AR035514A1 - Sales farmaceuticamente aceptables de inhibidores de fosfodiesterasa-4 de 8-arilquinolina sustituida, composiciones farmaceuticas y su uso en la preparacion de medicamentos - Google Patents

Sales farmaceuticamente aceptables de inhibidores de fosfodiesterasa-4 de 8-arilquinolina sustituida, composiciones farmaceuticas y su uso en la preparacion de medicamentos

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Publication number
AR035514A1
AR035514A1 ARP010105722A ARP010105722A AR035514A1 AR 035514 A1 AR035514 A1 AR 035514A1 AR P010105722 A ARP010105722 A AR P010105722A AR P010105722 A ARP010105722 A AR P010105722A AR 035514 A1 AR035514 A1 AR 035514A1
Authority
AR
Argentina
Prior art keywords
alkyl
son
aryl
heteroaryl
halogen
Prior art date
Application number
ARP010105722A
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English (en)
Original Assignee
Merck & Co Inc
Merck Frosst Canada Inc
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 Merck & Co Inc, Merck Frosst Canada Inc filed Critical Merck & Co Inc
Publication of AR035514A1 publication Critical patent/AR035514A1/es

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    • 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
    • C07D401/10—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 aromatic rings
    • 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
    • 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
    • A61P11/02—Nasal agents, e.g. decongestants
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • 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
    • A61P11/14—Antitussive agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • 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
    • A61P17/04—Antipruritics
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/24—Antidepressants
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
    • 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
    • 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
    • C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • 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
    • C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14—Radicals substituted by oxygen 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
    • C07D413/10—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 aromatic 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
    • C07D417/10—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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Neurology (AREA)
  • Pulmonology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Pain & Pain Management (AREA)
  • Diabetes (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Psychiatry (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Vascular Medicine (AREA)
  • Transplantation (AREA)
  • Ophthalmology & Optometry (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Otolaryngology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Una sal farmacéuticamente aceptable de ácido sulfúrico, ácido metansulfónico, ácido p-toluensulfónico, ácido 2-naftalensulfónico, ácido clorhídrico o ácido bencensulfónico, de un compuesto de 8-arilquinolina sustituida representado por la fórmula (1), donde: S1, S2 y S3 son, independientemente, H, -OH, halógeno, alquilo C1-6, -NO2, -CN o alcoxi C1-6, en que los grupos alquilo y alcoxi son sustituidos, optativamente, con 1 a 5 sustituyentes, donde cada sustituyente es, independientemente, un halógeno u OH; R1 es un H, OH, halógeno o grupo carbonilo, alquilo C1-6, cicloalquilo C3-6, alquenilo C1-6, alcoxi C1-6, arilo, heteroarilo, -CN, heterocicloalquilo C3-6, amino, alquilamino C1-6, (alquilo C1-6)(alquil C1-6)amino, alquiloxi C1-6-alquilo C1-6, -C(O)NH(arilo), -C(O)NH(heteroarilo), -SOnNH(arilo), -SOnNH(heteroarilo), -SOnNH(alquilo C1-6), -C(O)n(alquilo C0-6)(alquilo C0-6), -NH-SOn-(alquilo C1-6), -SOn-(alquilo C1-6), -(alquilo C1-6)-O-C(CN)-dialquilamino, o -(alquilo C1-6)-SOn-(alquilo C1-6); donde cualquiera de los grupos es sustituido, optativamente, con 1 a 5 sustituyentes, donde cada sustituyentes es independientemente un halógeno, -OH, -CN, alquilo C1-6, cicloalquilo C3-6, -C(O)(heterocicloalquilo C3-6), -C(O)-O-(alquilo C0-6), -C(O)-ariloxi, alcoxi C1-6, (alquil C0-6)-(alquil C0-6)amino, cicloalquiloxi, acilo, aciloxi, heterocicloalquilo C3-6, arilo, heteroarilo, carbonilo, carbamoílo o -SOn-(alquilo C1-6); A es CH, C-éster o C-R4; R2 y R3 son, independientemente, un grupo arilo, heteroarilo, H, halógeno, -CN, alquilo C1-6, heterocicloalquilo C3-6, alcoxi C1-6, carbonilo, carbamoílo, -C(O)OH, -(alquilo C1-6)-SOn-(alquilo C1-6), -C(O)N(alquilo C0-6)(alquilo C0-6), o alquilacilamino C1-6, donde cualquiera de los grupos es sustituido, optativamente, con 1 a 5 sustituyentes, en que cada sustituyentes es, independientemente, un halógeno, -NO2, -C(O)OH, -CN, N-óxido, -OH o un grupo arilo, heteroarilo, carbonilo, alquilo C1-6, -SOn-(alquilo C1-6), -SOn-(arilo), ariloxi, heteroariloxi, alcoxi C1-6, -C(O)-heterocicloalquilo C3-6, -NH-cicloalquilo C3-6, amino, (C0-6 alquilo)(alquil C0-6)amino o -C(O)-N(alquil C0-6)(alquilo C0-6) sustituyentes, donde cada grupo sustituyente es, independientemente, sustituido optativamente con -OH, alcoxi C1-6, alquilo C1-6, cicloalquilo C3-6, ariloxi, -C(O)OH, -C(O)O(alquilo C1-6), halógeno, -NO2, -CN, -SOn-(alquilo C1-6) o -C(O)-N(alquil C0-6)(alquilo C0-6); uno de R2 y R3 debe ser un arilo o heteroarilo, sustituido optativamente; cuando R2 y R3 son, en ambos casos, un arilo o heteroarilo, entonces R2 y R3 pueden estar optativamente conectados mediante un puente tío, oxi o alquilo C1-4 para formar un sistema de tres anillos fundidos; R4 es un grupo arilo, alquilo C1-6, heteroarilo, -CN, carbonilo, carbamoílo, -(alquil C1-6)-SOn-(alquilo C1-6), -C(O)n(alquil C0-6)(alquilo C0-6) o alquilacilamino C1-6, donde cualquiera de los grupos es sustituido, optativamente, con 1 a 5 sustituyentes, en que cada sustituyentes es, independientemente, un carbonilo, -CN, halógeno, -C(O)(alquilo C0-6), -C(O)O(alquilo C0-6), alquilo C1-6, -SOn-(alquilo C1-6), -OH, alcoxi C1-6 o -(alquil C0-6)(alquil C0-6)amino; n es, independientemente, 0, 1 ó 2; y R2 o R3 puede estar, optativamente, unido a R4 mediante un vínculo para formar un anillo. Estos compuestos son inhibidores de fosfodiesterasa-4 útiles en el tratamiento del asma y la inflamación. Se describen también composiciones farmacéuticas que los contienen y su uso en la preparación de medicamentos.
ARP010105722A 2000-12-20 2001-12-10 Sales farmaceuticamente aceptables de inhibidores de fosfodiesterasa-4 de 8-arilquinolina sustituida, composiciones farmaceuticas y su uso en la preparacion de medicamentos AR035514A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US25680300P 2000-12-20 2000-12-20

Publications (1)

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AR035514A1 true AR035514A1 (es) 2004-06-02

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ARP010105722A AR035514A1 (es) 2000-12-20 2001-12-10 Sales farmaceuticamente aceptables de inhibidores de fosfodiesterasa-4 de 8-arilquinolina sustituida, composiciones farmaceuticas y su uso en la preparacion de medicamentos

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Country Link
US (1) US6740666B2 (es)
EP (1) EP1363635B1 (es)
JP (1) JP2004521921A (es)
KR (1) KR20030063456A (es)
CN (1) CN100508978C (es)
AR (1) AR035514A1 (es)
AT (1) ATE428420T1 (es)
AU (1) AU2001297603B2 (es)
BG (1) BG107900A (es)
BR (1) BR0116372A (es)
CA (1) CA2431549A1 (es)
CZ (1) CZ20031738A3 (es)
DE (1) DE60138421D1 (es)
DO (1) DOP2001000308A (es)
EA (1) EA006607B1 (es)
EE (1) EE200300266A (es)
HU (1) HUP0400654A3 (es)
IL (1) IL156479A0 (es)
JO (1) JO2317B1 (es)
MX (1) MXPA03005673A (es)
MY (1) MY136792A (es)
NO (1) NO20032807L (es)
NZ (1) NZ526376A (es)
PE (1) PE20020787A1 (es)
PL (1) PL362564A1 (es)
SK (1) SK7732003A3 (es)
WO (1) WO2002069970A1 (es)
ZA (1) ZA200304672B (es)

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