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AR059802A1 - Compuestos y derivados de dibencilamina, combinaciones y composiciones farmaceuticas que los comprenden y el uso de estos derivados en el tratamiento de enfermedades mediadas por la actividad de cetp. - Google Patents

Compuestos y derivados de dibencilamina, combinaciones y composiciones farmaceuticas que los comprenden y el uso de estos derivados en el tratamiento de enfermedades mediadas por la actividad de cetp.

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Publication number
AR059802A1
AR059802A1 ARP070100979A ARP070100979A AR059802A1 AR 059802 A1 AR059802 A1 AR 059802A1 AR P070100979 A ARP070100979 A AR P070100979A AR P070100979 A ARP070100979 A AR P070100979A AR 059802 A1 AR059802 A1 AR 059802A1
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AR
Argentina
Prior art keywords
alkyl
groups
halo
cyano
optionally substituted
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ARP070100979A
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English (en)
Inventor
Ravi Shanker Garigipati
Bruce Allen Lefker
David Austen Perry
George Chang
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Pfizer Prod Inc
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Publication of AR059802A1 publication Critical patent/AR059802A1/es

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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • C07D257/06—Five-membered rings with nitrogen atoms directly attached to the ring carbon atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07D401/12—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 chain containing hetero atoms as chain links
    • 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
    • C07D401/14—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 three or more hetero rings
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    • 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
    • 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
    • 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
    • C07D413/12—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 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • C07D487/04—Ortho-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
    • C07D491/04—Ortho-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
    • C07D513/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Vascular Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Compuestos de dibencilamina y derivados, composiciones farmacéuticas que contienen estos compuestos y el uso de estos compuestos para elevar los niveles plasmáticos de ciertos Iípidos, incluyendo el colesterol asociado a lipoproteínas de alta densidad y para reducir los niveles plasmáticos de otros lípidos, tales como el colesterol LDL y los triglicéridos y, por consiguiente, para tratar enfermedades que se exacerban por bajos niveles de colesterol-HDL y/o altos niveles de colesterol-LDL y triglicéridos, tales como aterosclerosis y enfermedades cardiovasculares en algunos mamíferos, incluyendo seres humanos. Reivindicacion 1: Un compuesto de formula (1) o una sal farmacéuticamente aceptable de dicho compuesto; donde A es - COOalquilo C1-4, ciano, -CHO, -CONH2, -COalquilo C1-4 o Q, donde Q es un anillo de cinco o seis miembros, totalmente saturado, parcialmente insaturado o totalmente insaturado, donde cada átomo del anillo, excepto para el átomo conectado al N de la formula 1, puede reemplazarse por un átomo de nitrogeno, oxigeno o azufre, y donde cada átomo del anillo puede estar opcionalmente sustituido con ciano, una cadena lineal o ramificada, totalmente saturada, parcialmente insaturada o tota mente insaturada, que tiene de 1 a 6 átomos de carbono, o un anillo totalmente saturado, parcialmente insaturado o totalmente insaturado, que tiene de 3 a 8 átomos de carbono, donde cada átomo de carbono de dicha cadena o de dicho anillo se reemplaza opcionalmente por un heteroátomo seleccionado entre nitrogeno, oxigeno y azufre, y dicho átomo de carbono de dicha cadena o de dicho anillo está opcionalmente mono-, di- o trisustituido con amino, halo, ciano, hidroxi, oxo, carboxilo, alcoxicarbonilo C1-6, (alquilo C1-6 opcionalmente sustituido con uno a nueve grupos halo o uno o dos grupos hidroxilo, (alcoxi C1-6 opcionalmente sustituido con uno a nueve grupos halo o uno o dos grupos hidroxilo) o (alquiltio C1-6 opcionalmente sustituido con uno a nueve grupos halo o uno o dos grupos hidroxilo), y dicho átomo de nitrogeno de dicha cadena o de dicho anillo está opcionalmente mono- o disustituido con ciano, oxo, alcoxicarbonilo C1-6 o (alquilo C1-6 opcionalmente sustituido con uno a nueve grupos halo o uno o dos grupos hidroxilo), dicho átomo de azufre de dicha cadena o de dicho anillo está sustituido con uno o dos grupos oxo, uno a cinco grupos fluor o amino, y dicha cadena o dicho anillo está opcionalmente mono- di- o trisustituido con un grupo V, donde V es un anillo de tres a seis miembros, totalmente saturado, parcialmente saturado o totalmente insaturado, que contiene de cero a cuatro heteroátomos seleccionados entre nitrogeno, oxigeno o azufre y opcionalmente sustituido con uno a cinco grupos seleccionados entre hidrogeno, halo, ciano, hidroxi, oxo, carboxilo, alcoxicarbonilo C1-6, (alquilo C1-6 opcionalmente sustituido con uno a nueve grupos halo o uno o dos grupos hidroxilo), (alcoxi C1-6 opcionalmente sustituido con uno a nueve grupos halo o uno o dos grupos hidroxilo) o (alquiltio C1-6 opcionalmente sustituido con uno a nueve grupos halo o uno o dos grupos hidroxilo); B es -NR15R16 o un heterociclo de 3 a 8 miembros que tiene 1 o 2 heteroátomos seleccionados entre oxigeno, nitrogeno y azufre, donde dicho heterociclo está unido a Y en un heteroátomo y donde dicho heterociclo está opcionalmente mono- o di-sustituido con R20, X es C o N, donde si X es N, R4 está ausente; Y es - CR11R12, cada uno de R1, R2, R3, R4, R5, R6 y R7 es independientemente hidrogeno, halo, ciano, hidroxi, nitro, (alquilo C1-6 opcionalmente sustituido con uno a nueve grupos halo, uno o dos grupos hidroxilo, uno o dos alcoxi C1-6, uno o dos grupos amino, uno o dos grupos nitro, ciano, oxo o carboxi), (alcoxi C1-6 opcionalmente sustituido con uno a nueve grupos halo, uno o dos grupos hidroxilo o ciano) o (alquiltio C1-6 opcionalmente sustituido con uno a nueve grupos halo, uno o dos grupos hidroxilo o ciano), o R1 y R2 o R2 y R3 se toman juntos para formar un anillo de 5 a 7 miembros, parcialmente insaturado o totalmente insaturado, donde cada átomo de carbono de dicho anillo se reemplaza opcionalmente por un átomo de oxigeno, donde los átomos de oxigeno no están conectados entre si, donde dicho anillo está opcionalmente mono-, di-, tri- o tetra-sustituido con halo, y opcionalmente mono- o di-sustituido con hidroxi, amino, nitro, ciano, oxo, carboxi, (alquilo C1-6 opcionalmente sustituido con uno a nueve grupos halo, uno o dos grupos hidroxilo, uno o dos grupos alcoxi C1-6, uno o dos grupos amino, uno o dos grupos nitro, ciano, oxo o carboxi) o (alcoxi C1-6 opcionalmente sustituido con uno a nueve grupos halo, uno o dos grupos hidroxilo o ciano); cada R8, R9, R10, R13 y R14 es independientemente hidrogeno, arilo o alquilo C1-6 opcionalmente sustituido con uno a nueve grupos halo; R11 es hidrogeno, arilo, (cicloalquilo C3-6 opcionalmente sustituido con arilo, uno a tres grupos alquilo C1-6, uno a tres grupos alcoxi C1-6, uno a tres grupos haloalquilo C1-6, uno a tres grupos haloalcoxi C1-6, uno o dos grupos hidroxilo o uno a nueve grupos halo) o (alquilo C1-6 donde dicho grupo alquilo C1-6 está opcionalmente sustituido con arilo, uno a tres grupos alcoxi C1-6, uno a tres grupos haloalquilo C1-6, uno a tres grupos haloalcoxi C1-6, uno o dos grupos hidroxilo o uno a nueve grupos halo); R12 es hidrogeno; cada uno de R15 y R16 es independientemente hidrogeno, -alquil C1-6-NR8R9, -alquil C0-6-CO-NR8R9, -alquil C0-6-CO-OR10, -alquil C1-6-NR13-alquil C0-6-CO-O-R10, -alquil C1-6-NR13-alquil C0-6-CO-R14, -alquil C1-6-NR13-alquil C0-6-SO2R10, -alquil C1-6-O-CO-NR8R9, -alquenil C2-6-CO-O-R10, -alquil C0-6-arilo, -alquil C0-6-heteroarilo, -alquil C1-6-O-arilo, -alquil C1-6-O-heteroarilo, -alquil C0-6-heterociclo, -alquil C0-6-cicloalquilo C3-6, -alquil C0-6-cicloalquenilo C3-6, alquinilo C2-6, alquenilo C2-6, alquilo C1-6, ciano o -CO-alquilo C1- 6, donde cada uno de dichos sustituyentes arilo, heteroarilo, heterociclo, cicloalquenilo, cicloalquilo, alquinilo, alquenilo y alquilo está opcionalmente sustituido independientemente con uno a nueve grupos halo, uno o dos grupos hidroxi, uno a tres grupos alquilo C1-6, uno a tres grupos haloalquilo C1-6, uno a tres grupos alcoxi C1-6, uno a tres grupos haloalcoxi C1-6, uno o dos grupos amino, uno o dos grupos nitro, ciano, oxo o carboxi; y cada R20 es independientemente -alquil C0-6- NR8R9, -alquil C0-6-CO-NR8R9, -alquil C0-6-CO-OR10, -alquil C0-6-NR13-alquil C0-6-CO-O-R10, -alquil C0-6-NR13-alquil C0-6-CO-R14, -alquil C0-6-NR13-alquil C0-6-SO2R10, -alquil C0-6-O-CO-NR8R9, -O-alquil C1-6-CO-OR10, halo, -alquenil C2-6-CO-O-R10, - alquil C0-6-arilo, -alquil C0-6-heteroarilo, -alquil C0-6-O-arilo, -alquil C0-6-O-heteroarilo, -alquil C0-6-heterociclo, -alquil C0-6-cicloalquilo C3-6, - alquil C0-6-cicloalquenilo C3-6, alquinilo C2-6, alquenilo C2-6, alquilo C1-6, alcoxi C1-6, oxo, ciano o -CO-alquilo C1-6, donde cada uno de dichos sustituyentes arilo, heteroarilo, heterociclo, cicloalquenilo, cicloalquilo, alquinilo, alquenilo y alquilo está opcionalmente sustituido independientemente con uno a nueve grupos halo, uno o dos grupos hidroxi, uno o dos grupos alquilo C1-6, uno o dos grupos haloalquilo C1-6, uno o dos alcoxi C1-6, uno o dos grupos haloalcoxi C1-6, uno o dos grupos amino, uno o dos grupos nitro, ciano, oxo o carboxi.
ARP070100979A 2006-03-10 2007-03-09 Compuestos y derivados de dibencilamina, combinaciones y composiciones farmaceuticas que los comprenden y el uso de estos derivados en el tratamiento de enfermedades mediadas por la actividad de cetp. AR059802A1 (es)

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US11/619,299 US8383660B2 (en) 2006-03-10 2007-01-03 Dibenzyl amine compounds and derivatives

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KR101881596B1 (ko) 2008-12-02 2018-07-24 웨이브 라이프 사이언시스 재팬 인코포레이티드 인 원자 변형된 핵산의 합성 방법
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CA2645291C (en) 2011-06-28
BRPI0708753A2 (pt) 2011-06-28
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US20070213314A1 (en) 2007-09-13
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