ES2580803T3 - Moduladores de transportadores del casete de unión a ATP - Google Patents

Moduladores de transportadores del casete de unión a ATP Download PDF

Info

Publication number
ES2580803T3
ES2580803T3 ES13167785.8T ES13167785T ES2580803T3 ES 2580803 T3 ES2580803 T3 ES 2580803T3 ES 13167785 T ES13167785 T ES 13167785T ES 2580803 T3 ES2580803 T3 ES 2580803T3
Authority
ES
Spain
Prior art keywords
optionally substituted
independently
ring
carboxylic acid
aliphatic
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
ES13167785.8T
Other languages
English (en)
Inventor
Sara S. Hadida Ruah
Peter D.J. Grootenhuis
Fredrick Van Goor
Jinglan Zhou
Brian Bear
Mark T. Miller
Jason Mccartney
Mehdi Michel Jamel Numa
Xiaoqing Yang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vertex Pharmaceuticals Inc
Original Assignee
Vertex Pharmaceuticals 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 Vertex Pharmaceuticals Inc filed Critical Vertex Pharmaceuticals Inc
Application granted granted Critical
Publication of ES2580803T3 publication Critical patent/ES2580803T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • 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
    • A61P11/08—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
    • A61P11/12—Mucolytics
    • 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
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • A61P25/28—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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/04—Artificial tears; Irrigation solutions
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • 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
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61P7/10—Antioedematous agents; Diuretics
    • 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
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/002—Heterocyclic compounds
    • 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
    • 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
    • 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
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/10—Screening for compounds of potential therapeutic value involving cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Neurosurgery (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cell Biology (AREA)
  • Epidemiology (AREA)
  • Obesity (AREA)
  • Pulmonology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Biotechnology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Psychology (AREA)
  • Pain & Pain Management (AREA)

Abstract

Un compuesto de fórmula Ic:**Fórmula** o una sal farmacéuticamente aceptable del mismo, en la que R1 es -ZAR4, en el que cada ZA es independientemente un enlace o una cadena alifática C1-6 ramificada o lineal opcionalmente sustituida en la que hasta dos unidades de carbono de ZA están opcional e independientemente sustituidas con -CO-, -CS-, -CONRA-, -CONRANRA-, -CO2- -OCO-, -NRACO2-, -O-, -NRACONRA-, -OCONRA-, - NRANRA-, -NRACO-, -S-, -SO-, -SO2- -NRA-, -SO2NRA-, -NRASO2- o -NRASO2NRA-, Cada R4 es independientemente RA, halógeno, -OH, -NH2, -NO2, -CN o -OCF3, Cada RA es independientemente hidrógeno, un alifático opcionalmente sustituido, un cicloalifático opcionalmente sustituido, un heterocicloalifático opcionalmente sustituido, un arilo opcionalmente sustituido o un heteroarilo opcionalmente sustituido; Cada R2 es independientemente -ZBR5, en el que cada ZB es independientemente un enlace o una cadena alifática C1-6 ramificada o lineal opcionalmente sustituida en la que hasta dos unidades de carbono de ZB están opcional e independientemente sustituidas con -CO-, -CS-, -CONRB-, -CONRBNRB-, -CO2-, -OCO-, -NRBCO2-, - O-, -NRBCONRB-, -OCONRB-, -NRBNRB-, -NRBCO-, -S-, -SO-, -SO2-, -NRB-, -SO2NRB-, -NRBSO2- o - NRBSO2NRB-, Cada R5 es independientemente RB30 , halógeno, -OH, -NH2, -NO2, -CN, -CF3 o -OCF3, Cada RB es independientemente hidrógeno, un alifático opcionalmente sustituido, un cicloalifático opcionalmente sustituido, un heterocicloalifático opcionalmente sustituido, un arilo opcionalmente sustituido, o un heteroarilo opcionalmente sustituido; o, dos grupos R2 cualquiera adyacentes junto con los átomos a los que están unidos forman un carbociclo opcionalmente sustituido o un heterociclo opcionalmente sustituido; El Anillo A es un anillo monocíclico de 3-7 miembros que tiene 0-3 heteroátomos seleccionados de N, O y S; El Anillo B es un grupo que tiene la fórmula Ia:**Fórmula** o una sal farmacéuticamente aceptable del mismo, en la que p es 0-2, Cada R3 y R'3 es independientemente -ZCR6, en el que cada ZC es independientemente un enlace o una cadena alifática C1-6 ramificada o lineal opcionalmente sustituidaen la que hasta dos unidades de carbono de ZC están opcional e independientemente sustituidas con -CO-, -CS-, -CONRC-, -CONRCNRC-, -CO2-, - OCO-, -NRCCO2-, -O-, -NRCCONRC-, -OCONRC-, -NRCNRC-, -NRCCO-, -S-, -SO-, -SO2-, -NRC-, -SO2NRC-, - NRCSO2- o -NRCSO2NRC-, Cada R6 es independientemente RC, halógeno, -OH, -NH2, -NO2, -CN o -OCF3, Cada RC es independientemente hidrógeno, un alifático opcionalmente sustituido, un cicloalifático opcionalmente sustituido,un heterocicloalifático opcionalmente sustituido, un arilo opcionalmente sustituido o un heteroarilo opcionalmente sustituido, o, dos grupos R3 cualquiera adyacentes junto con los átomos a los que están unidos forman un heterociclo opcionalmente sustituido; y n es 1-3, a condición de que Cuando el anillo A es ciclopentilo sin sustituir, n es 1, R2 es 4-cloro y R1 es hidrógeno, entonces el anillo B no es 2-(terc-butil)indol-5-ilo, o (2,6-diclorofenil(carbonil))-3-metil-1H-indol-5-ilo; y cuando el anillo A es ciclopentilo sin sustituir, n es 0 y R1 es hidrógeno, entonces el anillo B no es**Fórmula** para su uso en el tratamiento de la infertilidad masculina o insuficiencia pancreática.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
imagen8
imagen9
imagen10
imagen11
imagen12
imagen13
5
15
25
35
45
55
65
En otras realizaciones, R1 es -ZAR4, en el que cada ZA es un enlace y cada R4 es hidrógeno.
2. Grupo R2
Cada R2 es independientemente -ZBR5, en el que cada ZB es independientemente un enlace o una cadena alifática C1-6 ramificada o lineal opcionalmente sustituida en la que hasta dos unidades de carbono de ZB están opcionalmente e independientemente sustituidas con -CO-, -CS-, -CONRB-, -CONRBNRB-, -CO2-, -OCO-, -NRBCO2-, -O-, -NRBCONRB-, -OCONRB-, -NRBNRB-, -NRBCO-, -S-, -SO-, -SO2-, -NRB-, -SO2NRB-, -NRBSO2-o -NRBSO2NRB-.
RB RB
Cada R5 es independientemente , halógeno, -OH,-NH2, -NO2, -CN, -CF3, o -OCF3. Cada es independientemente hidrógeno, un alifático opcionalmente sustituido, un cicloalifático opcionalmente sustituido, un heterocicloalifático opcionalmente sustituido, un arilo opcionalmente sustituido o un heteroarilo opcionalmente sustituido. Alternativamente, dos grupos R2 cualquiera adyacentes junto con los átomos a los que están unidos forman un carbociclo opcionalmente sustituido o un heterociclo o heteroarilo opcionalmente sustituido.
En varias realizaciones, R2 es un alifático opcionalmente sustituido. Por ejemplo, R2 es una cadena alifática C1-6 ramificada o lineal opcionalmente sustituida. En otros ejemplos, R2 es una cadena de alquilo C1-6 ramificada o lineal opcionalmente sustituida, una cadena de alquenilo C2-6 ramificada o lineal opcionalmente sustituida, o una cadena de alquinilo C2-6 ramificada o lineal opcionalmente sustituida. En realizaciones alternativas, R2 es una cadena alifática C1-6 ramificada o lineal que está opcionalmente sustituida con 1-3 de halógeno, hidroxi, ciano, cicloalifático, heterocicloalifático, arilo, heteroarilo, o combinaciones de los mismos. Por ejemplo, R2 es un alquilo C1-6 ramificado o lineal que está opcionalmente sustituido con 1-3 de halógeno, hidroxi, ciano, cicloalifático, heterocicloalifático, arilo, heteroarilo, o combinaciones de los mismos. En todavía otros ejemplos, R2 es un metilo, etilo, propilo, butilo, isopropilo o terc-butilo, cada uno de los cuales está opcionalmente sustituido con 1-3 de halógeno, hidroxi, ciano, arilo, heteroarilo, cicloalifático o heterocicloalifático. En todavía otros ejemplos, R2 es un metilo, etilo, propilo, butilo, isopropilo o terc-butilo, cada uno de los cuales está sin sustituir.
En varias otras realizaciones, R2 es un alcoxi C1-5 ramificado o lineal opcionalmente sustituido. Por ejemplo, R2 es un alcoxi C1-5 que está opcionalmente sustituido con 1-3 de hidroxi, arilo, heteroarilo, cicloalifático, heterocicloalifático o combinaciones de los mismos. En otros ejemplos, R2 es un metoxi, etoxi, propoxi, butoxi o pentoxi, cada uno de los cuales está opcionalmente sustituido con 1-3 de hidroxi, arilo, heteroarilo, cicloalifático, heterocicloalifático, o combinaciones de los mismos.
En otras realizaciones, R2 es hidroxi, halógeno o ciano.
En varias realizaciones, R2 es -ZBR5, y ZB es independientemente un enlace o una cadena alifática C1-4 ramificada o lineal opcionalmente sustituida en la que hasta dos unidades de carbono de ZB están opcionalmente e independientemente sustituidas con -C(O)-, -O-, -S-, -S(O)2-o -NH-, y R5 es RB, halógeno, -OH, -NH2, -NO2, -CN, -CF3 o -OCF3, y RB es hidrógeno o arilo.
En varias realizaciones, dos grupos R2 adyacentes forman un carbociclo opcionalmente sustituido o un heterociclo opcionalmente sustituido. Por ejemplo, dos grupos R2 adyacentes forman un carbociclo opcionalmente sustituido o un heterociclo opcionalmente sustituido, cualquiera de los cuales está condensado con el fenilo de fórmula I, en el que el carbociclo o heterociclo tiene la fórmula Ib:
imagen14
Cada uno de Z1, Z2, Z3, Z4 y Z5 es independientemente un enlace, -CR7R'7-, -C(O)-, -NR7-o -O-; cada R7 es independientemente -ZDR8, en el que cada ZD es independientemente un enlace o una cadena alifática C1-6 ramificada o lineal opcionalmente sustituida en la que hasta dos unidades de carbono de ZD están opcionalmente e independientemente sustituidas con -CO-, -CS-, -CONRD-, -CO2-, -OCO-, -NRDCO2-, -O-, -NRDCONRD-, -OCONRD-, -NRDNRD-, -NRDCO-, -S-, -SO-, -SO2-, -NRD-, -SO2NRD-, -NRDSO2-o -NRDSO2NRD-. Cada R8 es independientemente RD, halógeno, -OH, -NH2, -NO2, -CN,-CF3 o -OCF3. Cada RD es independientemente hidrógeno, un cicloalifático opcionalmente sustituido, un heterocicloalifático opcionalmente sustituido, un arilo opcionalmente sustituido o un heteroarilo opcionalmente sustituido. Cada R'7 es independientemente hidrógeno, alifático C1-6 opcionalmente sustituido, hidroxi, halógeno, ciano, nitro, o combinaciones de los mismos. Alternativamente, dos grupos R7 cualquiera adyacentes junto con los átomos a los que están unidos forman un anillo carbocíclico de 3-7 miembros opcionalmente sustituido, tal como un anillo de ciclobutilo opcionalmente sustituido, o dos grupos R7 y R'7 cualquiera junto con el átomo o átomos a los que están unidos forman un anillo carbocíclico o un anillo
15
imagen15
imagen16
imagen17
imagen18
imagen19
imagen20
imagen21
imagen22
imagen23
imagen24
imagen25
imagen26
imagen27
imagen28
imagen29
imagen30
imagen31
imagen32
imagen33
imagen34
imagen35
imagen36
imagen37
imagen38
imagen39
imagen40
imagen41
imagen42
imagen43
imagen44
imagen45
imagen46
imagen47
imagen48
imagen49
imagen50
imagen51
imagen52
imagen53
imagen54
imagen55
imagen56
imagen57
imagen58
imagen59
imagen60
imagen61
imagen62
imagen63
imagen64
imagen65
imagen66
imagen67
imagen68
imagen69
imagen70
imagen71
imagen72
imagen73
imagen74
imagen75
imagen76
imagen77
imagen78
imagen79
imagen80
imagen81
imagen82
imagen83
imagen84
imagen85
imagen86
imagen87
imagen88
imagen89
imagen90
imagen91
imagen92
imagen93
imagen94
imagen95
imagen96
imagen97
imagen98
imagen99
imagen100
imagen101
imagen102
imagen103
5
6-Clorometil-2,3-dihidro-benzo[1,4]dioxina
Se agitó una mezcla de (2,3-dihidro-benzo[1,4]dioxin-6-il)metanol (10,6 g) en SOCl2 (10 ml) a temperatura ambiente durante 10 min y luego se vertió en agua con hielo. Se separó la fase orgánica y la fase acuosa se extrajo
10 con diclorometano (50 ml × 3). Las fases orgánicas combinadas se lavaron con NaHCO3 (disolución sat), agua y salmuera, se secaron sobre Na2SO4 y se concentraron a sequedad para obtener 6-clorometil-2,3-dihidrobenzo[1,4]dioxina (12 g, 88 % durante dos etapas), que se usó directamente en la siguiente etapa.
imagen104
2-(2,3-Dihidrobenzo[b][1,4]dioxin-6-il)acetonitrilo
20 Se agitó una mezcla de 6-clorometil-2,3-dihidro-benzo[1,4]dioxina (12,5 g, 67,7 mmoles) y NaCN (4,30 g, 87,8 mmoles) en DMSO (50 ml) a ta durante 1 h. La mezcla se vertió en agua (150 ml) y a continuación se extrajo con diclorometano (50 ml × 4). Las fases orgánicas combinadas se lavaron con agua (50 ml × 2) y salmuera (50 ml), se secaron sobre Na2SO4 y se concentraron a sequedad. El residuo se purificó por columna (éter de petróleo/acetato de etilo 50:1) sobre gel de sílice para obtener 2-(2,3-dihidrobenzo[b][1,4]dioxin-6-il)acetonitrilo como un aceite
25 amarillo (10,2 g, 86 %), RMN 1H (300 MHz, CDCl3) δ 6,78-6,86 (m, 3H), 4,25 (s, 4H), 3,63 (s, 2H).
La siguiente Tabla 2 contiene una lista de elementos estructurales de ácido carboxílico que estuvieron comercialmente disponibles, o se prepararon por uno de los tres métodos descritos anteriormente:
30 Tabla 2: Elementos estructurales de ácido carboxílico.
35
40
45
50
55
60
65
Nombre
Estructura
1-benzo[1,3]dioxol-5-ilciclopropano-1-ácido carboxílico
imagen105
1-(2,2-difluorobenzo[1,3]dioxol-5-il)ciclopropano-1-ácido carboxílico
imagen106
1-(3,4-dihidroxifenil)ciclopropano acido carboxílico
imagen107
1-(3-metoxifenil)ciclopropano-1-ácido carboxilico
imagen108
1-(2-metoxifenil)ciclopropano-1-ácido carboxílico
imagen109
1-[4-(trifluorometoxi)fenil]ciclopropano-1-ácido carboxílico
imagen110
1-(2,2-dimetilbenzo[d][1,3]dioxol-5-il)ciclopropano ácido carboxílico
imagen111
104
5
10
15
20
25
30
35
40
45
50
55
60
65
Nombre
Estructura
tetrahidro-4-(4-metoxifenil)-2H-piran-4-ácido carboxílico
imagen112
1-fenilciclopropano-1-ácido carboxílico
imagen113
1-(4-metoxifenil)ciclopropano-1-ácido carboxílico
imagen114
1-(4-clorofenil)ciclopropano-1-ácido carboxílico
imagen115
1-(3-hidroxifenil)ciclopropano ácido carboxílico
imagen116
1-fenilciclopentano ácido carboxílico
imagen117
1-(2-oxo-2,3-dihidrobenzo[d]oxazol-5-il)ciclopropano ácido carboxílico
imagen118
1-(benzofuran-5-il)ciclopropano ácido carboxílico
imagen119
1-(4-metoxifenil)ciclohexano ácido carboxílico
imagen120
1-(4-clorofenil)ciclohexano ácido carboxílico
imagen121
1-(2,3-dihidrobenzofuran-5-il)ciclopropano ácido carboxílico
imagen122
1-(3,3-dimethil-2,3-dihidrobenzofuran-5-il)ciclopropano ácido carboxílico
imagen123
105
5
10
15
20
25
30
35
40
45
50
55
60
Nombre
Estructura
1-(7-metoxibenzo[d][1,3]dioxol-5-il)ciclopropano ácido carboxílico
imagen124
1-(3-hidroxi-4-metoxifenil)ciclopropano ácido carboxílico
imagen125
1-(4-cloro-3-hidroxifenil)ciclopropano ácido carboxílico
imagen126
1-(3-(benziloxi)-4-clorofenil)ciclopropano ácido carboxílico
imagen127
1-(4-clorofenil)ciclopentano ácido carboxílico
imagen128
1-(3-(benziloxi)-4-metoxifenil)ciclopropano ácido carboxílico
imagen129
1-(3-cloro-4-metoxifenil)ciclopropano ácido carboxílico
imagen130
1-(3-fluoro-4-metoxifenil)ciclopropano ácido carboxílico
imagen131
1-(4-metoxi-3-metilfenil)ciclopropano ácido carboxílico
imagen132
1-(4-(benziloxi)-3-metoxifenil)ciclopropano ácido carboxílico
imagen133
1-(4-cloro-3-metoxifenil)ciclopropano ácido carboxílico
imagen134
1-(3-cloro-4-hidroxifenil)ciclopropano ácido carboxílico
imagen135
106
5
10
15
20
25
30
35
40
45
50
55
60
Nombre
Estructura
1-(3-(hidroximetil)-4-metoxifenil)ciclopropano ácido carboxilico
imagen136
1-(4-metoxifenil)ciclopentano ácido carboxilico
imagen137
1-fenilciclohexano ácido carboxilico
imagen138
1-(3,4-dimetoxifenil)ciclopropano ácido carboxilico
imagen139
1-(7-chlorobenzo[d][1,3]dioxol-5-il)ciclopropano ácido carboxilico
imagen140
1-(benzo[djoxazol-5-il)ciclopropano ácido carboxilico
imagen141
1-(7-fluorobenzo[d][1,3]dioxol-5-il)ciclopropano ácido carboxilico
imagen142
1-(3,4-difluorofenil)ciclopropano ácido carboxilico
imagen143
1-(1H-indol-5-il)ciclopropano ácido carboxilico
imagen144
1-(1H-benzo[d]imidazol-5-il)ciclopropano ácido carboxilico
imagen145
1-(2-metil-1H-benzo[d]imidazol-5-il)ciclopropano ácido carboxilico
imagen146
1-(-metil-1H-benzo[d]imidazol-5-il)ciclopropano ácido carboxilico
imagen147
1-(3-metilbenzo[d]isoxazol-5-il)ciclopropano ácido carboxilico
imagen148
107
5
10
15
20
25
30
35
40
45
50
55
60
65
Nombre
Estructura
1-(spiro[benzo[d][1,3]dioxol-2,1’-ciclobutano]-5-il)ciclopropano ácido carboxílico
imagen149
1-(1H-benzo[d][1,2,3]triazol-5-il)ciclopropano ácido carboxílico
imagen150
1-(1-metil-1H-benzo[d][1,2,3]triazol-5-il)ciclopropano ácido carboxílico
imagen151
1-(1,3-dihidroisobenzofuran-5-il)ciclopropano ácido carboxílico
imagen152
1-(6-fluorobenzo[d][1,3]dioxol-5-il)ciclopropano ácido carboxílico
imagen153
1-(2,3-dihidrobenzofuran-6-il)ciclopropano ácido carboxílico
imagen154
1-(chroman-6-il)ciclopropano ácido carboxílico
imagen155
1-(4-hidroxy-4-methoxychroman-6-il)ciclopropano ácido carboxílico
imagen156
1-(4-oxochroman-6-il)ciclopropano ácido carboxílico
imagen157
1-(3,4-dicloorofenil)ciclopropano ácido carboxílico
imagen158
1-(2,3-dihidrobenzo[b][1,4]dioxin-6-il)ciclopropano ácido carboxílico
imagen159
1-(benzofuran-6-il)ciclopropano ácido carboxílico
imagen160
108
imagen161
imagen162
imagen163
imagen164
imagen165
imagen166
imagen167
imagen168
imagen169
imagen170
imagen171
imagen172
imagen173
imagen174
imagen175
imagen176
imagen177
imagen178
imagen179
imagen180
imagen181
imagen182
imagen183
imagen184
imagen185
imagen186
imagen187
imagen188
imagen189
imagen190
imagen191
imagen192
imagen193
imagen194
imagen195
imagen196
imagen197
imagen198
imagen199
imagen200
imagen201
imagen202
imagen203
imagen204
imagen205
imagen206
imagen207
imagen208
imagen209
imagen210
imagen211
imagen212
imagen213
imagen214
imagen215
imagen216
imagen217
imagen218
imagen219
imagen220
imagen221
imagen222
imagen223
imagen224
imagen225
imagen226
imagen227
imagen228
imagen229
imagen230
imagen231
imagen232
imagen233
imagen234
imagen235
imagen236
imagen237
imagen238
imagen239
imagen240
imagen241
imagen242
imagen243
imagen244
imagen245

Claims (1)

  1. imagen1
    imagen2
    imagen3
    imagen4
    imagen5
    imagen6
    imagen7
    imagen8
    201
    imagen9
    imagen10
    imagen11
    imagen12
    imagen13
    imagen14
    imagen15
    60
    65
    208
    imagen16
    imagen17
    imagen18
    imagen19
    imagen20
    213
    imagen21
    imagen22
    imagen23
    imagen24
    imagen25
    imagen26
    imagen27
    imagen28
ES13167785.8T 2006-04-07 2007-04-09 Moduladores de transportadores del casete de unión a ATP Active ES2580803T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US79045906P 2006-04-07 2006-04-07
US790459P 2006-04-07

Publications (1)

Publication Number Publication Date
ES2580803T3 true ES2580803T3 (es) 2016-08-26

Family

ID=38477342

Family Applications (4)

Application Number Title Priority Date Filing Date
ES13167785.8T Active ES2580803T3 (es) 2006-04-07 2007-04-09 Moduladores de transportadores del casete de unión a ATP
ES16155334.2T Active ES2659364T3 (es) 2006-04-07 2007-04-09 Moduladores de transportadores del casete de unión a ATP
ES07755298.2T Active ES2554353T3 (es) 2006-04-07 2007-04-09 Moduladores de transportadores del casete de unión a ATP
ES17209175T Active ES2882684T3 (es) 2006-04-07 2007-04-09 Preparación de moduladores de transportadores del casete de unión a ATP

Family Applications After (3)

Application Number Title Priority Date Filing Date
ES16155334.2T Active ES2659364T3 (es) 2006-04-07 2007-04-09 Moduladores de transportadores del casete de unión a ATP
ES07755298.2T Active ES2554353T3 (es) 2006-04-07 2007-04-09 Moduladores de transportadores del casete de unión a ATP
ES17209175T Active ES2882684T3 (es) 2006-04-07 2007-04-09 Preparación de moduladores de transportadores del casete de unión a ATP

Country Status (22)

Country Link
US (9) US7776905B2 (es)
EP (5) EP2674428B1 (es)
JP (3) JP5420395B2 (es)
CN (2) CN103254177A (es)
AU (1) AU2007235260B2 (es)
BR (1) BRPI0710965B8 (es)
CA (2) CA2869945C (es)
CY (3) CY1116979T1 (es)
DK (3) DK2007756T3 (es)
ES (4) ES2580803T3 (es)
HU (4) HUE027630T2 (es)
IL (1) IL194576A (es)
IN (1) IN2014KN02423A (es)
LT (1) LT3091011T (es)
MX (1) MX2008012945A (es)
NZ (3) NZ571803A (es)
PL (4) PL3091011T3 (es)
PT (3) PT2007756E (es)
RU (1) RU2451018C2 (es)
SI (4) SI3091011T1 (es)
WO (1) WO2007117715A2 (es)
ZA (1) ZA200809290B (es)

Families Citing this family (116)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2006111093A (ru) 2003-09-06 2007-10-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Модуляторы атр-связывающих кассетных транспортеров
CN101675928A (zh) * 2003-11-14 2010-03-24 沃泰克斯药物股份有限公司 可用作atp-结合弹夹转运蛋白调控剂的噻唑和噁唑
US7977322B2 (en) 2004-08-20 2011-07-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
BRPI0507278A (pt) * 2004-01-30 2007-06-26 Vertex Pharma moduladores dos transportadores do cassete de ligação ao atp
RS56037B1 (sr) 2004-06-24 2017-09-29 Vertex Pharma Modulatori atp-vezujućih kasetnih transportera
US7999113B2 (en) 2005-08-11 2011-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
CN102775396B (zh) 2005-11-08 2014-10-08 沃泰克斯药物股份有限公司 Atp-结合弹夹转运蛋白的杂环调控剂
US7671221B2 (en) * 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
EP3219705B1 (en) 2005-12-28 2020-03-11 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions of the amorphous form of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
CA2856037C (en) 2005-12-28 2017-03-07 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
EP2674428B1 (en) 2006-04-07 2016-04-06 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
US7645789B2 (en) * 2006-04-07 2010-01-12 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
US10022352B2 (en) 2006-04-07 2018-07-17 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
USRE50453E1 (en) 2006-04-07 2025-06-10 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
NZ576642A (en) * 2006-11-03 2011-11-25 Vertex Pharma Azaindole derivatives as cftr modulators
US8563573B2 (en) * 2007-11-02 2013-10-22 Vertex Pharmaceuticals Incorporated Azaindole derivatives as CFTR modulators
US7754739B2 (en) * 2007-05-09 2010-07-13 Vertex Pharmaceuticals Incorporated Modulators of CFTR
EP2142498A2 (en) * 2007-04-02 2010-01-13 Institute for Oneworld Health Cftr inhibitor compounds and uses thereof
CN104447716A (zh) 2007-05-09 2015-03-25 沃泰克斯药物股份有限公司 Cftr调节剂
AU2008256937A1 (en) * 2007-05-25 2008-12-04 Vertex Pharmaceuticals Incorporated Ion channel modulators and methods of use
JP5389030B2 (ja) 2007-08-24 2014-01-15 バーテックス ファーマシューティカルズ インコーポレイテッド （特に）嚢胞性線維症の処置に有用なイソチアゾロピリジノン
SI2578571T1 (sl) 2007-11-16 2016-01-29 Vertex Pharmaceuticals Incorporated Izokinolinski modulatorji prenašalcev z atp-vezavno kaseto
EP3683218B1 (en) 2007-12-07 2024-09-18 Vertex Pharmaceuticals Incorporated Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid
CN101998854A (zh) * 2007-12-07 2011-03-30 沃泰克斯药物股份有限公司 3-(6-(1-(2,2-二氟苯并[d][1,3]间二氧杂环戊烯-5-基)环丙烷甲酰氨基)-3-甲基吡啶-2-基)苯甲酸的制剂
US20100036130A1 (en) 2007-12-07 2010-02-11 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
MX365732B (es) * 2007-12-07 2019-06-12 Vertex Pharma Procesos para producir acidos cicloalquilcarboxamido-piridin benzoicos.
EP2078711A1 (en) * 2007-12-28 2009-07-15 AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.p.A. (Aza)indole derivative substituted in position 5, pharmaceutical composition comprising it, intermediate compounds and preparation process therefor
NZ720282A (en) 2008-02-28 2017-12-22 Vertex Pharma Heteroaryl derivatives as cftr modulators
NZ616097A (en) 2008-03-31 2015-04-24 Vertex Pharma Pyridyl derivatives as cftr modulators
US8207205B2 (en) * 2008-04-21 2012-06-26 Institute For Oneworld Health Compounds, compositions and methods comprising oxadiazole derivatives
US20090264433A1 (en) * 2008-04-21 2009-10-22 Institute For Oneworld Health Compounds, Compositions and Methods Comprising Triazine Derivatives
WO2009131947A2 (en) * 2008-04-21 2009-10-29 Institute For Oneworld Health Compounds, compositions and methods comprising pyridazine derivatives
US8236838B2 (en) * 2008-04-21 2012-08-07 Institute For Oneworld Health Compounds, compositions and methods comprising isoxazole derivatives
AR072297A1 (es) 2008-06-27 2010-08-18 Novartis Ag Derivados de indol-2-il-piridin-3-ilo, composicion farmaceutica que los comprende y su uso en medicamentos para el tratamiento de enfermedades mediadas por la sintasa aldosterona.
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
US12458635B2 (en) 2008-08-13 2025-11-04 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
US20110237528A1 (en) * 2008-09-19 2011-09-29 Institute For Oneworld Health Compositions and methods comprising imidazole and triazole derivatives
AR073709A1 (es) 2008-09-29 2010-11-24 Vertex Pharma Unidades de dosis de acido 3-(6-(1-(2,2-difluorobenzeno (d) (1,3) dioxol-5-il) ciclopropancarboxamido)-3-metilpiridin-2-il) benzoico
EP2349263B1 (en) * 2008-10-23 2014-04-23 Vertex Pharmaceuticals Inc. Modulators of cystic fibrosis transmembrane conductance regulator
UA104876C2 (uk) * 2008-11-06 2014-03-25 Вертекс Фармасьютікалз Інкорпорейтед Модулятори atф-зв'язувальних касетних транспортерів
EP2940016A1 (en) * 2008-11-06 2015-11-04 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
PL2408750T3 (pl) 2009-03-20 2016-02-29 Vertex Pharma Sposób otrzymywania modulatorów błonowego regulatora przewodnictwa swoistego dla mukowiscydozy
US8511216B2 (en) * 2009-03-30 2013-08-20 Kanzaki Kokyukoki Mfg. Co., Ltd. Hydraulic actuator unit
US8343976B2 (en) * 2009-04-20 2013-01-01 Institute For Oneworld Health Compounds, compositions and methods comprising pyrazole derivatives
US8497271B2 (en) 2009-10-07 2013-07-30 Bristol-Myers Squibb Company Modulators of G protein-coupled receptor 88
US8426414B2 (en) 2009-10-09 2013-04-23 Bristol-Myers Squibb Company Modulators of G protein-coupled receptor 88
US8304577B2 (en) 2009-10-09 2012-11-06 Bristol-Myers Squibb Company Modulators of G protein-coupled receptor 88
MX2012004792A (es) 2009-10-22 2013-02-01 Vertex Pharma Composiciones para el tratamiento de fibrosis quistica y otras enfermedades cronicas.
US8802868B2 (en) 2010-03-25 2014-08-12 Vertex Pharmaceuticals Incorporated Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide
SI2826776T1 (sl) * 2010-03-25 2021-02-26 Vertex Pharmaceuticals Incorporated Trdna disperzija amorfne oblike (R)-1(2,2-difluorobenzo(D)(1,3)dioksol-5-il)-N-(1-(2,3-dihidroksipropil) -6-fluoro-2-(1-hidroksi-2-metilpropan-2-il)-1H-indol-5-il)- ciklopropankarboksamida
MX2012011655A (es) 2010-04-07 2012-11-23 Vertex Pharma Formas solidas de acido 3-(6-(1-(2,2-difluorobenzo [d][1-3]dioxol-5-il]ciclopropanocarboxamido)-3-metilpiridin-2-il) benzoico.
JP2013523833A (ja) 2010-04-07 2013-06-17 バーテックス ファーマシューティカルズ インコーポレイテッド ３−（６−（１−（２，２−ジフルオロベンゾ［ｄ］［１，３］ジオキソール−５−イル）シクロプロパンカルボキサミド）−３−メチルピリジン−２−イル）安息香酸の医薬組成物およびその投与
EP2560649A1 (en) * 2010-04-22 2013-02-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
MX353408B (es) * 2010-04-22 2018-01-11 Vertex Pharma Proceso para producir compuestos de cicloalquilcarboxamido-indol.
EP2560651A1 (en) 2010-04-22 2013-02-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
CA2796602A1 (en) 2010-04-22 2011-10-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
AU2011255237A1 (en) 2010-05-20 2012-11-29 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
US8563593B2 (en) 2010-06-08 2013-10-22 Vertex Pharmaceuticals Incorporated Formulations of (R)-1-(2,2-difluorobenzo[D] [1,3] dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide
WO2012027247A2 (en) * 2010-08-23 2012-03-01 Vertex Pharmaceuticals Incorporated Pharmaceutical composition of (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-n-(1-(2,3-dihydroxy propyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1h-indol-5-yl) cyclopropanecarboxamide and administration therof
CN102133402B (zh) * 2011-03-24 2013-06-12 首都医科大学附属北京同仁医院 囊性纤维化跨膜转导调节因子抑制剂在制备治疗糖尿病药物中的应用
EP2773349A1 (en) 2011-11-02 2014-09-10 Vertex Pharmaceuticals Incorporated Use of (n- [2, 4 -bis (1, 1 -dimethylethyl) - 5 - hydroxyphenyl]- 1, 4 - dihydro - 4 - oxoquinoline - 3 - carboxamide) for treating cftr mediated diseases
WO2013070961A1 (en) * 2011-11-08 2013-05-16 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
NZ727015A (en) 2012-01-25 2017-12-22 Vertex Pharma Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid
JP2015511583A (ja) 2012-02-27 2015-04-20 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ 薬学的組成物およびその投与
US8703953B2 (en) 2012-03-09 2014-04-22 Bristol-Myers Squibb Company Aryl ether-base kinase inhibitors
US8674108B2 (en) 2012-04-20 2014-03-18 Vertex Pharmaceuticals Incorporated Solid forms of N-[2,4-bis(1,1-dimethylethy)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
US9265772B2 (en) * 2012-05-11 2016-02-23 Reset Therapeutics, Inc. Carbazole-containing sulfonamides as cryptochrome modulators
AU2013270681A1 (en) 2012-06-08 2014-12-18 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for the treatment of CFTR -mediated disorders
AR092857A1 (es) 2012-07-16 2015-05-06 Vertex Pharma Composiciones farmaceuticas de (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-il)-n-(1-(2,3-dihidroxipropil)-6-fluoro-2-(1-hidroxi-2-metilpropan-2-il)-1h-indol-5-il)ciclopropancarboxamida y administracion de las mismas
US8901305B2 (en) 2012-07-31 2014-12-02 Bristol-Myers Squibb Company Aryl lactam kinase inhibitors
CN102816104B (zh) * 2012-08-30 2014-05-21 浙江大学 一种3-氰基吲哚类化合物的合成方法
ITMI20122065A1 (it) 2012-12-03 2014-06-04 Univ Padova Uso dei correttori del cftr nel trattamento delle patologie del muscolo striato
US9708337B2 (en) 2013-02-22 2017-07-18 Bristol-Myers Squibb Company Aryl amide-based kinase inhibitors
US10253027B2 (en) 2013-07-08 2019-04-09 Bristol-Myers Squibb Company Aryl lactam kinase inhibitors
AU2014349010C1 (en) 2013-11-12 2020-08-06 Vertex Pharmaceuticals Incorporated Process of preparing pharmaceutical compositions for the treatment of CFTR mediated diseases
TWI690521B (zh) 2014-04-07 2020-04-11 美商同步製藥公司 作為隱花色素調節劑之含有咔唑之醯胺類、胺基甲酸酯類及脲類
CN103922934B (zh) * 2014-04-11 2016-03-30 北京乐威泰克医药技术有限公司 活泼亚甲基化合物的烷基化方法
RU2744460C2 (ru) 2014-04-15 2021-03-09 Вертекс Фармасьютикалз Инкорпорейтед Фармацевтические композиции для лечения заболеваний, опосредованных муковисцидозным трансмембранным регулятором проводимости
MA41051B1 (fr) 2014-10-06 2020-11-30 Vertex Pharma Modulateurs du régulateur de conductance transmembranaire de la mucoviscidose
CN107250113B (zh) 2014-10-07 2019-03-29 弗特克斯药品有限公司 囊性纤维化跨膜传导调节蛋白的调节剂的共晶
DK3212189T3 (da) * 2014-10-31 2020-10-26 Abbvie Overseas Sarl Substituerede chromaner og fremgangsmåde til anvendelse deraf
RU2691136C2 (ru) 2014-11-18 2019-06-11 Вертекс Фармасьютикалз Инкорпорейтед Способ проведения высокопроизводительной тестовой высокоэффективной жидкостной хроматографии
EP3277647A1 (en) 2015-03-31 2018-02-07 Vertex Pharmaceuticals (Europe) Limited Deuterated vx-661
ES2740224T3 (es) 2015-04-10 2020-02-05 Bristol Myers Squibb Co 6H-isocromeno[3,4-c]piridinas y benzo[c][1,7]naftiridin-6-(5H)-onas como inhibidores de la cinasa asociada a adaptador 1 (AAK1)
CN105153105B (zh) * 2015-08-15 2018-01-19 浙江永宁药业股份有限公司 1‑(2,2‑二氟苯并[d][1,3]二氧杂环戊烯‑5‑基)环丙烷甲酸的合成方法及其中间体
CN109803962B (zh) 2016-09-30 2022-04-29 弗特克斯药品有限公司 囊性纤维化跨膜传导调控蛋白的调节剂、以及药物组合物
MD3551622T2 (ro) 2016-12-09 2021-03-31 Vertex Pharma Modulator al regulatorului conductanței transmembranare în fibroză chistică, compoziții farmaceutice, metode de tratament și procedeu pentru fabricarea modulatorului
US11253509B2 (en) 2017-06-08 2022-02-22 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
MA49631A (fr) 2017-07-17 2020-05-27 Vertex Pharma Méthodes de traitement de la fibrose kystique
JP7121794B2 (ja) 2017-08-02 2022-08-18 バーテックス ファーマシューティカルズ インコーポレイテッド ピロリジン化合物を調製するためのプロセス
WO2019079760A1 (en) 2017-10-19 2019-04-25 Vertex Pharmaceuticals Incorporated CRYSTALLINE FORMS AND COMPOSITIONS OF CFTR MODULATORS
CN111344287B (zh) 2017-11-14 2023-12-19 默沙东有限责任公司 作为吲哚胺2，3-双加氧酶(ido)抑制剂的新型取代的联芳基化合物
EP3709986B1 (en) 2017-11-14 2023-11-01 Merck Sharp & Dohme LLC Novel substituted biaryl compounds as indoleamine 2,3-dioxygenase (ido) inhibitors
EP3720849A2 (en) 2017-12-08 2020-10-14 Vertex Pharmaceuticals Incorporated Processes for making modulators of cystic fibrosis transmembrane conductance regulator
TWI810243B (zh) 2018-02-05 2023-08-01 美商維泰克斯製藥公司 用於治療囊腫纖化症之醫藥組合物
JP7214743B2 (ja) 2018-02-15 2023-01-30 バーテックス ファーマシューティカルズ インコーポレイテッド 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法
EP3774825A1 (en) 2018-04-13 2021-02-17 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
JP7640458B2 (ja) 2018-10-05 2025-03-05 アンナプルナ バイオ インコーポレイテッド Ａｐｊ受容体活性に関連する状態を処置するための化合物および組成物
CN109880090A (zh) * 2019-02-18 2019-06-14 华研(佛山)纳米材料有限公司 一种含石墨烯以及碳纳米管的聚酰亚胺导热材料、导热膜及其制备方法
UY38630A (es) 2019-04-03 2020-10-30 Vertex Pharma Agentes moduladores del regulador de la conductancia transmembrana de la fibrosis quística
WO2021030552A1 (en) 2019-08-14 2021-02-18 Vertex Pharmaceuticals Incorporated Crystalline forms of cftr modulators
TWI899097B (zh) 2019-08-14 2025-10-01 美商維泰克斯製藥公司 製備cftr調節劑之方法
TWI867024B (zh) 2019-08-14 2024-12-21 美商維泰克斯製藥公司 囊腫纖維化跨膜傳導調節蛋白之調節劑
CN113748716B (zh) * 2020-03-31 2022-10-28 华为技术有限公司 小区搜索的方法、装置及系统
CR20230120A (es) 2020-08-07 2023-09-01 Vertex Pharma Moduladores del regulador de la conductancia transmembrana de la fibrosis quística
IL300413A (en) 2020-08-13 2023-04-01 Vertex Pharma Crystal forms of CFTR modulators
WO2022040447A2 (en) 2020-08-20 2022-02-24 The Board Of Trustees Of The Leland Stanford Junior University Methods for treating respiratory diseases characterized by mucus hypersecretion
CN112851493B (zh) * 2020-11-10 2022-09-06 台州臻挚生物科技有限公司 一种2,4,5-三氟苯乙酸的制备方法
US12324802B2 (en) 2020-11-18 2025-06-10 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
KR20230118123A (ko) 2020-12-10 2023-08-10 버텍스 파마슈티칼스 인코포레이티드 낭성 섬유증 치료 방법
DE102021207925A1 (de) * 2021-07-23 2023-01-26 Continental Reifen Deutschland Gmbh Verbindung, Verfahren zu deren Herstellung sowie Verwendung der Verbindung als Alterungsschutzmittel und/oder Ozonschutzmittel und/oder Farbstoff
CA3267788A1 (en) 2022-09-15 2024-03-21 Idorsia Pharmaceuticals Ltd COMBINATION OF MACROCYCLIC CFTR MODULATORS WITH CFTR CORRECTORS AND/OR CFTR POTENTIALIZERS
WO2024056798A1 (en) 2022-09-15 2024-03-21 Idorsia Pharmaceuticals Ltd Macrocyclic cftr modulators
CN115872895A (zh) * 2023-02-22 2023-03-31 北京诺禾致源科技股份有限公司 用于衍生短链脂肪酸标准品作为内标的重标试剂及其制备方法、应用
WO2025186214A1 (en) 2024-03-05 2025-09-12 Idorsia Pharmaceuticals Ltd Macrocyclic cftr modulators
CN119219506A (zh) * 2024-10-12 2024-12-31 浙江博澳新材料股份有限公司 一种2-氯-4-硝基-6-溴-苯胺的合成方法

Family Cites Families (174)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5328173A (en) 1976-08-06 1978-03-16 Zenyaku Kogyo Kk Novel phenylmethanenitro compound and its preparation
US4138397A (en) 1978-02-27 1979-02-06 Richardson-Merrell Inc. 6-(2,3-Dihydro-5-benzofuranyl)acetamido penicillin derivatives
GB8524157D0 (en) * 1984-10-19 1985-11-06 Ici America Inc Heterocyclic amides
JPS61103861A (ja) 1984-10-27 1986-05-22 Nitto Kasei Kk アリ−ル置換シアン酢酸エステルの製造方法
US5304121A (en) 1990-12-28 1994-04-19 Boston Scientific Corporation Drug delivery system making use of a hydrogel polymer coating
GB9005014D0 (en) * 1990-03-06 1990-05-02 Janssen Pharmaceutica Nv N.(4.piperidinyl)(dihydrobenzofuran or dihydro.2h.benzopyran)carboxamide derivatives
US5886026A (en) 1993-07-19 1999-03-23 Angiotech Pharmaceuticals Inc. Anti-angiogenic compositions and methods of use
GB9317764D0 (en) 1993-08-26 1993-10-13 Pfizer Ltd Therapeutic compound
US5510379A (en) 1994-12-19 1996-04-23 Warner-Lambert Company Sulfonate ACAT inhibitors
US6099562A (en) 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
WO1998047868A1 (en) 1997-04-18 1998-10-29 Smithkline Beecham Plc Heterocycle-containing urea derivatives as 5ht1a, 5ht1b and 5ht1d receptor antagonists
TR199903148T2 (xx) 1997-06-21 2000-04-21 Roche Diagnostics Gmbh Antimetastatik ve antit�m�r etkinli�i olan barbit�rik asit t�revleri.
ATE364374T1 (de) 1997-08-11 2007-07-15 Pfizer Prod Inc Feste pharmazeutische dispersionen mit erhöhter bioverfügbarkeit
US20020017295A1 (en) 2000-07-07 2002-02-14 Weers Jeffry G. Phospholipid-based powders for inhalation
US6426331B1 (en) 1998-07-08 2002-07-30 Tularik Inc. Inhibitors of STAT function
EP1394150B1 (en) 1999-02-24 2011-01-19 F. Hoffmann-La Roche AG 4-Phenylpyridine derivatives and their use as NK-1 receptor antagonists
JP2003509429A (ja) 1999-09-10 2003-03-11 ノボ ノルディスク アクティーゼルスカブ タンパク質チロシンホスファターゼ（ｐｔｐアーゼ）のモジュレーター
IT1315267B1 (it) 1999-12-23 2003-02-03 Novuspharma Spa Derivati di 2-(1h-indol-3-il)-2-oxo-acetammidi ad attivita'antitumorale
TWI284639B (en) 2000-01-24 2007-08-01 Shionogi & Co A compound having thrombopoietin receptor agonistic effect
HUP0301493A2 (hu) * 2000-03-09 2003-08-28 Ono Pharmaceutical Co., Ltd. Indolszármazékok, eljárás előállításukra és alkalmazásuk
DE10038019A1 (de) 2000-08-04 2002-02-14 Bayer Ag Substituierte Triazolopyrid(az)ine
US6777400B2 (en) 2000-08-05 2004-08-17 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
US6562989B2 (en) 2000-08-07 2003-05-13 Yale University Catalyst for aromatic C—O, C—N, and C—C bond formation
TWI259180B (en) 2000-08-08 2006-08-01 Hoffmann La Roche 4-Phenyl-pyridine derivatives
AR030357A1 (es) 2000-08-18 2003-08-20 Lundbeck & Co As H Derivados 4 -, 5 -, 6 - y 7-indol
JP2005520171A (ja) 2001-04-10 2005-07-07 トランス　テック　ファーマ，インコーポレイテッド ドラッグディスカバリーに関する、プローブ、システム、および方法
CN1300116C (zh) 2001-04-16 2007-02-14 卫材株式会社 1h－吲唑化合物
SK287806B6 (sk) * 2001-06-28 2011-10-04 Pfizer Products Inc. Triamid-substituované indoly, benzofurány a benzotiofény ako inhibítory mikrozómového proteínu prenášajúceho triglyceridu (MTP) a/alebo sekrécie apolipoproteínu B (Apo B)
CA2448737C (en) 2001-07-20 2010-06-01 Boehringer Ingelheim (Canada) Ltd. Viral polymerase inhibitors
WO2003055482A1 (en) 2001-12-21 2003-07-10 Novo Nordisk A/S Amide derivatives as gk activators
US20060004010A1 (en) 2002-07-10 2006-01-05 Hiromu Habashita Ccr4 antagonist and medical use thereof
TWI244393B (en) 2002-08-06 2005-12-01 Idenix Pharmaceuticals Inc Crystalline and amorphous forms of beta-L-2'-deoxythymidine
US20060083784A1 (en) 2002-08-07 2006-04-20 Smithkline Beecham Corporation Amorphous pharmaceutical compositions
BR0314943A (pt) 2002-09-30 2005-08-02 Univ California Inibidores da proteìna reguladora da condutância transmembrana da fibrose cìstica e usos destes
JP2004131393A (ja) 2002-10-08 2004-04-30 Kowa Co 易溶出性製剤
JP4227389B2 (ja) * 2002-10-09 2009-02-18 浜松ホトニクス株式会社 撮像装置及びその製造方法
WO2004035571A1 (en) * 2002-10-15 2004-04-29 Rigel Pharmaceuticals, Inc. Substituted indoles and their use as hcv inhibitors
FR2846327B1 (fr) 2002-10-25 2006-03-24 Merck Sante Sas Derives de n-benzodioxolyl, n-benzodioxanyl et n-benzodioxepinyl arylcarboxamides utilisables dans le traitement de dyslipidemies et compositions pharmaceutiques les contenant.
EP1581217A4 (en) * 2002-11-01 2007-07-11 Merck & Co Inc CARBONYLAMINO-BENZIMIDAZOLE DERIVATIVES AS MODULATORS OF ANDROGENIC RECEPTORS
WO2004056744A1 (en) * 2002-12-23 2004-07-08 Janssen Pharmaceutica N.V. Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors
DE10306941A1 (de) 2003-02-18 2004-08-26 Merck Patent Gmbh Benzofuranoxyethylamine
US20050113423A1 (en) 2003-03-12 2005-05-26 Vangoor Frederick F. Modulators of ATP-binding cassette transporters
PL377633A1 (pl) 2003-04-03 2006-02-06 Merck Patent Gmbh Związki karbonylowe
EP4101846B1 (en) 2003-04-11 2023-08-02 PTC Therapeutics, Inc. 1,2,4-oxadiazole benzoic acid compounds and their use for nonsense suppression and the treatment of disease
US7696244B2 (en) 2003-05-16 2010-04-13 The Regents Of The University Of California Compounds having activity in increasing ion transport by mutant-CFTR and uses thereof
DE602004022819D1 (de) 2003-06-06 2009-10-08 Vertex Pharma Von atp-bindende kassette transportern
EP1638505B1 (en) 2003-06-27 2012-04-25 Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Amphiphilic pyridinium compounds, method of making and use thereof
NZ544935A (en) * 2003-08-15 2009-08-28 Lundbeck & Co As H Cyclopropyl derivatives as NK3 receptor antagonists
AR045368A1 (es) * 2003-08-15 2005-10-26 Lundbeck & Co As H Derivados de ciclopropilo como antagonistas del receptor nk3
RU2006111093A (ru) 2003-09-06 2007-10-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Модуляторы атр-связывающих кассетных транспортеров
US20050070718A1 (en) 2003-09-30 2005-03-31 Abbott Gmbh & Co. Kg Heteroaryl-substituted 1,3-dihydroindol-2-one derivatives and medicaments containing them
EP1680411A2 (en) 2003-10-08 2006-07-19 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters containing cycloalkyl or pyranyl groups
TW200522964A (en) 2003-10-16 2005-07-16 Sankyo Co 5-aryl-pyrimidine derivatives
JPWO2005040135A1 (ja) 2003-10-24 2007-03-08 小野薬品工業株式会社 抗ストレス薬およびその医薬用途
CN101675928A (zh) * 2003-11-14 2010-03-24 沃泰克斯药物股份有限公司 可用作atp-结合弹夹转运蛋白调控剂的噻唑和噁唑
GB0330043D0 (en) 2003-12-24 2004-01-28 Pharmacia Italia Spa Pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors process for their preparation and pharmaceutical compositions comprising them
US7977322B2 (en) 2004-08-20 2011-07-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
BRPI0507278A (pt) * 2004-01-30 2007-06-26 Vertex Pharma moduladores dos transportadores do cassete de ligação ao atp
EP2327724A3 (en) 2004-02-02 2011-07-27 Ambrx, Inc. Modified human growth hormone polypeptides and their uses
EP1740532A4 (en) 2004-03-30 2009-06-10 Univ California CFTR INHIBITOR COMPOUNDS CONTAINING HYDRAZIDS AND USES THEREOF
US20050222271A1 (en) 2004-03-31 2005-10-06 Le Huang Novel amorphous form of memantine hydrochloride
US20080138803A1 (en) 2004-06-01 2008-06-12 Galvan-Goldman Nee Galvan Barb Method of Detecting Cystic Fibrosis Associated Mutations
CA2569402A1 (en) 2004-06-04 2005-12-22 The Regents Of The University Of California Compounds having activity in increasing ion transport by mutant-cftr and uses thereof
US8354427B2 (en) 2004-06-24 2013-01-15 Vertex Pharmaceutical Incorporated Modulators of ATP-binding cassette transporters
RS56037B1 (sr) 2004-06-24 2017-09-29 Vertex Pharma Modulatori atp-vezujućih kasetnih transportera
US20140343098A1 (en) 2004-06-24 2014-11-20 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US20060000401A1 (en) 2004-07-01 2006-01-05 Massetti Joseph A Mooring line storage device
US8715727B2 (en) 2004-07-02 2014-05-06 Shionogi Inc. Tablet for pulsed delivery
MX2007001215A (es) 2004-08-06 2007-04-17 Otsuka Pharma Co Ltd Compuestos aromaticos.
DE102004047254A1 (de) 2004-09-29 2006-04-13 Merck Patent Gmbh Carbonylverbindungen
EP1799659A1 (en) 2004-10-13 2007-06-27 PTC Therapeutics, Inc. Compounds for nonsense suppression, and methods for their use
RU2416601C2 (ru) 2005-02-25 2011-04-20 Оно Фармасьютикал Ко., Лтд. Соединение индола и его применение
JP5385605B2 (ja) 2005-03-11 2014-01-08 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｐ結合カセットトランスポーターのモジュレーター
CA2600869A1 (en) 2005-03-18 2006-09-28 The Regents Of The University Of California Compounds having activity in correcting mutant-cftr processing and uses thereof
US7297700B2 (en) 2005-03-24 2007-11-20 Renovis, Inc. Bicycloheteroaryl compounds as P2X7 modulators and uses thereof
ES2398934T3 (es) 2005-03-28 2013-03-22 Toyama Chemical Co., Ltd. Proceso de la producción de1-(3-(2-(1-benzotiofen-5-il)etoxi)propil)acetidin-ol o sales del mismo
PL2402002T3 (pl) 2005-04-08 2018-11-30 Ptc Therapeutics, Inc. Kompozycje zawierające kwas 1,2,4-oksadiazolobenzoesowy i ich zastosowania do leczenia chorób związanych z przedwczesnym kodonem stop
JP5426878B2 (ja) * 2005-05-24 2014-02-26 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｐ−結合カセットトランスポーターのモジュレーター
US7999113B2 (en) * 2005-08-11 2011-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
ES2367844T3 (es) 2005-08-11 2011-11-10 Vertex Pharmaceuticals, Inc. Moduladores del regulador de la conductancia transmembrana de la fibrosis quística.
EP1926476B1 (en) 2005-08-29 2013-04-10 Sanofi-Aventis U.S. LLC Amorphous solid dispersions of 7-chloro-n,n,5-trimethyl-4-oxo-3-phenyl-3,5,-dihydro-4h-pyridazino[4,5-b]indole-1-acetamide
KR20080064971A (ko) 2005-10-06 2008-07-10 버텍스 파마슈티칼스 인코포레이티드 Ａｔｐ-결합 카세트 전달체의 조절자
US7401405B2 (en) * 2005-10-11 2008-07-22 Silverbrook Research Pty Ltd Method of fabricating inkjet nozzles having associated ink priming features
CN102775396B (zh) 2005-11-08 2014-10-08 沃泰克斯药物股份有限公司 Atp-结合弹夹转运蛋白的杂环调控剂
US20120232059A1 (en) 2005-11-08 2012-09-13 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette Transporters
HUE030390T2 (en) 2005-12-21 2017-05-29 Janssen Pharmaceutica Nv Triazolopyridazines as tyrosine kinase modulators
EP1979367A2 (en) 2005-12-24 2008-10-15 Vertex Pharmaceuticals Incorporated Quinolin-4-one derivatives as modulators of abc transporters
AU2006331565A1 (en) 2005-12-27 2007-07-05 Vertex Pharmaceuticals Incorporated Compounds useful in CFTR assays and methods therewith
EP3219705B1 (en) 2005-12-28 2020-03-11 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions of the amorphous form of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
US7671221B2 (en) 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
CA2856037C (en) 2005-12-28 2017-03-07 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US20070218138A1 (en) 2006-03-20 2007-09-20 Bittorf Kevin J Pharmaceutical Compositions
TWI428125B (zh) 2006-03-20 2014-03-01 Vertex Pharma 對包括vx-950之藥物實施噴霧乾燥之方法及由此方法製備之產物
EP2674428B1 (en) 2006-04-07 2016-04-06 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
US7645789B2 (en) 2006-04-07 2010-01-12 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
US10022352B2 (en) 2006-04-07 2018-07-17 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
CN101478964B (zh) * 2006-05-12 2012-02-29 沃泰克斯药物股份有限公司 N-[2,4-双(1,1-二甲基乙基)-5-羟苯基]-1,4-二氢-4-氧代喹啉-3-羧酰胺的组合物
CA2667453A1 (en) 2006-10-23 2008-05-02 Sgx Pharmaceuticals, Inc. Triazolo-pyridazine protein kinase modulators
NZ576642A (en) 2006-11-03 2011-11-25 Vertex Pharma Azaindole derivatives as cftr modulators
US8563573B2 (en) 2007-11-02 2013-10-22 Vertex Pharmaceuticals Incorporated Azaindole derivatives as CFTR modulators
US7754739B2 (en) * 2007-05-09 2010-07-13 Vertex Pharmaceuticals Incorporated Modulators of CFTR
WO2008064259A2 (en) 2006-11-21 2008-05-29 Biokey, Inc. Solid dispersion composition comprising fluvastatin
WO2008065732A1 (fr) 2006-11-27 2008-06-05 Nippon Polyurethane Industry Co., Ltd. Procédé de production d'un mélange à base d'isocyanate modifié contenant une liaison allophanate et une liaison isocyanurate
US20080260820A1 (en) 2007-04-19 2008-10-23 Gilles Borrelly Oral dosage formulations of protease-resistant polypeptides
CN104447716A (zh) 2007-05-09 2015-03-25 沃泰克斯药物股份有限公司 Cftr调节剂
JP5686596B2 (ja) * 2007-05-25 2015-03-18 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ 嚢胞性線維症膜貫通コンダクタンス制御因子の調節因子
US20110177999A1 (en) * 2007-08-09 2011-07-21 Vertex Pharmaceuticals Incorporated Therapeutic Combinations Useful in Treating CFTR Related Diseases
JP5389030B2 (ja) 2007-08-24 2014-01-15 バーテックス ファーマシューティカルズ インコーポレイテッド （特に）嚢胞性線維症の処置に有用なイソチアゾロピリジノン
EP2201010B1 (en) 2007-09-14 2013-11-06 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
NZ620027A (en) * 2007-09-14 2015-05-29 Vertex Pharma Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
SI2578571T1 (sl) 2007-11-16 2016-01-29 Vertex Pharmaceuticals Incorporated Izokinolinski modulatorji prenašalcev z atp-vezavno kaseto
TWI482768B (zh) 2007-11-22 2015-05-01 Zenyaku Kogyo Kk 雜環化合物之非晶質體、含有其之固體分散體、藥劑及其製法
CN101998854A (zh) * 2007-12-07 2011-03-30 沃泰克斯药物股份有限公司 3-(6-(1-(2,2-二氟苯并[d][1,3]间二氧杂环戊烯-5-基)环丙烷甲酰氨基)-3-甲基吡啶-2-基)苯甲酸的制剂
MX365732B (es) * 2007-12-07 2019-06-12 Vertex Pharma Procesos para producir acidos cicloalquilcarboxamido-piridin benzoicos.
EP3683218B1 (en) 2007-12-07 2024-09-18 Vertex Pharmaceuticals Incorporated Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid
US20100036130A1 (en) * 2007-12-07 2010-02-11 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
JP5637859B2 (ja) 2007-12-13 2014-12-10 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ 嚢胞性線維症膜コンダクタンスレギュレーターのモジュレーター
NZ720282A (en) * 2008-02-28 2017-12-22 Vertex Pharma Heteroaryl derivatives as cftr modulators
NZ616097A (en) * 2008-03-31 2015-04-24 Vertex Pharma Pyridyl derivatives as cftr modulators
CA2722371C (en) 2008-04-24 2016-06-21 Bristol-Myers Squibb Company Use of epothelone d in treating tau-associated diseases including alzheimer's disease
MX2011001782A (es) 2008-08-13 2012-02-08 Vertex Pharma Composicion farmaceutica y su administracion.
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
US20100256184A1 (en) 2008-08-13 2010-10-07 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
AR073709A1 (es) 2008-09-29 2010-11-24 Vertex Pharma Unidades de dosis de acido 3-(6-(1-(2,2-difluorobenzeno (d) (1,3) dioxol-5-il) ciclopropancarboxamido)-3-metilpiridin-2-il) benzoico
US20110257223A1 (en) * 2008-10-23 2011-10-20 Vertex Pharmaceuticals Incorporated Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
CN102224141B (zh) 2008-10-23 2014-10-08 沃泰克斯药物股份有限公司 N-(4-(7-氮杂双环[2.2.1]庚-7-基)-2-(三氟甲基)苯基)-4-氧代-5-(三氟甲基)-1,4-二氢喹啉-3-甲酰胺的固体形式
WO2010048564A1 (en) * 2008-10-23 2010-04-29 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
EP2349263B1 (en) * 2008-10-23 2014-04-23 Vertex Pharmaceuticals Inc. Modulators of cystic fibrosis transmembrane conductance regulator
UA104876C2 (uk) 2008-11-06 2014-03-25 Вертекс Фармасьютікалз Інкорпорейтед Модулятори atф-зв'язувальних касетних транспортерів
EP2940016A1 (en) 2008-11-06 2015-11-04 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
EP2382197B1 (en) 2008-12-30 2016-10-05 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
HRP20181261T1 (hr) 2009-03-20 2018-12-14 Vertex Pharmaceuticals Incorporated Modulatori regulatora transmembranske provodljivosti cistične fibroze
PL2408750T3 (pl) 2009-03-20 2016-02-29 Vertex Pharma Sposób otrzymywania modulatorów błonowego regulatora przewodnictwa swoistego dla mukowiscydozy
BR112012006031A2 (pt) * 2009-09-17 2019-09-24 Vertex Pharma processo para preparação de compostos azabicíclicos.
MX2012004792A (es) 2009-10-22 2013-02-01 Vertex Pharma Composiciones para el tratamiento de fibrosis quistica y otras enfermedades cronicas.
US8344147B2 (en) * 2009-10-23 2013-01-01 Vertex Pharmaceutical Incorporated Process for preparing modulators of cystic fibrosis transmembrane conductance regulator
CN102666546B (zh) * 2009-10-23 2015-09-09 沃泰克斯药物股份有限公司 N-(4-(7-氮杂双环[2.2.1]庚-7-基)-2-(三氟甲基)苯基)-4-氧代-5-(三氟甲基)-1,4-二氢喹啉-3-甲酰胺的固体形式
EP3037415A1 (en) * 2010-03-19 2016-06-29 Vertex Pharmaceuticals Inc. Solid form of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
US8802868B2 (en) * 2010-03-25 2014-08-12 Vertex Pharmaceuticals Incorporated Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide
SI2826776T1 (sl) * 2010-03-25 2021-02-26 Vertex Pharmaceuticals Incorporated Trdna disperzija amorfne oblike (R)-1(2,2-difluorobenzo(D)(1,3)dioksol-5-il)-N-(1-(2,3-dihidroksipropil) -6-fluoro-2-(1-hidroksi-2-metilpropan-2-il)-1H-indol-5-il)- ciklopropankarboksamida
JP2013523833A (ja) 2010-04-07 2013-06-17 バーテックス ファーマシューティカルズ インコーポレイテッド ３−（６−（１−（２，２−ジフルオロベンゾ［ｄ］［１，３］ジオキソール−５−イル）シクロプロパンカルボキサミド）−３−メチルピリジン−２−イル）安息香酸の医薬組成物およびその投与
MX2012011655A (es) 2010-04-07 2012-11-23 Vertex Pharma Formas solidas de acido 3-(6-(1-(2,2-difluorobenzo [d][1-3]dioxol-5-il]ciclopropanocarboxamido)-3-metilpiridin-2-il) benzoico.
EP2560651A1 (en) 2010-04-22 2013-02-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
MX353408B (es) 2010-04-22 2018-01-11 Vertex Pharma Proceso para producir compuestos de cicloalquilcarboxamido-indol.
CA2796602A1 (en) 2010-04-22 2011-10-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
EP2560649A1 (en) 2010-04-22 2013-02-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
EP2386606B1 (fr) 2010-04-30 2018-03-21 Total Marketing Services Utilisation de dérivés organogelateurs dans des compositions bitumineuses pour améliorer leur résistance aux agressions chimiques
AR081920A1 (es) 2010-05-20 2012-10-31 Vertex Pharma Procesos de produccion de moduladores del regulador de conductancia transmembrana de fibrosis quistica
AU2011255237A1 (en) * 2010-05-20 2012-11-29 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
US8563593B2 (en) * 2010-06-08 2013-10-22 Vertex Pharmaceuticals Incorporated Formulations of (R)-1-(2,2-difluorobenzo[D] [1,3] dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide
WO2012027247A2 (en) 2010-08-23 2012-03-01 Vertex Pharmaceuticals Incorporated Pharmaceutical composition of (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-n-(1-(2,3-dihydroxy propyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1h-indol-5-yl) cyclopropanecarboxamide and administration therof
CA2809263A1 (en) 2010-08-27 2012-03-01 Eleni Dokou Pharmaceutical composition and administrations thereof
US8802700B2 (en) 2010-12-10 2014-08-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
EP2773349A1 (en) 2011-11-02 2014-09-10 Vertex Pharmaceuticals Incorporated Use of (n- [2, 4 -bis (1, 1 -dimethylethyl) - 5 - hydroxyphenyl]- 1, 4 - dihydro - 4 - oxoquinoline - 3 - carboxamide) for treating cftr mediated diseases
WO2013070961A1 (en) 2011-11-08 2013-05-16 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US20140127901A1 (en) 2012-11-08 2014-05-08 Taiwan Semiconductor Manufacturing Company, Ltd. Low-k damage free integration scheme for copper interconnects
NZ727015A (en) 2012-01-25 2017-12-22 Vertex Pharma Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid
JP2015511583A (ja) 2012-02-27 2015-04-20 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ 薬学的組成物およびその投与
US8674108B2 (en) 2012-04-20 2014-03-18 Vertex Pharmaceuticals Incorporated Solid forms of N-[2,4-bis(1,1-dimethylethy)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
AU2013270681A1 (en) 2012-06-08 2014-12-18 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for the treatment of CFTR -mediated disorders
AR092857A1 (es) 2012-07-16 2015-05-06 Vertex Pharma Composiciones farmaceuticas de (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-il)-n-(1-(2,3-dihidroxipropil)-6-fluoro-2-(1-hidroxi-2-metilpropan-2-il)-1h-indol-5-il)ciclopropancarboxamida y administracion de las mismas
EP2914248B2 (en) 2012-11-02 2023-10-18 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for the treatment of cftr mediated diseases
US20140221424A1 (en) 2013-01-30 2014-08-07 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for use in the treatment of cystic fibrosis
AU2014302458A1 (en) 2013-06-26 2015-12-24 Proteostasis Therapeutics, Inc. Methods of modulating CFTR activity
AU2014349010C1 (en) 2013-11-12 2020-08-06 Vertex Pharmaceuticals Incorporated Process of preparing pharmaceutical compositions for the treatment of CFTR mediated diseases
AU2014370847B2 (en) 2013-12-27 2020-02-20 Chugai Seiyaku Kabushiki Kaisha Solid preparations containing tofogliflozin and process of producing the same
RU2744460C2 (ru) 2014-04-15 2021-03-09 Вертекс Фармасьютикалз Инкорпорейтед Фармацевтические композиции для лечения заболеваний, опосредованных муковисцидозным трансмембранным регулятором проводимости
MA41051B1 (fr) 2014-10-06 2020-11-30 Vertex Pharma Modulateurs du régulateur de conductance transmembranaire de la mucoviscidose
CN107250113B (zh) 2014-10-07 2019-03-29 弗特克斯药品有限公司 囊性纤维化跨膜传导调节蛋白的调节剂的共晶
RU2691136C2 (ru) 2014-11-18 2019-06-11 Вертекс Фармасьютикалз Инкорпорейтед Способ проведения высокопроизводительной тестовой высокоэффективной жидкостной хроматографии
MA41031A (fr) 2014-11-26 2017-10-03 Catabasis Pharmaceuticals Inc Conjugués cystéamine-acide gras et leur utilisation comme activateurs de l'autophagie
WO2016086136A1 (en) 2014-11-26 2016-06-02 Catabasis Pharmaceuticals, Inc. Fatty acid cysteamine conjugates of cftr modulators and their use in treating medical disorders
EP3277647A1 (en) 2015-03-31 2018-02-07 Vertex Pharmaceuticals (Europe) Limited Deuterated vx-661
WO2018183367A1 (en) 2017-03-28 2018-10-04 Van Goor Fredrick F Methods of treating cystic fibrosis in patients with residual function mutations

Also Published As

Publication number Publication date
ES2659364T3 (es) 2018-03-15
PT2674428T (pt) 2016-07-14
PT3091011T (pt) 2018-03-07
HUE026145T2 (en) 2016-05-30
PL2007756T3 (pl) 2016-01-29
CY1120045T1 (el) 2018-12-12
PL3327016T3 (pl) 2021-10-04
IN2014KN02423A (es) 2015-05-01
HUE027630T2 (en) 2016-10-28
JP5420395B2 (ja) 2014-02-19
US20240092766A1 (en) 2024-03-21
EP2007756A2 (en) 2008-12-31
EP2007756B1 (en) 2015-08-26
JP2014031384A (ja) 2014-02-20
US20160332997A1 (en) 2016-11-17
EP2674428A1 (en) 2013-12-18
ES2554353T3 (es) 2015-12-18
EP3091011B1 (en) 2017-12-27
CA2648719C (en) 2015-02-24
DK2674428T3 (en) 2016-04-18
CY1116979T1 (el) 2017-04-05
SI3327016T1 (sl) 2021-09-30
US20070244159A1 (en) 2007-10-18
DK2007756T3 (en) 2015-10-05
NZ596889A (en) 2013-06-28
CA2869945C (en) 2018-01-23
NZ611485A (en) 2014-09-26
BRPI0710965B1 (pt) 2020-08-18
SI2007756T1 (sl) 2015-11-30
EP3091011A1 (en) 2016-11-09
AU2007235260A1 (en) 2007-10-18
US9758510B2 (en) 2017-09-12
EP3882245A1 (en) 2021-09-22
US7776905B2 (en) 2010-08-17
US20220411410A1 (en) 2022-12-29
DK3091011T3 (en) 2018-02-26
ES2882684T3 (es) 2021-12-02
JP2009533351A (ja) 2009-09-17
EP3327016A1 (en) 2018-05-30
CN103254177A (zh) 2013-08-21
PL3091011T3 (pl) 2018-06-29
SI2674428T1 (sl) 2016-07-29
IL194576A0 (en) 2009-08-03
US10975061B2 (en) 2021-04-13
EP3327016B1 (en) 2021-06-16
CY1117731T1 (el) 2017-05-17
US20150119441A1 (en) 2015-04-30
MX2008012945A (es) 2009-01-15
WO2007117715A2 (en) 2007-10-18
BRPI0710965A2 (pt) 2012-01-31
HUE036165T2 (hu) 2018-06-28
LT3091011T (lt) 2018-04-10
IL194576A (en) 2016-12-29
CA2869945A1 (en) 2007-10-18
US20140057906A1 (en) 2014-02-27
PL2674428T3 (pl) 2017-01-31
NZ571803A (en) 2011-12-22
BRPI0710965B8 (pt) 2021-05-25
JP2015120762A (ja) 2015-07-02
CA2648719A1 (en) 2007-10-18
RU2008144124A (ru) 2010-05-20
US8912199B2 (en) 2014-12-16
EP2674428B1 (en) 2016-04-06
US11639347B2 (en) 2023-05-02
RU2451018C2 (ru) 2012-05-20
US10239867B2 (en) 2019-03-26
HUE055205T2 (hu) 2021-11-29
JP5827297B2 (ja) 2015-12-02
US8598181B2 (en) 2013-12-03
CN101460489A (zh) 2009-06-17
US20180162842A1 (en) 2018-06-14
PT2007756E (pt) 2015-11-02
US20200115366A1 (en) 2020-04-16
AU2007235260B2 (en) 2013-05-30
WO2007117715A3 (en) 2008-01-10
US20100331344A1 (en) 2010-12-30
ZA200809290B (en) 2009-10-28
SI3091011T1 (en) 2018-06-29

Similar Documents

Publication Publication Date Title
ES2580803T3 (es) Moduladores de transportadores del casete de unión a ATP
ES2594409T3 (es) Derivados de heteroarilo como moduladores del nAChR á7
ES2557465T3 (es) Moduladores de la actividad de HEC 1 y procedimientos para ello
ES2287120T3 (es) Nuevos compuestos biciclicos.
ES2502215T3 (es) Derivados de 2,3-dihidrobenzo[1,4]dioxin-2-ilmetilo como antagonistas de alfa2C para uso en el tratamiento de enfermedades del sistema nervioso central y periférico
Kwiecien et al. Recent Development on the Synthesis of Benzo [b]-and Naphtho [b] furans: A Review
AR105820A1 (es) Análogos de nucleósidos sustituidos en el anillo aromático bicíclico 6-6 para su uso como inhibidores de prmt5
AR079061A1 (es) Derivados del acido carbamoil-metil-amino-acetico sustituido como inhibidores de nep
AR062012A1 (es) Pirazoles como activadores de glucoquinasa
PE20050525A1 (es) Derivados de pirazol sustituido y compuestos relacionados como antagonistas del receptor de bradiquinina b1
AR060598A1 (es) Derivados de anilino-pirimidina inhibidores de proteinquinasas de la ruta nf-kb
PE20021006A1 (es) Derivados de 3-(4-amidopirrol-2-ilmetiliden)-2-indolinona como inhibidores de la proteinquinasa
AR076098A1 (es) Derivados de benzofurano
PE20110854A1 (es) DERIVADOS DE 1-FENIL-1H-PIRAZOLO[3,4-c]PIRIDINA-4-CARBONILAMINA COMO ANTAGONISTAS DE LOS RECEPTORES CCR1
PE20040913A1 (es) Enantiomeros (r) y (s) de derivados del acido tiofeno hidroxamico como inhibidores de desacetilasa histona (hdac)
AR082886A1 (es) Compuestos y composiciones farmaceuticas que los contienen
CO6150164A2 (es) Derivados de 2-metilmorfolina pirido-,pirazo-ypirimido-pirimidina como inhibidores de mtor
AR048669A1 (es) Derivados biciclicos de bisamida
AR069039A1 (es) Compuestos de diarilhidantoina, composicion farmaceutica, proceso de obtencion del compuesto, utiles para desordenes hiperproliferativos
CR20120361A (es) Compuestos divalentes y heterocíclicos unidos por puente oxa relacionados con nicotina y métodos de preparación de los mismos
AU2004287809A1 (en) Dihydrobenzofuranyl alkanamine derivatives as 5HT2c agonists
AR061369A1 (es) Derivados de pirimidina y composiciones farmaceuticas que los comprenden
PE20150877A1 (es) Composicion herbicida que tiene actividad herbicida mejorada
AR069607A1 (es) Inhibidores de la estearoil-coa desaturasa
AR057836A1 (es) Piperizinas como agentes contra la malaria