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AR076126A1 - Compuestos biciclicos como inhibidores de diacilglicerol aciltransferasa - Google Patents

Compuestos biciclicos como inhibidores de diacilglicerol aciltransferasa

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Publication number
AR076126A1
AR076126A1 ARP100100824A ARP100100824A AR076126A1 AR 076126 A1 AR076126 A1 AR 076126A1 AR P100100824 A ARP100100824 A AR P100100824A AR P100100824 A ARP100100824 A AR P100100824A AR 076126 A1 AR076126 A1 AR 076126A1
Authority
AR
Argentina
Prior art keywords
alkyl
carbonyl
cycloalkyl
sulfonyl
amino
Prior art date
Application number
ARP100100824A
Other languages
English (en)
Original Assignee
Schering Corp
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 Schering Corp filed Critical Schering Corp
Publication of AR076126A1 publication Critical patent/AR076126A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/50—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
    • C07D239/84—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
    • C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
    • 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
    • C07D403/06—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
    • 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
    • C07D403/12—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 chain containing hetero atoms as chain links
    • 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
    • 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
    • C07D498/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Indole Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

Composiciones farmacéuticas que comprenden los compuestos heterocíclicos y el uso de los compuestos para tratar o prevenir una enfermedad cardiovascular, un trastorno metabolico, obesidad o un trastorno relacionado con la obesidad, diabetes, dislipidemia, una complicacion diabética, trastorno de tolerancia a la glucosa o glucosa perjudicada en ayunas. Reivindicacion 1: Un compuesto, o una sal aceptable desde el punto de vista farmacéutico de dicho compuesto, o una sal, solvato, o éster aceptables desde el punto de vista farmacéutico de dicha prodroga, estando el compuesto representado por la Formula (1): o un estereoisomero o tautomero de dicho compuesto, en el cual el enlace denotado por --- representa un enlace simple o un enlace doble; W se selecciona del grupo que consiste en C(R4), C(R4R4), N, N(R4), S u O; X se selecciona del grupo que consiste en C(R4), C(R4R4), N, N(R4), S u O; Y se selecciona del grupo que consiste en C(R4), C(R4R4), N, N(R4), S u O; R4 está presente dependiendo de la valencia permitida y se selecciona de H, alquilo, R1, -OH, (=O), o hidroxialquilo; W, X o Y está sustituido con R1 dependiendo de la valencia permitida; R1 se selecciona del grupo que consiste en alquilo-, arilo-, arilalquilo-, heteroarilo-, heteroarilalquilo-, cicloalquilo-, (cicloalquil)alquilo-, heterocicloalquilo-, (heterocicloalquil)alquilo-, (alquil)amino-, (aril)amino-, (arilalquil)amino-, (heteroaril)amino-, (heteroarilalquil)amino-, (cicloalquil)amino-, ((cicloalquil)alquil)amino-, (heterocicloalquil)amino-, ((heterocicioalquil)alquil)amino-, (alquil)carbonilo-, (cicloalquil)carbonilo-, (cicloalquil)alquilcarbonilo-, (heterocicloalquil)carbonilo-, (heterociclil)alquilcarbonilo-, (aril)carbonilo-, (aril)alquilcarbonilo-, (heteroaril)carbonilo-, (heteroaril)alquilcarbonilo-, (alquil)tiocarbonilo-, (cicloalquil)tiocarbonilo-, (cicloalquil)alquiltiocarbonilo-, (heterocicloalquil)tiocarbonilo-, (heterociclil)alquiltiocarbonilo-, (aril)tiocarbonilo-, (aril)alquiltiocarbonilo-, (heteroaril)tiocarbonilo-, (heteroaril)alquiltiocarbonilo-, (alquiloxi)carbonilo-, (cicloalquiloxi)carbonilo-, (heterocicloalquiloxi)carbonilo-, (ariloxi)carbonilo-, (arilalquiloxi)carbonilo-, (heteroariloxi)carbonilo-, (heteroarilalquiloxi)carbonilo-, (alquilamino)carbonilo-, (cicloalquilamino)carbonilo-, (heterocicloalquilamino)carbonilo-, (arilamino)carbonilo-, (arilalquilamino)carbonilo-, (heteroarilamino)carbonil[, (heteroarilalquilamino)carbonilo-, (alquil)sulfonilo-, (cicloalquil)sulfonilo-, (heterocicloalquil)sulfonilo-, (aril)sulfonilo-, (arilalquil)sulfonilo-, (heteroaril)sulfonilo-, (heteroarilalquil)sulfonilo-, (alquilamino)sulfonilo-, (cicloalquilamino)sulfonilo-, (heterocicloalquilamino)sulfonilo-, (arilamino)sulfonilo-, (arilalquilamino)sulfonilo-, (heteroarilamino)sulfonilo- y (heteroarilalquilamino)sulfonilo-, donde cada uno de estos grupos R1 no está sustituido o sustituido en forma independiente y opcional con 1-4 sustituyentes seleccionados de manera independiente de halogeno, amino, alquilamino, hidroxi, alcoxi, alquilo, cicloalquilo, carboxi, carboxiéster, metilendioxi, CN, cianoalquilo-, nitro y CF3; A se selecciona del grupo que consiste en C(R5) o N; B se selecciona del grupo que consiste en C(R5) o N; C se selecciona del grupo que consiste en C(R5) o N; D se selecciona del grupo que consiste en C(R5) o N; R5 se selecciona de H, alquilo, cicloalquilo, amino, alquilamino, hidroxi, alcoxi, halogeno, cicloalquilo, heterocicloalquilo, heteroarilo o arilo, donde cada uno de estos grupos R5 no está sustituido o sustituido en forma independiente y opcional con 1-4 sustituyentes seleccionados de manera independiente de halogeno, amino, alquilamino, hidroxi, alcoxi, alquilo, cicloalquilo, CN y CF3; cada uno de A, B, C o D está sustituido en forma opcional, dependiendo de la valencia permitida, con cicloalquilo, heterocicloalquilo, heteroarilo o arilo, donde cada uno de estos grupos no está sustituido o sustituido en forma independiente y opcional con 1-4 sustituyentes seleccionados de manera independiente de halogeno, amino, alquilamino, hidroxi, alcoxi, alquilo, cicloalquilo, CN y CF3; R2 es heteroarilo, en donde dicho heteroarilo no está sustituido o sustituido en forma independiente y opcional con 1-4 sustituyentes seleccionados de manera independiente de halogeno, amino, alquilamino, hidroxi, alcoxi, alquilo, cicloalquilo, CN y CF3; Z se selecciona del grupo que consiste en un enlace, O, N(R6), alquilo, carbonilo y sulfonilo; R6 se selecciona de H o alquilo; R3 se selecciona del grupo que consiste en cicloalquilo, heterociclilo, arilo y heteroarilo, donde cada uno de estos grupos R3 no está sustituido o sustituido en forma independiente y opcional con 1-4 sustituyentes seleccionados de manera independiente de halogeno, amino, alquilamino, hidroxi, alcoxi, alquilo, cicloalquilo, -CN, -CF3, -C(O)NH(R6), -CON(R6)2, -COOH, -C(O)-Oalquilo, -alquilCOOH, -alquil-C(O)O-alquilo, -alquil-C(O)NH2, -alquil-C(O)-NH-(CH2)1-3-CN, -alquil-C(O)-NH-(CH2)1-3-(heteroarilo), bioisoéster -COOH o bioisoéster -alquilCOOH.
ARP100100824A 2009-03-18 2010-03-16 Compuestos biciclicos como inhibidores de diacilglicerol aciltransferasa AR076126A1 (es)

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US16121209P 2009-03-18 2009-03-18

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ARP100100824A AR076126A1 (es) 2009-03-18 2010-03-16 Compuestos biciclicos como inhibidores de diacilglicerol aciltransferasa
ARP100100823A AR075858A1 (es) 2009-03-18 2010-03-16 Compuestos biciclicos como inhibidores de diacilglicerol aciltransferasa

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US (2) US20120022057A1 (es)
EP (2) EP2408744A1 (es)
JP (2) JP2012520886A (es)
AR (2) AR076126A1 (es)
AU (2) AU2010226829A1 (es)
CA (2) CA2755251A1 (es)
TW (2) TW201043607A (es)
WO (2) WO2010107765A1 (es)

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