., Ltd. Aminodihydrothiazine derivatives substituted with a cyclic group
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
TW200902503A (en) 2007-05-15 2009-01-16 Astrazeneca Ab New compounds
BRPI0907563A2 (pt) 2008-02-18 2015-08-04 Hoffmann La Roche Derivados de 4,5-di-hidro-xazol-2-il amina
TWI431004B (zh) 2008-05-02 2014-03-21 Lilly Co Eli Ｂａｃｅ抑制劑
WO2010013302A1 (ja) 2008-07-28 2010-02-04 エーザイ・アール・アンド・ディー・マネジメント株式会社 スピロアミノジヒドロチアジン誘導体
AU2009277485B2 (en) 2008-07-28 2013-05-02 Eisai R&D Management Co., Ltd. Spiroaminodihydrothiazine derivatives
US8450308B2 (en) 2008-08-19 2013-05-28 Vitae Pharmaceuticals, Inc. Inhibitors of beta-secretase
PE20110805A1 (es) 2008-09-11 2011-11-09 Amgen Inc Compuestos con anillos espiro-triciclicos como moduladores de beta-secretasas y metodos de uso
MX2011005346A (es) 2008-11-23 2011-06-16 Pfizer Lactamas como inhibidores de beta secretasa.
CA2753730C (en) 2009-03-13 2020-12-22 Vitae Pharmaceuticals, Inc. Inhibitors of beta-secretase
WO2011072064A1 (en) 2009-12-08 2011-06-16 Array Biopharma Inc. S piro [chroman - 4, 4 ' - imidazol] ones as beta - secretase inhibitors
CN102812005B (zh) 2010-02-24 2014-12-10 生命医药公司 β-分泌酶抑制剂
TWI557112B (zh) 2012-03-05 2016-11-11 百靈佳殷格翰國際股份有限公司 β－分泌酶抑制劑
TW201422592A (zh) 2012-08-27 2014-06-16 Boehringer Ingelheim Int β－分泌酶抑制劑
JP2015532282A (ja) * 2012-09-28 2015-11-09 ヴァイティー ファーマシューティカルズ，インコーポレイテッド β−セクレターゼの阻害剤

Also Published As

Publication number Publication date
TN2011000400A1 (en) 2013-03-27
GEP20135964B (en) 2013-11-11
MX2011009571A (es) 2011-10-19
US8633212B2 (en) 2014-01-21
EP2406240B1 (en) 2015-12-23
MA33240B1 (fr) 2012-05-02
IL214226A (en) 2015-06-30
EP2801570A1 (en) 2014-11-12
CA2753730C (en) 2020-12-22
KR20170127048A (ko) 2017-11-20
AU2010223937A1 (en) 2011-08-11
BRPI1009333B8 (pt) 2021-05-25
PT2406240E (pt) 2016-02-24
EA201101026A1 (ru) 2012-03-30
JP5731414B2 (ja) 2015-06-10
IL214226A0 (en) 2011-09-27
KR101908255B1 (ko) 2018-10-15
BRPI1009333B1 (pt) 2020-10-13
PE20120219A1 (es) 2012-03-19
ES2571057T3 (es) 2016-05-23
US20140200223A1 (en) 2014-07-17
AP2866A (en) 2014-03-31
ZA201700326B (en) 2018-04-25
NZ594230A (en) 2013-11-29
EA020875B1 (ru) 2015-02-27
AU2010223937B2 (en) 2015-01-22
US9212153B2 (en) 2015-12-15
US20110071126A1 (en) 2011-03-24
KR20120001756A (ko) 2012-01-04
WO2010105179A2 (en) 2010-09-16
SG173466A1 (en) 2011-09-29
ZA201106002B (en) 2017-11-29
AR075854A1 (es) 2011-05-04
BRPI1009333A2 (pt) 2017-02-14
AP2011005913A0 (en) 2011-10-31
US10336717B2 (en) 2019-07-02
CA2753730A1 (en) 2010-09-10
ECSP11011398A (es) 2011-11-30
CN102348698A (zh) 2012-02-08
TWI464153B (zh) 2014-12-11
CN102348698B (zh) 2015-06-03
WO2010105179A3 (en) 2010-11-11
CO6450683A2 (es) 2012-05-31
TW201041858A (en) 2010-12-01
EP2406240A2 (en) 2012-01-18
JP2012520324A (ja) 2012-09-06
UY32490A (es) 2010-10-29
JP2015147792A (ja) 2015-08-20
US20160272600A1 (en) 2016-09-22

Similar Documents

Publication Publication Date Title
DK2406240T3 (da) Inhibitorer af beta-sekretase
US20110294776A1 (en) Pyrrolo[2,1-F] [1,2,4] Triazin-4-Ylamines IGF-1R Kinase Inhibitors for the Treatment of Cancer and Other Hyperproliferative Diseases
AU2008343524B2 (en) 6H-dibenzo [B, E] oxepine derived nonsteroidal mineralocorticoid receptor antagonists
TW201020256A (en) Inhibitors of beta-secretase
JP2004509894A (ja) 置換アゼピノ［４，５−ｂ］インドリン誘導体
EP2539322A1 (en) Inhibitors of beta-secretase
EP1891057B1 (en) Azabicyclo[3.1.0]hexane derivaives as dopamin d3 receptor modulators
WO2007022933A1 (en) Triazole derivatives as modulators of dopamine d3 receptors
JP2020500841A (ja) イミダゾピラジノンの投与を含む併用療法
KR20150119926A (ko) 비시클로 2,3-벤조디아제핀 및 스피로시클릭 치환된 2,3-벤조디아제핀
KR20120048618A (ko) 신규한 아릴피페라진-함유 이미다졸 4-카복사마이드 유도체 및 이를 포함하는 약학 조성물
CN114805311A (zh) 螺环茚
AU2016338992B2 (en) Dopamine D3 receptor antagonists having a morpholine moiety
EP2010523A1 (en) Spirocompounds useful as modulators for dopamine d3 receptors
CN113754635B (zh) 稠环类化合物及其制备方法和用途
CN113527307A (zh) 含三唑基的并环类衍生物抑制剂、其制备方法和应用