CA2931134C - Heteroaryl derivatives as cftr modulators - Google Patents

Heteroaryl derivatives as cftr modulators Download PDF

Info

Publication number
CA2931134C
CA2931134C CA2931134A CA2931134A CA2931134C CA 2931134 C CA2931134 C CA 2931134C CA 2931134 A CA2931134 A CA 2931134A CA 2931134 A CA2931134 A CA 2931134A CA 2931134 C CA2931134 C CA 2931134C
Authority
CA
Canada
Prior art keywords
compound
pharmaceutically acceptable
acceptable salt
disease
heteroaryl
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
CA2931134A
Other languages
English (en)
French (fr)
Other versions
CA2931134A1 (en
Inventor
Sara Hadida-Ruah
Mark Miller
Jinglan Zhou
Brian Bear
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
Priority to CA3039943A priority Critical patent/CA3039943C/en
Publication of CA2931134A1 publication Critical patent/CA2931134A1/en
Application granted granted Critical
Publication of CA2931134C publication Critical patent/CA2931134C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—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
    • A61K31/4965—Non-condensed pyrazines
    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • 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
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
    • 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
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A61P5/16—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4 for decreasing, blocking or antagonising the activity of the thyroid 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
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/20—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
    • 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
    • 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
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2570/00—Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cell Biology (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Obesity (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Psychology (AREA)
  • Rheumatology (AREA)
CA2931134A 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators Active CA2931134C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA3039943A CA3039943C (en) 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US3215908P 2008-02-28 2008-02-28
US61/032,159 2008-02-28
CA2716109A CA2716109C (en) 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CA2716109A Division CA2716109C (en) 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA3039943A Division CA3039943C (en) 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators

Publications (2)

Publication Number Publication Date
CA2931134A1 CA2931134A1 (en) 2009-09-03
CA2931134C true CA2931134C (en) 2019-07-30

Family

ID=40565305

Family Applications (3)

Application Number Title Priority Date Filing Date
CA2931134A Active CA2931134C (en) 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators
CA3039943A Active CA3039943C (en) 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators
CA2716109A Active CA2716109C (en) 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators

Family Applications After (2)

Application Number Title Priority Date Filing Date
CA3039943A Active CA3039943C (en) 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators
CA2716109A Active CA2716109C (en) 2008-02-28 2009-02-25 Heteroaryl derivatives as cftr modulators

Country Status (9)

Country Link
US (5) US8299099B2 (enExample)
EP (1) EP2271622B1 (enExample)
JP (3) JP5523352B2 (enExample)
CN (3) CN102245573B (enExample)
AU (1) AU2009219363B2 (enExample)
CA (3) CA2931134C (enExample)
ES (1) ES2647531T3 (enExample)
NZ (6) NZ703814A (enExample)
WO (1) WO2009108657A2 (enExample)

Families Citing this family (87)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1664006A2 (en) 2003-09-06 2006-06-07 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
DE602004022319D1 (de) * 2003-11-14 2009-09-10 Vertex Pharma Thiazole udn oxazole als modulatoren von atp-bindungs-kassetten-transportern
CN1938279B (zh) * 2004-01-30 2011-09-14 沃泰克斯药物股份有限公司 Atp-结合弹夹转运蛋白调控剂
US7977322B2 (en) 2004-08-20 2011-07-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
WO2006002421A2 (en) 2004-06-24 2006-01-05 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
EP1912983B1 (en) 2005-08-11 2011-06-08 Vertex Pharmaceuticals, Inc. Modulators of cystic fibrosis transmembrane conductance regulator
SI1945632T1 (sl) 2005-11-08 2014-03-31 Vertex Pharmaceuticals Incorporated Heterocikliäśni modulatorji za prenaĺ alce z atp-vezavno kaseto
CA2635760C (en) 2005-12-28 2014-07-15 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US7671221B2 (en) * 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
AU2006332726B2 (en) 2005-12-28 2012-12-13 Vertex Pharmaceuticals Incorporated. Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
US10022352B2 (en) 2006-04-07 2018-07-17 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
MX2008012945A (es) 2006-04-07 2009-01-15 Vertex Pharma Moduladores de transportadores de cartucho de union a adenosina-trifosfato celular (atp).
USRE50453E1 (en) 2006-04-07 2025-06-10 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
US8563573B2 (en) 2007-11-02 2013-10-22 Vertex Pharmaceuticals Incorporated Azaindole derivatives as CFTR modulators
NZ581259A (en) 2007-05-09 2012-07-27 Vertex Pharma Modulators of cystic fibrosis transmembrane conductance regulator
CA2687764A1 (en) * 2007-05-25 2008-12-04 Vertex Pharmaceuticals Incorporated Ion channel modulators and methods of use
EP2187884B1 (en) 2007-08-24 2016-03-30 Vertex Pharmaceuticals Incorporated Isothiazolopyridinones useful for the treatment of (inter alia) cystic fibrosis
US8551534B2 (en) * 2007-10-10 2013-10-08 Parion Sciences, Inc. Inhaled hypertonic saline delivered by a heated nasal cannula
PT2217572E (pt) 2007-11-16 2014-02-17 Vertex Pharma Moduladores de isoquinolina de transportadores de cassete de ligação a atp
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
SI2639224T1 (sl) 2007-12-07 2016-12-30 Vertex Pharmaceuticals Incorporated Postopek za pripravo cikloalkilkarboksiamido-piridinskih benzojskih kislin
AU2008333845C1 (en) 2007-12-07 2014-01-16 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
CN102245573B (zh) 2008-02-28 2013-11-20 沃泰克斯药物股份有限公司 作为cftr调节剂的杂芳基衍生物
WO2009123896A1 (en) 2008-03-31 2009-10-08 Vertex Pharmaceuticals Incorporated Pyridyl derivatives as cftr modulators
US12458635B2 (en) 2008-08-13 2025-11-04 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
RU2011117177A (ru) 2008-09-29 2012-11-10 Вертекс Фармасьютикалз Инкорпорейтед (Us) ДОЗИРОВАННЫЕ ЛЕКАРСТВЕННЫЕ ФОРМЫ 3-(6-(1-(2,2-ДИФТОРБЕНЗО[d][1,3]ДИОКСОЛ-5-ИЛ)ЦИКЛОПРОПАНКАРБОКСАМИДО)-3-МЕТИЛПИРИДИН-2-ИЛ)БЕНЗОЙНОЙ КИСЛОТЫ
CA2741718A1 (en) * 2008-10-23 2010-04-29 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US8513242B2 (en) 2008-12-12 2013-08-20 Cystic Fibrosis Foundation Therapeutics, Inc. Pyrimidine compounds and methods of making and using same
AU2010226400B2 (en) 2009-03-20 2016-07-14 Vertex Pharmaceuticals Incorporated Process for making modulators of cystic fibrosis transmembrane conductance regulator
WO2011008931A2 (en) * 2009-07-15 2011-01-20 Cystic Fibrosis Foundation Therapeutics, Inc. Arylpyrimidine compounds and combination therapy comprising same for treating cystic fibrosis & related disorders
MX2012007426A (es) * 2009-12-22 2012-07-23 Msd Oss Bv Derivados de amino-heteroarilo como bloqueadores de los canales activados por la hiperpolarizacion, controlados por nucleotidos ciclicos.
US8247436B2 (en) 2010-03-19 2012-08-21 Novartis Ag Pyridine and pyrazine derivative for the treatment of CF
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
ME02446B (me) 2010-04-07 2016-09-20 Vertex Pharma Čvrste forme 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioksol-5-il)ciklopropankarboksiamido)-3-metilpiridin-2-il)benzoeve kiseline
LT3150198T (lt) 2010-04-07 2021-12-10 Vertex Pharmaceuticals Incorporated 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioksol-5-il) ciklopropankarboksamido)-3-metilpiridin-2-il)benzoinės rūgšties farmacinė kompozicija ir jos įvedimas
MX342288B (es) 2010-04-22 2016-09-23 Vertex Pharma Proceso para producir compuestos de cicloalquilcarboxamido-indol.
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
US8334292B1 (en) 2010-06-14 2012-12-18 Cystic Fibrosis Foundation Therapeutics, Inc. Pyrimidine compounds and methods of making and using same
WO2012061926A1 (en) * 2010-11-08 2012-05-18 Zalicus Pharmaceuticals Ltd. Bisarylsulfone and dialkylarylsulfone compounds as calcium channel blockers
US8945605B2 (en) 2011-06-07 2015-02-03 Parion Sciences, Inc. Aerosol delivery systems, compositions and methods
AU2012267938B2 (en) 2011-06-07 2017-05-04 Parion Sciences, Inc. Methods of treatment
AR086745A1 (es) 2011-06-27 2014-01-22 Parion Sciences Inc 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida
EP2567959B1 (en) 2011-09-12 2014-04-16 Sanofi 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
US9056867B2 (en) 2011-09-16 2015-06-16 Novartis Ag N-substituted heterocyclyl carboxamides
CA2852991C (en) 2011-11-08 2019-12-31 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
CA2865519C (en) 2012-02-27 2018-01-02 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions comprising a solid dispersion of n-[2,4-bis(1,1-dimethylethyl0-5-hydroxyphenyl-1]-1,4-dihydro-4-oxoquinolone-3-carboxamide for treating cystic fibrosis
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
CA2872029A1 (en) 2012-05-29 2013-12-05 Parion Sciences, Inc. Dendrimer like amino amides possessing sodium channel blocker activity for the treatment of dry eye and other mucosal diseases
WO2013185112A1 (en) 2012-06-08 2013-12-12 Vertex Pharmaceuticals Incorporated Pharmaceuticl compositions for the treatment of cftr -mediated disorders
US9012496B2 (en) 2012-07-16 2015-04-21 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions 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 and administration thereof
US8729263B2 (en) 2012-08-13 2014-05-20 Novartis Ag 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions
ITMI20122065A1 (it) 2012-12-03 2014-06-04 Univ Padova Uso dei correttori del cftr nel trattamento delle patologie del muscolo striato
ES2674665T3 (es) 2012-12-17 2018-07-03 Parion Sciences, Inc. Compuestos de 3,5-diamino-6-cloro-N-(N-(4-fenilbutilo)carbamimidoilo)-pirazina-2-carboxamida
SI2931713T1 (sl) 2012-12-17 2017-03-31 Parion Sciences, Inc. Derivati kloro-pirazin karboksamida uporabni za zdravljenje bolezni favoriziranih z nezadostno hidracijo sluznice
AU2013363215B2 (en) 2012-12-17 2018-03-01 Parion Sciences, Inc. 3,5-diamino-6-chloro-N-(N-(4-phenylbutyl)carbamimidoyl) pyrazine-2- carboxamide compounds
MX2020011652A (es) * 2013-07-31 2022-09-27 Novartis Ag Derivados de piridazina 1,4-disustituida, y su uso para el tratamiento de afecciones relacionadas con la deficiencia de smn.
BR112016010403A2 (pt) 2013-11-12 2017-08-08 Vertex Pharma Processo de preparação de composições farmacêuticas para o tratamento de doenças mediadas por cftr
KR102447581B1 (ko) 2014-04-15 2022-09-28 버텍스 파마슈티칼스 인코포레이티드 낭포성 섬유증 막전도 조절자 매개 질환 치료용 약제학적 조성물
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
US9642831B2 (en) 2014-10-31 2017-05-09 Abbvie S.Á.R.L. Substituted chromanes and method of use
CA2968130C (en) 2014-11-18 2022-08-16 Vertex Pharmaceuticals Incorporated Process of conducting high throughput testing high performance liquid chromatography
CN105153106B (zh) * 2015-09-02 2017-08-25 阜新奥瑞凯新材料有限公司 一种2,2‑二氟胡椒酸甲酯的制备方法
EP3359144A1 (en) * 2015-10-09 2018-08-15 AbbVie S.À.R.L. Potentiator-corrector combinations useful in the treatment of cystic fibrosis
BR112018072047A2 (pt) * 2016-04-26 2019-02-12 AbbVie S.à.r.l. moduladores da proteína reguladora de condutância transmembranar de fibrose cística
MA46589A (fr) 2016-10-24 2019-08-28 Yumanity Therapeutics Inc Composés et utilisations de ces derniers
KR20190108118A (ko) 2017-01-06 2019-09-23 유마니티 테라퓨틱스, 인크. 신경계 장애의 치료를 위한 방법
US11873298B2 (en) 2017-10-24 2024-01-16 Janssen Pharmaceutica Nv Compounds and uses thereof
HRP20230030T1 (hr) 2018-02-15 2023-03-03 Vertex Pharmaceuticals Incorporated Makrocikli kao modulatori regulatora provodljivosti transmembrane cistične fibroze, njihovi farmaceutski pripravci, njihova uporaba u liječenju cistične fibroze, i postupak za njihovu proizvodnju
MX2020009942A (es) * 2018-03-23 2021-01-08 Yumanity Therapeutics Inc Compuestos y usos de los mismos.
AU2019334684B2 (en) 2018-09-09 2025-03-06 Qanatpharma Ag Use of CFTR modulators for treating cerebrovascular conditions
KR20220007845A (ko) 2019-01-24 2022-01-19 유마니티 테라퓨틱스, 인크. 화합물 및 이의 용도
AR118555A1 (es) 2019-04-03 2021-10-20 Vertex Pharma Agentes moduladores del regulador de la conductancia transmembrana de la fibrosis quística
CN114364675A (zh) 2019-05-05 2022-04-15 上海齐鲁锐格医药研发有限公司 Cdk抑制剂
CA3150162A1 (en) 2019-08-14 2021-02-18 Vertex Pharmaceuticals Incorporated Crystalline forms of cftr modulators
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
HUE066896T2 (hu) 2019-08-14 2024-09-28 Vertex Pharma Eljárás CFTR modulátorok elõállítására
EA202192047A1 (ru) 2019-11-13 2021-12-08 Юманити Терапьютикс, Инк. Соединения и их применение
CR20230120A (es) 2020-08-07 2023-09-01 Vertex Pharma Moduladores del regulador de la conductancia transmembrana de la fibrosis quística
US12324802B2 (en) 2020-11-18 2025-06-10 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
WO2022125826A1 (en) 2020-12-10 2022-06-16 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
WO2024072793A1 (en) * 2022-09-26 2024-04-04 Rectify Pharmaceuticals, Inc. Pyridine carboxamide compounds and their use in treating medical conditions
WO2024072794A1 (en) * 2022-09-26 2024-04-04 Rectify Pharmaceuticals, Inc. Pyridine carboxamide compounds and their use in treating medical conditions
KR20250110929A (ko) 2022-12-02 2025-07-21 뉴모라 테라퓨틱스, 인코포레이티드 신경학적 장애를 치료하는 방법
CN119285557A (zh) * 2024-10-11 2025-01-10 吉林大学 一种具有抗肿瘤活性的cd97和gsdme互作抑制剂及其应用

Family Cites Families (211)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3758475A (en) 1971-07-20 1973-09-11 Sandoz Ag Pyrido(2,3-d)pyrimidin 2 ones
EP0081756B1 (en) 1981-12-14 1985-05-15 MEDEA RESEARCH S.r.l. New compounds with antiinflammatory and antitussive activity, process for their preparation and relative pharmaceutical compositions
IT1226048B (it) 1981-12-14 1990-12-10 Medea Res Srl Composti ad attivita'antiinfiammatoria, processo per la loro preparazione e composizioni farmaceutiche relative
US4501729A (en) 1982-12-13 1985-02-26 Research Corporation Aerosolized amiloride treatment of retained pulmonary secretions
US5981714A (en) 1990-03-05 1999-11-09 Genzyme Corporation Antibodies specific for cystic fibrosis transmembrane conductance regulator and uses therefor
JP3167762B2 (ja) 1990-11-27 2001-05-21 武田薬品工業株式会社 ピリドピリダジン誘導体およびその用途
US5612360A (en) 1992-06-03 1997-03-18 Eli Lilly And Company Angiotensin II antagonists
CA2107196A1 (en) 1992-09-29 1994-03-30 Mitsubishi Chemical Corporation Carboxamide derivatives
GB9317764D0 (en) 1993-08-26 1993-10-13 Pfizer Ltd Therapeutic compound
KR100342275B1 (ko) 1993-10-21 2002-12-05 지.디. 썰 엘엘씨 산화질소신타제저해제로서유용한아미디노유도체
DE4405712A1 (de) 1994-02-23 1995-08-24 Basf Ag Substituierte Naphthyridine und deren Verwendung
CA2146701A1 (en) 1994-04-11 1995-10-12 Takashi Fujita Heterocyclic compounds having anti-diabetic activity, their preparation and their use
NZ293605A (en) 1994-09-27 1998-07-28 Janssen Pharmaceutica Nv N-substituted piperidinyl bicyclic benzoate derivatives, 3-alkoxy-4-hydroxy-piperidine intermediates, and pharmaceutical compositions
US5656256A (en) 1994-12-14 1997-08-12 The University Of North Carolina At Chapel Hill Methods of treating lung disease by an aerosol containing benzamil or phenamil
US5510379A (en) 1994-12-19 1996-04-23 Warner-Lambert Company Sulfonate ACAT inhibitors
WO1997036876A1 (en) 1996-04-03 1997-10-09 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
DE69713402T2 (de) 1996-08-23 2002-11-07 Agouron Pharma Liganden des neuropeptids y
JP2002511054A (ja) 1996-12-30 2002-04-09 メルク エンド カンパニー インコーポレーテッド ファルネシル蛋白トランスフェラーゼ阻害薬
US5948814A (en) 1997-02-20 1999-09-07 The Curators Of The University Of Missouri Genistein for the treatment of cystic fibrosis
WO1998047868A1 (en) 1997-04-18 1998-10-29 Smithkline Beecham Plc Heterocycle-containing urea derivatives as 5ht1a, 5ht1b and 5ht1d receptor antagonists
HUP0003881A3 (en) 1997-10-02 2001-04-28 Sankyo Co Amidocarboxylic acid derivatives
EP1054996B1 (en) 1998-02-17 2004-01-28 G.D. SEARLE & CO. Process for the enzymatic resolution of lactams
CN1311773A (zh) 1998-06-08 2001-09-05 先灵公司 神经肽y5受体拮抗剂
US6426331B1 (en) 1998-07-08 2002-07-30 Tularik Inc. Inhibitors of STAT function
AUPP609198A0 (en) 1998-09-22 1998-10-15 Curtin University Of Technology Use of non-peptidyl compounds for the treatment of insulin related ailments
NZ511394A (en) 1998-12-18 2003-07-25 Du Pont Pharm Co N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
PT1035115E (pt) 1999-02-24 2005-01-31 Hoffmann La Roche Derivados de 4-fenilpiridina e a sua utilizacao como antagonistas do receptor nk-1
CN1131212C (zh) 1999-02-24 2003-12-17 弗·哈夫曼-拉罗切有限公司 苯基－和吡啶基衍生物
PL350428A1 (en) 1999-02-24 2002-12-16 Hoffmann La Roche 3-phenylpyridine derivatives and their use as nk-1 receptor antagonists
UA71971C2 (en) 1999-06-04 2005-01-17 Agoron Pharmaceuticals Inc Diaminothiazoles, composition based thereon, a method for modulation of protein kinases activity, a method for the treatment of diseases mediated by protein kinases
WO2000078733A1 (de) 1999-06-18 2000-12-28 Bayer Aktiengesellschaft Phenoxyfluorpyrimidine
UA74539C2 (en) 1999-12-08 2006-01-16 Pharmacia Corp Crystalline polymorphous forms of celecoxib (variants), a method for the preparation thereof (variants), a pharmaceutical composition (variants)
WO2001046165A2 (en) 1999-12-16 2001-06-28 Novartis Ag N-heteroaryl-amides and their use as parasiticides
MXPA02006660A (es) 2000-01-07 2002-12-13 Transform Pharmaceuticals Inc Formacion, identificacion y analisis de diversas formas solidas de alto rendimiento.
AU2001233069A1 (en) 2000-01-28 2001-08-07 Biogen, Inc. Pharmaceutical compositions containing anti-beta 1 integrin compounds and uses
AU2001234689A1 (en) 2000-02-01 2001-08-14 Cor Therapeutics, Inc. Bivalent phenylene inhibitors of factor xa
US20010047100A1 (en) 2000-04-26 2001-11-29 Kjaersgaard Hans Joergen Chiral imidazoyl intermediates for the synthesis of 2-(4-imidazoyl)-cyclopropyl derivatives
AU2000249828A1 (en) 2000-05-03 2001-11-12 Taisho Pharmaceutical Co. Ltd. Stat4 and stat6 binding dipeptide derivatives
MXPA02000862A (es) 2000-06-01 2003-07-14 Bristol Myers Squibb Pharma Co Lactamas substituidas por succinatos ciclicos como inhibidores de la produccion de proteina abeta.
TWI259180B (en) 2000-08-08 2006-08-01 Hoffmann La Roche 4-Phenyl-pyridine derivatives
US6638926B2 (en) 2000-09-15 2003-10-28 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
JP4272338B2 (ja) 2000-09-22 2009-06-03 バイエル アクチェンゲゼルシャフト ピリジン誘導体
US20020115619A1 (en) 2000-10-04 2002-08-22 Rubenstein Ronald C. Compositions and methods for treatment of cystic fibrosis
GB2367816A (en) 2000-10-09 2002-04-17 Bayer Ag Urea- and thiourea-containing derivatives of beta-amino acids
EP1326854B1 (en) 2000-10-20 2004-06-23 MERCK PATENT GmbH Chiral binaphthol derivatives
US6884782B2 (en) 2000-11-08 2005-04-26 Amgen Inc. STAT modulators
EP1339402B1 (en) 2000-12-01 2010-08-25 Eisai Inc. Azaphenanthridone derivatives and their use as parp inhibitors
GB0102687D0 (en) 2001-02-02 2001-03-21 Pharmacia & Upjohn Spa Oxazolyl-pyrazole derivatives active as kinase inhibitors,process for their preparation and pharmaceutical compositions comprising them
US6531597B2 (en) 2001-02-13 2003-03-11 Hoffmann-La Roche Inc. Process for preparation of 2-phenyl acetic acid derivatives
EP1383799A4 (en) 2001-04-10 2008-08-06 Transtech Pharma Inc PROBES, SYSTEMS AND METHODS FOR DISCOVERING MEDICAMENTS
CN100398106C (zh) 2001-04-23 2008-07-02 弗·哈夫曼-拉罗切有限公司 Nk-1受体拮抗剂对抗良性前列腺增生的用途
AP2003002920A0 (en) 2001-05-22 2003-12-31 Neurogen Corp 5-substituted-2-arylpyridines as CRF1 modulators
US20030083345A1 (en) 2001-07-10 2003-05-01 Torsten Hoffmann Method of treatment and/or prevention of brain, spinal or nerve injury
US6627646B2 (en) 2001-07-17 2003-09-30 Sepracor Inc. Norastemizole polymorphs
WO2003007888A2 (en) 2001-07-20 2003-01-30 Adipogenix, Inc. Fat accumulation-modulating compounds
JP4558314B2 (ja) 2001-07-20 2010-10-06 ベーリンガー インゲルハイム （カナダ） リミテッド ウイルスポリメラーゼインヒビター
JP2005508904A (ja) 2001-09-11 2005-04-07 スミスクライン ビーチャム コーポレーション 血管新生阻害剤としてのフロ−及びチエノピリミジン誘導体
PA8557501A1 (es) 2001-11-12 2003-06-30 Pfizer Prod Inc Benzamida, heteroarilamida y amidas inversas
JP2003155285A (ja) 2001-11-19 2003-05-27 Toray Ind Inc 環状含窒素誘導体
JP2003221386A (ja) 2001-11-26 2003-08-05 Takeda Chem Ind Ltd 二環性誘導体、その製造法およびその用途
IL162620A0 (en) 2001-12-21 2005-11-20 Novo Nordisk As Amide derivatives as gk activators
TW200307539A (en) 2002-02-01 2003-12-16 Bristol Myers Squibb Co Cycloalkyl inhibitors of potassium channel function
TW200304820A (en) 2002-03-25 2003-10-16 Avanir Pharmaceuticals Use of benzimidazole analogs in the treatment of cell proliferation
TW200403058A (en) 2002-04-19 2004-03-01 Bristol Myers Squibb Co Heterocyclo inhibitors of potassium channel function
FR2840807B1 (fr) 2002-06-12 2005-03-11 Composition cosmetique de soin et/ou de maquillage, structuree par des polymeres silicones et des organogelateurs, sous forme rigide
GB0221443D0 (en) 2002-09-16 2002-10-23 Glaxo Group Ltd Pyridine derivates
JP2006505571A (ja) 2002-10-15 2006-02-16 リゲル ファーマシューテイカルズ、インコーポレイテッド 置換されたインドール及びｈｃｖ阻害剤としてのその使用
WO2004041163A2 (en) 2002-10-30 2004-05-21 Merck & Co., Inc. Piperidinyl cyclopentyl aryl benzylamide modulators of chemokine receptor activity
CA2508780A1 (en) 2002-12-12 2004-07-01 Pharmacia Corporation Method of using aminocyanopyridine compounds as mitogen activated protein kinase-activated protein kinase-2 inhibitors
EP1585739B1 (en) 2003-01-06 2011-04-20 Eli Lilly And Company Substituted arylcyclopropylacetamides as glucokinase activators
JP4675318B2 (ja) 2003-02-10 2011-04-20 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 Ｎ−アリールカルバミン酸エステルとハロ−ヘテロアリールとを反応させることによるｎ−ヘテロアリール−ｎ−アリール−アミンの調製のためのプロセスおよび類似のプロセス
WO2004080972A1 (en) * 2003-03-12 2004-09-23 Vertex Pharmaceuticals Incorporated Pirazole modulators of atp-binding cassette transporters
KR20060006953A (ko) 2003-04-30 2006-01-20 디 인스티튜트스 포 파마슈티컬 디스커버리, 엘엘씨 치환된 카르복실산
ATE440825T1 (de) * 2003-06-06 2009-09-15 Vertex Pharma Pyrimidin-derivate zur verwendung als modulatoren von atp-bindende kassette transportern
ES2386721T3 (es) 2003-06-27 2012-08-28 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Compuestos de piridinio anfifilos , método de fabricación y utilización de los mismos
GB0315111D0 (en) 2003-06-27 2003-07-30 Cancer Rec Tech Ltd Substituted 5-membered ring compounds and their use
JP2005053902A (ja) 2003-07-18 2005-03-03 Nippon Nohyaku Co Ltd フェニルピリジン類、その中間体及びこれを有効成分とする除草剤
JP2007504271A (ja) 2003-09-05 2007-03-01 ニューロジェン・コーポレーション Ｃｒｆ１受容体リガンドである、ヘテロアリール縮合ピリジン類、ピラジン類及びピリミジン類
EP1664006A2 (en) 2003-09-06 2006-06-07 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US7534894B2 (en) 2003-09-25 2009-05-19 Wyeth Biphenyloxy-acids
US20050070718A1 (en) 2003-09-30 2005-03-31 Abbott Gmbh & Co. Kg Heteroaryl-substituted 1,3-dihydroindol-2-one derivatives and medicaments containing them
WO2005035514A2 (en) 2003-10-08 2005-04-21 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters containing cycloalkyl or pyranyl groups
FR2861304B1 (fr) 2003-10-23 2008-07-18 Univ Grenoble 1 Modulateurs des canaux cftr
GB0325956D0 (en) 2003-11-06 2003-12-10 Addex Pharmaceuticals Sa Novel compounds
DE602004022319D1 (de) 2003-11-14 2009-09-10 Vertex Pharma Thiazole udn oxazole als modulatoren von atp-bindungs-kassetten-transportern
JP2007511572A (ja) 2003-11-19 2007-05-10 グラクソ　グループ　リミテッド 統合失調症治療のためのシクロオキシゲナーゼ−２選択的阻害剤の使用
US7977322B2 (en) * 2004-08-20 2011-07-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
CN1938279B (zh) * 2004-01-30 2011-09-14 沃泰克斯药物股份有限公司 Atp-结合弹夹转运蛋白调控剂
AU2005214225B2 (en) 2004-02-19 2010-05-20 Banyu Pharmaceutical Co., Ltd. Novel sulfone amide derivative
ES2241496B1 (es) 2004-04-15 2006-12-01 Almirall Prodesfarma, S.A. Nuevos derivados de piridina.
US20080015196A1 (en) 2004-04-16 2008-01-17 Neurogen Corporation Imidazopyrazines, Imidazopyridines, and Imidazopyrimidines as Crf1 Receptor Ligands
US7585885B2 (en) 2004-04-22 2009-09-08 Eli Lilly And Company Pyrrolidine derivatives useful as BACE inhibitors
US7618978B2 (en) 2004-04-22 2009-11-17 Eli Lilly And Company Amides as BACE inhibitors
US20080138803A1 (en) 2004-06-01 2008-06-12 Galvan-Goldman Nee Galvan Barb Method of Detecting Cystic Fibrosis Associated Mutations
US20140343098A1 (en) 2004-06-24 2014-11-20 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US8354427B2 (en) 2004-06-24 2013-01-15 Vertex Pharmaceutical Incorporated Modulators of ATP-binding cassette transporters
WO2006002421A2 (en) * 2004-06-24 2006-01-05 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
BRPI0512829A (pt) 2004-07-01 2008-04-08 Warner Lambert Co preparação de composições farmacêuticas contendo nanopartìculas
EP1771158A4 (en) 2004-07-02 2008-03-12 Advancis Pharmaceutical Corp TABLET FOR PULSE DISTRIBUTION
BRPI0514150A (pt) 2004-08-06 2007-11-27 Otsuka Pharma Co Ltd composto aromático ou um sal do mesmo, método para produzir o mesmo, e, composição farmacêutica para tratar a fibrose
AU2005289426A1 (en) 2004-09-27 2006-04-06 Amgen Inc. Substituted heterocyclic compounds and methods of use
WO2006040520A1 (en) 2004-10-12 2006-04-20 Astrazeneca Ab Quinazoline derivatives
EP1814888A1 (en) 2004-11-15 2007-08-08 Pfizer Products Incorporated Azabenzoxazoles for the treatment of cns disorders
BRPI0519326A2 (pt) 2004-12-15 2009-01-13 Dompe Pha R Ma Spa Res & Mfg derivados de Ácido 2-arilpropiânico e composiÇÕes farmacÊuticas contendo-os
JP4790260B2 (ja) 2004-12-22 2011-10-12 出光興産株式会社 アントラセン誘導体を用いた有機エレクトロルミネッセンス素子
JP2008528580A (ja) 2005-01-27 2008-07-31 アストラゼネカ・アクチエボラーグ Ｐ２ｘ７受容体の阻害剤である新規二環式芳香族化合物
US7888374B2 (en) 2005-01-28 2011-02-15 Abbott Laboratories Inhibitors of c-jun N-terminal kinases
JPWO2006082952A1 (ja) 2005-02-01 2008-06-26 武田薬品工業株式会社 アミド化合物
WO2006099256A2 (en) 2005-03-11 2006-09-21 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US7297700B2 (en) 2005-03-24 2007-11-20 Renovis, Inc. Bicycloheteroaryl compounds as P2X7 modulators and uses thereof
EP1710246A1 (en) 2005-04-08 2006-10-11 Schering Aktiengesellschaft Sulfoximine-pyrimidine Macrocycles and the salts thereof, a process for making them, and their pharmaceutical use against cancer
CA2606288A1 (en) 2005-04-18 2006-10-26 Neurogen Corporation Subtituted heteroaryl cb1 antagonists
KR20080000652A (ko) 2005-04-19 2008-01-02 바이엘 파마슈티칼스 코포레이션 아릴 알킬산 유도체 및 그의 용도
GB0510139D0 (en) 2005-05-18 2005-06-22 Addex Pharmaceuticals Sa Novel compounds B1
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
US8017635B2 (en) 2005-06-02 2011-09-13 Fmc Corporation Phenylalkyl substituted heteroaryl derivatives
WO2006136829A2 (en) 2005-06-21 2006-12-28 Astex Therapeutics Limited Pyrazole derivatives and their use as pka and pkb modulators
EP1912983B1 (en) 2005-08-11 2011-06-08 Vertex Pharmaceuticals, Inc. 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.
PT1928886E (pt) 2005-09-09 2011-07-14 Glaxosmithkline Llc Derivados de piridina e sua utilização para o tratamento de distúrbios psicóticos
DE602006011485D1 (de) 2005-09-23 2010-02-11 Hoffmann La Roche Neue dosierformulierung
CA2624683A1 (en) 2005-10-06 2007-04-19 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
DK1940821T3 (da) 2005-10-19 2013-06-10 Gruenenthal Gmbh Nye vanilloid-receptorligander og deres anvendelse til fremstilling af lægemidler.
WO2007054480A1 (en) 2005-11-08 2007-05-18 N.V. Organon 2-(benzimidazol-1-yl)-acetamide biaryl derivatives and their use as inhibitors of the trpv1 receptor
SI1945632T1 (sl) * 2005-11-08 2014-03-31 Vertex Pharmaceuticals Incorporated Heterocikliäśni modulatorji za prenaĺ alce z atp-vezavno kaseto
US20120232059A1 (en) 2005-11-08 2012-09-13 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette Transporters
WO2007067506A2 (en) 2005-12-05 2007-06-14 Smithkline Beecham Corporation 2-pyrimidinyl pyrazolopyridine erbb kinase inhibitors
US20090105272A1 (en) * 2005-12-24 2009-04-23 Grootenhuis Peter D J Prodrugs of modulators of ABC transporters
WO2007075946A1 (en) * 2005-12-27 2007-07-05 Vertex Pharmaceuticals Incorporated Compounds useful in cftr assays and methods therewith
CA2635760C (en) 2005-12-28 2014-07-15 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US7671221B2 (en) * 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
AU2006332726B2 (en) 2005-12-28 2012-12-13 Vertex Pharmaceuticals Incorporated. Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
US10022352B2 (en) 2006-04-07 2018-07-17 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
MX2008012945A (es) * 2006-04-07 2009-01-15 Vertex Pharma Moduladores de transportadores de cartucho de union a adenosina-trifosfato celular (atp).
US7645789B2 (en) * 2006-04-07 2010-01-12 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
CA2652072A1 (en) * 2006-05-12 2007-11-22 Vertex Pharmaceuticals Incorporated Compositions of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
US8563573B2 (en) 2007-11-02 2013-10-22 Vertex Pharmaceuticals Incorporated Azaindole derivatives as CFTR modulators
JP5284268B2 (ja) 2006-11-03 2013-09-11 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 Ｃｆｔｒモジュレーターとしてのアザインドール誘導体
US7754739B2 (en) * 2007-05-09 2010-07-13 Vertex Pharmaceuticals Incorporated Modulators of CFTR
AU2007327621A1 (en) 2006-11-27 2008-06-05 Novartis Ag Substituted dihydroimidazoles and their use in the treatment of tumors
US20080260820A1 (en) 2007-04-19 2008-10-23 Gilles Borrelly Oral dosage formulations of protease-resistant polypeptides
NZ581259A (en) 2007-05-09 2012-07-27 Vertex Pharma Modulators of cystic fibrosis transmembrane conductance regulator
EP2170901B1 (en) 2007-05-25 2015-07-01 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
WO2009023509A2 (en) 2007-08-09 2009-02-19 Vertex Pharmaceuticals Incorporated Therapeutic combinations useful in treating cftr related diseases
EP2187884B1 (en) * 2007-08-24 2016-03-30 Vertex Pharmaceuticals Incorporated Isothiazolopyridinones useful for the treatment of (inter alia) cystic fibrosis
DE102007042754A1 (de) 2007-09-07 2009-03-12 Bayer Healthcare Ag Substituierte 6-Phenylnikotinsäuren und ihre Verwendung
EP2222304A2 (en) 2007-09-14 2010-09-01 Vertex Pharmaceuticals Incorporated Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
AU2008298545B2 (en) 2007-09-14 2013-12-12 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US8118283B2 (en) 2007-09-21 2012-02-21 Lanny Vlasak Apparatus for aerating an aqueous solution
FR2921657A1 (fr) 2007-09-28 2009-04-03 Sanofi Aventis Sa Derives de nicotinamide, leur preparation et leur application en therapeutique
PT2217572E (pt) 2007-11-16 2014-02-17 Vertex Pharma Moduladores de isoquinolina de transportadores de cassete de ligação a atp
AU2008333845C1 (en) 2007-12-07 2014-01-16 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
SI2639224T1 (sl) 2007-12-07 2016-12-30 Vertex Pharmaceuticals Incorporated Postopek za pripravo cikloalkilkarboksiamido-piridinskih benzojskih kislin
US20100036130A1 (en) 2007-12-07 2010-02-11 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
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
AU2008335031B2 (en) * 2007-12-13 2013-11-28 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
CN102245573B (zh) 2008-02-28 2013-11-20 沃泰克斯药物股份有限公司 作为cftr调节剂的杂芳基衍生物
WO2009123896A1 (en) 2008-03-31 2009-10-08 Vertex Pharmaceuticals Incorporated Pyridyl derivatives as cftr modulators
US8784904B2 (en) 2008-04-10 2014-07-22 U.S. Nutraceuticals, LLC Plant derived seed extract rich in essential fatty acids derived from perilla seed: composition of matter, manufacturing process and use
GB0813709D0 (en) 2008-07-26 2008-09-03 Univ Dundee Method and product
KR20190143497A (ko) 2008-08-13 2019-12-30 버텍스 파마슈티칼스 인코포레이티드 제약 조성물 및 그의 투여
US20100256184A1 (en) 2008-08-13 2010-10-07 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
RU2011117177A (ru) 2008-09-29 2012-11-10 Вертекс Фармасьютикалз Инкорпорейтед (Us) ДОЗИРОВАННЫЕ ЛЕКАРСТВЕННЫЕ ФОРМЫ 3-(6-(1-(2,2-ДИФТОРБЕНЗО[d][1,3]ДИОКСОЛ-5-ИЛ)ЦИКЛОПРОПАНКАРБОКСАМИДО)-3-МЕТИЛПИРИДИН-2-ИЛ)БЕНЗОЙНОЙ КИСЛОТЫ
ES2532138T3 (es) 2008-10-23 2015-03-24 Vertex Pharmaceuticals Incorporated Moduladores del regulador de la conductancia transmembrana de la fibrosis quística
CA2741718A1 (en) * 2008-10-23 2010-04-29 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
RU2518479C2 (ru) 2008-10-23 2014-06-10 Вертекс Фармасьютикалз Инкорпорейтед Твердые формы n-(7-азабицикло[2.2.1]гептан-7-ил-)-2-(трифторметил)фенил)-4-оксо-5-(трифторметил)-1,4-дигидрохинолин-3-карбоксамида
US20110257223A1 (en) 2008-10-23 2011-10-20 Vertex Pharmaceuticals Incorporated Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
KR20160013251A (ko) 2008-11-06 2016-02-03 버텍스 파마슈티칼스 인코포레이티드 Ａｔｐ-결합 카세트 수송자의 조절자
UA104876C2 (uk) 2008-11-06 2014-03-25 Вертекс Фармасьютікалз Інкорпорейтед Модулятори atф-зв'язувальних касетних транспортерів
JP5699090B2 (ja) 2008-12-30 2015-04-08 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Ｖｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ 嚢胞性線維症膜コンダクタンス調節因子のモジュレーター
ES2683633T3 (es) 2009-03-20 2018-09-27 Vertex Pharmaceuticals Incorporated Moduladores de regulador de conductancia transmembrana de la fibrosis quística
AU2010226400B2 (en) 2009-03-20 2016-07-14 Vertex Pharmaceuticals Incorporated Process for making modulators of cystic fibrosis transmembrane conductance regulator
DK2427166T3 (da) 2009-05-07 2014-01-27 Gea Pharma Systems Ltd Tabletfremstillingsmodul og fremgangsmåde til kontinuerlig fremstilling af tabletter
WO2011035139A1 (en) 2009-09-17 2011-03-24 Vertex Pharmaceuticals Incorporated Process for preparing azabicyclic compounds
JP2013508414A (ja) * 2009-10-22 2013-03-07 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 嚢胞性線維症および他の慢性疾患の治療のための組成物
AU2010310617A1 (en) 2009-10-23 2012-05-24 Vertex Pharmaceuticals Incorporated Solid forms of N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide
JP5789611B2 (ja) 2009-10-23 2015-10-07 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制御因子のモジュレーターを調製するためのプロセス
CN103180298A (zh) 2010-03-19 2013-06-26 沃泰克斯药物股份有限公司 N-[2,4-双(1,1-二甲基乙基)-5-羟基苯基]-1,4-二氢-4-氧代喹啉-3-甲酰胺的固体形式
HRP20230661T1 (hr) 2010-03-25 2023-09-29 Vertex Pharmaceuticals Incorporated Sinteza i intermedijeri od (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
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
LT3150198T (lt) 2010-04-07 2021-12-10 Vertex Pharmaceuticals Incorporated 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioksol-5-il) ciklopropankarboksamido)-3-metilpiridin-2-il)benzoinės rūgšties farmacinė kompozicija ir jos įvedimas
ME02446B (me) 2010-04-07 2016-09-20 Vertex Pharma Čvrste forme 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioksol-5-il)ciklopropankarboksiamido)-3-metilpiridin-2-il)benzoeve kiseline
EP2560649A1 (en) 2010-04-22 2013-02-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
WO2011133953A1 (en) 2010-04-22 2011-10-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
MX342288B (es) 2010-04-22 2016-09-23 Vertex Pharma Proceso para producir compuestos de cicloalquilcarboxamido-indol.
AU2011242457A1 (en) 2010-04-22 2012-11-08 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
US20110288122A1 (en) 2010-05-20 2011-11-24 Vertex Pharmaceuticals Incorporated Pharmaceutical Compositions and Administrations Thereof
TW201202250A (en) * 2010-05-20 2012-01-16 Vertex Pharma Processes for producing modulators of cystic fibrosis transmembrane conductance regulator
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
NZ606805A (en) * 2010-08-23 2015-03-27 Vertex Pharma 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
EP2608775A2 (en) 2010-08-27 2013-07-03 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
US8802700B2 (en) 2010-12-10 2014-08-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
CA2853299A1 (en) 2011-11-02 2013-05-10 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
CA2852991C (en) 2011-11-08 2019-12-31 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
ES2742277T3 (es) 2012-01-25 2020-02-13 Vertex Pharma Composiciones farmacéuticas de ácido 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-ilo) ciclopropano carboxamido)-3metilpiridin-2-ilo)benzoico y su administración
CA2865519C (en) 2012-02-27 2018-01-02 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions comprising a solid dispersion of n-[2,4-bis(1,1-dimethylethyl0-5-hydroxyphenyl-1]-1,4-dihydro-4-oxoquinolone-3-carboxamide for treating cystic fibrosis
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
WO2013185112A1 (en) 2012-06-08 2013-12-12 Vertex Pharmaceuticals Incorporated Pharmaceuticl compositions for the treatment of cftr -mediated disorders
US9012496B2 (en) 2012-07-16 2015-04-21 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions 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 and administration thereof
HUE039864T2 (hu) 2012-11-02 2019-02-28 Vertex Pharma Gyógyászati készítmények CFTR-közvetítette betegségek kezelésére
US20140221424A1 (en) 2013-01-30 2014-08-07 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for use in the treatment of cystic fibrosis
KR102447581B1 (ko) 2014-04-15 2022-09-28 버텍스 파마슈티칼스 인코포레이티드 낭포성 섬유증 막전도 조절자 매개 질환 치료용 약제학적 조성물
SG10201902963PA (en) 2014-10-06 2019-05-30 Vertex Pharma Modulators of cystic fibrosis transmembrane conductance regulator
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
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
MA41031A (fr) 2014-11-26 2017-10-03 Catabasis Pharmaceuticals Inc Conjugués cystéamine-acide gras et leur utilisation comme activateurs de l'autophagie
CA2969587A1 (en) 2014-12-05 2016-06-09 Centre National De La Recherche Scientifique (Cnrs) Compounds for treating cystic fibrosis
JP6662885B2 (ja) 2015-01-26 2020-03-11 ライジェル ファーマシューティカルズ， インコーポレイテッド カルボン酸生物学的等価体としてのテトラゾロン
TWI730959B (zh) 2015-05-19 2021-06-21 英商葛蘭素史克智慧財產發展有限公司 作為激酶抑制劑之雜環醯胺

Also Published As

Publication number Publication date
US20150265612A1 (en) 2015-09-24
CN106432213A (zh) 2017-02-22
US9751890B2 (en) 2017-09-05
CA2716109A1 (en) 2009-09-03
US20130023538A1 (en) 2013-01-24
AU2009219363B2 (en) 2013-10-10
US8299099B2 (en) 2012-10-30
JP6035259B2 (ja) 2016-11-30
JP2014080440A (ja) 2014-05-08
NZ602030A (en) 2014-02-28
US20140371230A1 (en) 2014-12-18
CN103382201A (zh) 2013-11-06
NZ587545A (en) 2012-09-28
CA2716109C (en) 2016-07-19
US9504683B2 (en) 2016-11-29
CA3039943A1 (en) 2009-09-03
CN103382201B (zh) 2016-12-28
JP2015129193A (ja) 2015-07-16
JP2011513321A (ja) 2011-04-28
US20090221597A1 (en) 2009-09-03
US20170107225A1 (en) 2017-04-20
CA2931134A1 (en) 2009-09-03
ES2647531T3 (es) 2017-12-22
US8796312B2 (en) 2014-08-05
NZ703814A (en) 2016-06-24
NZ620944A (en) 2015-02-27
CA3039943C (en) 2021-07-13
NZ720282A (en) 2017-12-22
EP2271622B1 (en) 2017-10-04
JP5523352B2 (ja) 2014-06-18
CN102245573B (zh) 2013-11-20
CN102245573A (zh) 2011-11-16
HK1163661A1 (en) 2012-09-14
US9079916B2 (en) 2015-07-14
WO2009108657A2 (en) 2009-09-03
AU2009219363A1 (en) 2009-09-03
EP2271622A2 (en) 2011-01-12
WO2009108657A3 (en) 2009-12-03
NZ736561A (en) 2018-02-23

Similar Documents

Publication Publication Date Title
CA2931134C (en) Heteroaryl derivatives as cftr modulators
AU2007351454B2 (en) Azaindole derivatives as CFTR modulators
EP2271621B1 (en) Pyridyl derivatives as cftr modulators
US8563573B2 (en) Azaindole derivatives as CFTR modulators
AU2013205162B2 (en) Heteroaryl derivatives as CFTR modulators
AU2015228930B2 (en) Heteroaryl derivatives as CFTR modulators
AU2013231026B2 (en) Azaindole derivatives as CFTR modulators
HK1219729B (en) Pyridyl derivatives as cftr modulators

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20160526