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AR035218A1 - Inhibidores vla-4 - Google Patents

Inhibidores vla-4

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Publication number
AR035218A1
AR035218A1 ARP010106105A ARP010106105A AR035218A1 AR 035218 A1 AR035218 A1 AR 035218A1 AR P010106105 A ARP010106105 A AR P010106105A AR P010106105 A ARP010106105 A AR P010106105A AR 035218 A1 AR035218 A1 AR 035218A1
Authority
AR
Argentina
Prior art keywords
group
substituted
unsubstituted
atom
hydrogen atom
Prior art date
Application number
ARP010106105A
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English (en)
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Daiichi Seiyaku Co
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Filing date
Publication date
Application filed by Daiichi Seiyaku Co filed Critical Daiichi Seiyaku Co
Publication of AR035218A1 publication Critical patent/AR035218A1/es

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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles 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 in position 2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
    • 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
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
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    • 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
    • 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
    • C07D413/06—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
    • 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
    • C07D417/06—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
    • C07D417/12—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
    • 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
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    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Hematology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Psychiatry (AREA)
  • Oncology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Transplantation (AREA)
  • Obesity (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Indole Compounds (AREA)

Abstract

Un compuesto representado por la siguiente fórmula (1) [donde, W representa WA-A1-WB- (en el cual WA representa un grupo arilo sustituido o no sustituido o un grupo heterocíclico monovalente sustituido o no sustituido, A1 representa -NR1-, un enlace simple, -C(O)-, -C(O)NR1-, un grupo vinileno sustituido o no sustituido, un grupo etinileno, -CR1aR1b-O-, -CR1a=CR1b-C(O)NR1- o CR1a=CR1b-C(O)-(en el cual R1 representa un átomo de hidrógeno o un grupo alquilo inferior, y R1a y R1b, cada uno representa de manera independiente un átomo de hidrógeno o un grupo alquilo inferior), WB representa un grupo arileno sustituido o no sustituido o un grupo heterocíclico divalente sustituido); R representa un enlace simple, -NH-, -OCH2-, un grupo alquenileno o -(CH2)n-(en el cual, n representa 1 o 2); X representa -C(O)-, -CH2 - o -S(O)2-, y M representa la siguiente fórmula (3), (4) o (5): en la cual (3a) representa un grupo heterocíclico divalente de 4, 5 o 6 miembros (en el cual el átomo de nitrógeno está unido a X y Q representa un átomo de carbono, azufre oxígeno o nitrógeno), R11, R12 y R13 cada uno representa de manera independiente un átomo de hidrógeno, un grupo hidroxilo, un grupo amino, un átomo de halógeno, un grupo ciano, un grupo carboxilo, un grupo alcoxicarbonilo, un grupo carbamoilo, un grupo mono- o dialquilaminocarbonilo sustituido o no sustituido, un grupo alquilo sustituido o no sustituido, un grupo arilo sustituido o no sustituido, un grupo heteroarilo sustituido o no sustituido, un grupo alcoxi sustituido o no sustituido, un grupo mono- o dialquilamino sustituido o no sustituido, un grupo cicloalquilamino sustituido o no sustituido, un grupo alquilsulfonilamino sustituido o no sustituido, un grupo arilsulfonilamino sustituido o no sustituido, un grupo ariloxi, sustituido o no sustituido, un grupo heteroariloxi sustituido o no sustituido, y un grupo benciloxi sustituido o no sustituido, un grupo alquiltio sustituido o no sustituido, un grupo cicloalquiltio sustituido o no sustituido, un grupo ariltio sustituido o no sustituido, un grupo alquilsulfonilo sustituido o no sustituido, un grupo cicloalquilsulfonilo sustituido o no sustituido, o un grupo arilsulfonilo sustituido o no sustituido, o R11, R13 o R12 y R13 se pueden acoplar para formar, junto con el átomo que constituye el grupo heterocíclico al que R12 a R13 están unidos, un hidrocarburo cíclico o heterociclo de 3 a 7 miembros (el hidrocarburo cíclico y el heterociclo pueden tener de 1 a 3 sustituyentes seleccionados de un grupo hidroxilo, átomos de halógeno, un grupo amino, grupos alquilo, grupos alcoxi, grupos arilo, grupos ariloxi, grupos alquilamino, un grupo benciloxi y grupos heteroarilo). R14 representa un átomo de hidrógeno o un alquilo inferior sustituido o no sustituido, Y representa un enlace simple, -C(O)-, -C(O)NH-, o un grupo hidrocarburo alifático divalente lineal o ramificado de C1-12 que puede tener un anillo espiro de C3-6 o puede tener por los menos un -O-, -S-, -S(O)2-, -C(O)- o -NY1- (en la cual Y1 representa un átomo de hidrógeno o un grupo alquilo inferior) en el grupo funcional hidrocarburo en reemplazo del átomo de carbono, Z representa un grupo arileno sustituido o no sustituido, un grupo heteroarileno sustituido o no sustituido o un grupo cicloalquileno sustituido o no sustituido, A2 representa un enlace simple, un grupo alquenileno, un grupo alquinileno, -(CH2)t - o -O(CH2)v-, (en el que t representa 1, 2 o 3 y v representa 0, 1, 2, o 3), y R10 representa un grupo hidroxilo o un grupo alcoxi inferior) de fórmula (4), en el cual fórmula (4a) representa un grupo heterocíclico divalente de 4, 5, 6 o 7 miembros (en el cual el átomo de nitrógeno está unido a X y Q1 representa un átomo de carbono, azufre, oxígeno o nitrógeno), R15 y R16 cada uno representa de manera independiente un átomo de hidrógeno, un grupo hidroxilo, un átomo de halógeno, un grupo amino, un grupo alquilo sustituido o no sustituido o un grupo alcoxi, R16a representa un átomo de hidrógeno o un grupo alquilo sustituido o no sustituido; Y3 representa -O-, -S-, -S(O)2-, -(CH2)fO-, o -NY4- (en la cual f representa 1, 2 o 3 e Y4 representa un átomo de hidrógeno o un grupo alquilo inferior), Z1 representa un grupo arileno sustituido o no sustituido, un grupo heteroarileno sustituido o no sustituido o un grupo cicloalquileno sustituido o no sustituido, A3 representa un enlace simple, un grupo alquenileno, un grupo alquinileno, -(CH2)e- (en el que, e representa 1, 2, o 3), y R17 representa un grupo hidroxilo o un grupo alcoxi inferior), (fórmula 5) (en la cual R18 representa -NR20-(en la cual R20 representa un átomo de hidrógeno, un grupo alquilo sustituido o no sustituido, un grupo cicloalquilo sustituido o no sustituido, un grupo arilo sustituido o no sustituido, un grupo bencilo sustituido o no sustituido, un grupo alquenilo inferior sustituido o no sustituido o un grupo alquinilo sustituido o no sustituido), Z2 representa un grupo hidrocarbonado alifático divalente lineal o ramificado de C1-12 que puede tener un anillo espiro de C3-6, puede tener por lo menos un grupo cicloalquileno de C3-6 en el grupo hidrocarbonado en reemplazo del átomo de carbono o puede tener por lo menos un -O-, -S-, -S(O)2-, -C(O)- o -NR21-(en la cual R21 representa un átomo de hidrógeno o un grupo alquilo inferior sustituido o no sustituido en el grupo funcional hidrocarburo en reemplazo del átomo de carbono, Q2 representa un enlace simple, un grupo arileno sustituido o no sustituido, un grupo heteroarileno sustituido o no sustituido o un grupo cicloalquileno sustituido o no sustituido, L representa un enlace simple, o un grupo alquileno inferior sustituido o no sustituido o un grupo alquinileno inferior sustituido o no sustituido, o R19 representa un grupo hidroxi o un grupo alcoxi inferior)]; o una sal del mismo. Un producto farmacéutico que comprende un compuesto de fórmula (1) o sal del mismo, útil como preventivo o remedio de una enfermedad causada por adhesión celular que se selecciona entre enfermedades inflamatorias, autoinmunes, metástasis, asma bronquial, rinostenosis, diabetes, artritis, psoriasis, esclerosis múltiple, enfermedades intestinales inflamatorias y rechazo al trasplante. Una composición farmacéutica que comprende un vehículo farmacéuticamente aceptable y un compuesto de fórmula (1) o su sal.
ARP010106105A 2000-12-28 2001-12-28 Inhibidores vla-4 AR035218A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000402890 2000-12-28
JP2001149923 2001-05-18

Publications (1)

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AR035218A1 true AR035218A1 (es) 2004-05-05

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US (1) US7157487B2 (es)
EP (1) EP1346982B1 (es)
JP (1) JP4212358B2 (es)
KR (1) KR100884877B1 (es)
CN (1) CN100471838C (es)
AR (1) AR035218A1 (es)
AT (1) ATE524441T1 (es)
AU (1) AU2002219555B2 (es)
BR (1) BR0116608A (es)
CA (1) CA2430978C (es)
IL (1) IL156064A0 (es)
MX (1) MXPA03005838A (es)
NO (1) NO326014B1 (es)
RU (1) RU2290403C2 (es)
TW (1) TWI312779B (es)
WO (1) WO2002053534A1 (es)

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