AR052223A1 - Metodods y composiciones que utilizan moduladores de pde4 para eltratamiento y el manejo de lesiones del sistema nervioso central - Google Patents

Metodods y composiciones que utilizan moduladores de pde4 para eltratamiento y el manejo de lesiones del sistema nervioso central

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Publication number
AR052223A1
AR052223A1 ARP050104509A ARP050104509A AR052223A1 AR 052223 A1 AR052223 A1 AR 052223A1 AR P050104509 A ARP050104509 A AR P050104509A AR P050104509 A ARP050104509 A AR P050104509A AR 052223 A1 AR052223 A1 AR 052223A1
Authority
AR
Argentina
Prior art keywords
alkyl
hydrogen
phenyl
cyano
alkoxy
Prior art date
Application number
ARP050104509A
Other languages
English (en)
Original Assignee
Celgene 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 Celgene Corp filed Critical Celgene Corp
Publication of AR052223A1 publication Critical patent/AR052223A1/es

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Classifications

    • 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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A61K31/515—Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Neurosurgery (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Métodos para tratar, prevenir y/o manejar una lesion/dano del sistema nervioso central y síndromes relacionados. Los métodos específicos abarcan la administracion de un modulador de PDE4 solo o en combinacion con un segundo agente activo. También las composiciones farmacéuticas, las formas de dosificacion unitarias, y los equipos adecuados para usar en los métodos. Reivindicacion 10: El método de acuerdo con las reivindicaciones 1, 2, 5 o 6, caracterizado porque el modulador de PDE4 es 3- (3,4- dimetoxi-fenil)-3-(1-oxo-1,3-dihidro-isoindol-2-il)propionamida. Reivindicacion 11: El método de acuerdo con la reivindicacion 10, caracterizado porque el modulador de PDE4 es R o S 3-(3,4-dimetoxi- fenil)-3-(1-oxo-1,3-dihidro-isoindol-2- il)propionamida enantioméricamente pura. Reivindicacion 12: El método de acuerdo con las reivindicaciones 1, 2, 5 o 6, caracterizado porque el modulador de PDE4 es {2-[1-(3- etoxi-4-metoxi-fenil)-2-metansulfonil-etil]-3-oxo-2,3-dihidro-1H-isoindol-4- il}-amida del ácido ciclopropancarboxílico. Reivindicacion 14: El método de acuerdo con las reivindicaciones 1, 2, 5 o 6, caracterizado porque el modulador de PDE4 tiene la formula (1), en donde n tiene un valor de 1, 2 o 3; R5 es O-fenileno, no sustituido o sustituido con 1 a 4 sustituyentes cada uno seleccionado, de modo independiente, del grupo que consiste en nitro, ciano, trifluorometilo, carbetoxi, carbometoxi, carbopropoxi, acetilo, carbamoilo, acetoxi, carboxi, hidroxi, amino, alquilamino, dialquilamino, acilamino, alquilo C1-10, alquilo C1-10 y halo; R7 es i) fenilo o fenilo sustituido con uno o varios sustituyentes seleccionados cada uno, de modo independiente, del grupo que consiste en de nitro, ciano, trifluorometilo, carbetoxi, carbometoxi, carbopropoxi, acetilo, carbamoilo, acetoxi, carboxi, hidroxi, amino, alquilo C1-10, alcoxi C1-10 y halo, ii) bencilo no sustituido o sustituido con 1 a 3 sustituyentes seleccionados del grupo que consiste en nitro, ciano, trifluorometilo, carbotoxi, carbometoxi, carbopropoxi, acetilo, carbamoilo, acetoxi, carboxi, hidroxi, amino, alquilo C1-10, alcoxi C1-10 y halo, iii) naftilo y iv) benciloxi; R12 es -OH, alcoxi C1-12; o -(R8)(R9); R8 es hidrogeno o alquilo C1-10; y R9 es hidrogeno, alquilo C1-10, -COR10 o - SO2R10, en donde R10 es hidrogeno, alquilo C1-10 o fenilo. Reivindicacion 16: El método de acuerdo con las reivindicaciones 1, 2, 5 o 6, caracterizado porque el modulador de PDE4 tiene la formula (2), en donde cada uno de R1 y R2, cuando se toman de modo independiente entre sí, hidrogeno, inferior alquilo o R1 y R2, cuando se toman junto con los átomos de carbono representados a los que cada uno está unido, es O-fenileno, O-naftileno o ciclohexen- 1,2-diílo, no sustituido o sustituido con 1 a 4 sustituyentes cada uno seleccionado, de modo independiente, del grupo que consiste en nitro, ciano, trifluorometilo, carbetoxi, carbometoxi, carbopropoxi, acetilo, carbamoilo, acetoxi, carboxi, hidroxi, amino, alquilamino, dialquilamino, acilamino, alquilo C1-10, alcoxi C1-10 y halo; R3 es fenilo sustituido con uno a cuatro sustituyentes seleccionados del grupo que consiste en nitro, ciano, trifluorometilo, carbetoxi, carbometoxi, carbopropoxi, acetilo, carbamoilo, acetoxi, carboxi, hidroxi, amino, alquilo C1-10, alcoxi C1-10, alquiltio C1-10, benciloxi, cicloalcoxi C3-6, cicloalquilidenmetilo C4-6, alquildenmetilo C3-10, indaniloxi y halo; R4 es hidrogeno, alquilo C1-6, fenilo o bencilo; R4' es hidrogeno o alquilo C1-6; R5 -CH2-, -CH2-CO-, SO2-, -S- o -NHCO; y n tiene un valor de 0, 1 o 2. Reivindicacion 18: El método de acuerdo con las reivindicaciones 1, 2, 5 o 6, caracterizado porque el modulador de PDE4 tiene la formula (3), en donde el átomo de carbono designado con * constituye un centro de quiralidad; Y es C=O, CH2, SO2 o CH2C=O; cada uno de R1, R2, R3 y R4, de modo independiente entre sí, es hidrogeno, halo, alquilo C1-4, alcoxi C1-4, nitro, ciano, hidroxi o -NR8R9; o dos indistintos de R1, R2 R3 y R4 en átomos de carbono adyacentes, junto con el anillo fenileno representado son naftilideno; cada uno de R5 y R6, de modo independiente entre sí, es hidrogeno, alquilo C1-4, alcoxi C1-4, ciano o cicloalcoxi de hasta 18 átomos de carbono; R7 es hidroxi, alquilo C1-8, fenilo bencilo o NR8'R9'; cada uno de R8 y R9 tomado de modo independiente entre sí es hidrogeno, alquilo C1-8, fenilo o bencilo o uno de R8 y R9 es hidrogeno y el otro es - COR10 o -SO2R10 o R8 y R9 tomados juntos son tetrametileno, pentametileno, hexametileno o -CH2CH2X1CH2CH2-, en donde X1 es -O-, -S- o -NH-; y cada uno de R8' y R9' tomado de modo independiente entre sí es hidrogeno, alquilo C1-8, fenilo o bencilo o uno de R8' y R9' es hidrogeno y el otro es -COR10' o -SO2R10' o R8' y R9' tomados juntos son tetrametileno, pentametileno, hexametileno o -CH2CH2X2CH2-CH2-, en donde X2 es -O-, -S- o -NH-.
ARP050104509A 2004-10-28 2005-10-27 Metodods y composiciones que utilizan moduladores de pde4 para eltratamiento y el manejo de lesiones del sistema nervioso central AR052223A1 (es)

Applications Claiming Priority (1)

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US62380304P 2004-10-28 2004-10-28

Publications (1)

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AR052223A1 true AR052223A1 (es) 2007-03-07

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ID=36319648

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Country Status (14)

Country Link
US (1) US20060106085A1 (es)
EP (1) EP1811992A2 (es)
JP (1) JP2008518924A (es)
KR (1) KR20070085454A (es)
CN (1) CN101309585A (es)
AR (1) AR052223A1 (es)
AU (1) AU2005302523A1 (es)
BR (1) BRPI0518062A (es)
CA (1) CA2585423A1 (es)
IL (1) IL182825A0 (es)
MX (1) MX2007005040A (es)
PE (1) PE20061167A1 (es)
WO (1) WO2006050057A2 (es)
ZA (1) ZA200704251B (es)

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Also Published As

Publication number Publication date
BRPI0518062A (pt) 2008-10-28
CA2585423A1 (en) 2006-05-11
KR20070085454A (ko) 2007-08-27
WO2006050057A3 (en) 2008-07-10
MX2007005040A (es) 2007-06-19
CN101309585A (zh) 2008-11-19
ZA200704251B (en) 2008-11-26
EP1811992A2 (en) 2007-08-01
IL182825A0 (en) 2007-09-20
WO2006050057A2 (en) 2006-05-11
JP2008518924A (ja) 2008-06-05
AU2005302523A1 (en) 2006-05-11
PE20061167A1 (es) 2006-11-08
US20060106085A1 (en) 2006-05-18

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