ES2885181T3 - Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística - Google Patents

Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística Download PDF

Info

Publication number
ES2885181T3
ES2885181T3 ES18173500T ES18173500T ES2885181T3 ES 2885181 T3 ES2885181 T3 ES 2885181T3 ES 18173500 T ES18173500 T ES 18173500T ES 18173500 T ES18173500 T ES 18173500T ES 2885181 T3 ES2885181 T3 ES 2885181T3
Authority
ES
Spain
Prior art keywords
compound
spray
weight
agent
dried dispersion
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
ES18173500T
Other languages
English (en)
Spanish (es)
Inventor
Brian Dean Phenix
Laurent Jean-Claude Bagnol
Geoffrey Glen Brodeur
Sachin Chandran
Eleni Dokou
Lori Ann Ferris
Dragutin Knezic
Katie Lynn Mccarty
Ales Medek
Sara A Waggener
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=53175129&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ES2885181(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Vertex Pharmaceuticals Inc filed Critical Vertex Pharmaceuticals Inc
Application granted granted Critical
Publication of ES2885181T3 publication Critical patent/ES2885181T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines 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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with 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
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
    • 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
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pulmonology (AREA)
  • Inorganic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
ES18173500T 2014-04-15 2015-04-14 Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística Active ES2885181T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201461979848P 2014-04-15 2014-04-15
US201462059287P 2014-10-03 2014-10-03

Publications (1)

Publication Number Publication Date
ES2885181T3 true ES2885181T3 (es) 2021-12-13

Family

ID=53175129

Family Applications (3)

Application Number Title Priority Date Filing Date
ES18173500T Active ES2885181T3 (es) 2014-04-15 2015-04-14 Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística
ES15721912.2T Active ES2675858T3 (es) 2014-04-15 2015-04-14 Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística
ES21175519T Active ES2957761T3 (es) 2014-04-15 2015-04-14 Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística

Family Applications After (2)

Application Number Title Priority Date Filing Date
ES15721912.2T Active ES2675858T3 (es) 2014-04-15 2015-04-14 Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística
ES21175519T Active ES2957761T3 (es) 2014-04-15 2015-04-14 Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística

Country Status (28)

Country Link
US (3) US10206877B2 (enExample)
EP (4) EP3131582B1 (enExample)
JP (1) JP6543268B2 (enExample)
KR (1) KR102447581B1 (enExample)
CN (2) CN106163517B (enExample)
AU (2) AU2015247850B2 (enExample)
CA (1) CA2944140C (enExample)
CL (2) CL2016002600A1 (enExample)
CY (2) CY1120582T1 (enExample)
DK (3) DK3424534T3 (enExample)
ES (3) ES2885181T3 (enExample)
FI (1) FI3925607T3 (enExample)
HR (3) HRP20230709T1 (enExample)
HU (3) HUE055369T2 (enExample)
IL (3) IL266286B2 (enExample)
LT (3) LT3925607T (enExample)
MX (2) MX387720B (enExample)
PL (3) PL3424534T3 (enExample)
PT (3) PT3424534T (enExample)
RS (3) RS62140B1 (enExample)
RU (1) RU2744460C2 (enExample)
SG (2) SG11201607670XA (enExample)
SI (3) SI3131582T1 (enExample)
SM (3) SMT201800409T1 (enExample)
TR (1) TR201809684T4 (enExample)
UA (1) UA124567C2 (enExample)
WO (1) WO2015160787A1 (enExample)
ZA (1) ZA201606418B (enExample)

Families Citing this family (85)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7977322B2 (en) 2004-08-20 2011-07-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
ME02799B (me) 2004-06-24 2018-01-20 Vertex Pharma Modulatori ATP-vezujućih kasetnih transportera
SI1945632T1 (sl) 2005-11-08 2014-03-31 Vertex Pharmaceuticals Incorporated Heterocikliäśni modulatorji za prenaĺ alce z atp-vezavno kaseto
CA2635581C (en) 2005-12-28 2017-02-28 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
IN2014KN02423A (enExample) 2006-04-07 2015-05-01 Vertex Pharma
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
EP2164840A2 (en) 2007-05-09 2010-03-24 Vertex Pharmaceuticals Incorporated Modulators of cftr
CN101827593B (zh) 2007-08-24 2013-07-24 沃泰克斯药物股份有限公司 用于治疗(特别是)囊性纤维化的异噻唑并吡啶酮
WO2009064959A1 (en) 2007-11-16 2009-05-22 Vertex Pharmaceuticals Incorporated Isoquinoline modulators of atp-binding cassette transporters
PT2225230T (pt) 2007-12-07 2016-12-07 Vertex Pharma Formas sólidas de ácido 3-(6(1-(2,2-difluorobenzo[d][1,3] dioxol-5-il) ciclopropanocarboxamido)-3-metilpiridin-2-il) benzoico
PL2639223T3 (pl) 2007-12-07 2017-09-29 Vertex Pharmaceuticals Incorporated Sposób wytwarzania kwasów cykloalkilokarboksyamido-pirydyno-benzoesowych
NZ620944A (en) 2008-02-28 2015-02-27 Vertex Pharma Heteroaryl derivatives as cftr modulators
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
SI2408750T1 (sl) 2009-03-20 2015-11-30 Vertex Pharmaceuticals Incorporated Postopek za izdelavo modulatorjev cistično-fibroznega transmembranskega regulatorja prevodnosti
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
HRP20211752T1 (hr) 2010-04-07 2022-02-18 Vertex Pharmaceuticals Incorporated Farmaceutski pripravci 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioksol-5-il)ciklopropankarboksamido)-3-metilpiridin-2-il)benzojeve kiseline i njihova primjena
KR20130056244A (ko) 2010-04-22 2013-05-29 버텍스 파마슈티칼스 인코포레이티드 시클로알킬카르복스아미도-인돌 화합물의 제조 방법
HK1203840A1 (en) 2012-02-27 2015-11-06 沃泰克斯药物股份有限公司 Pharmaceutical composition and administration thereof
HK1209318A1 (en) 2012-07-16 2016-04-01 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions of (r)-1-(2,2-diflurorbenzo[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
KR102280372B1 (ko) 2013-11-12 2021-07-22 버텍스 파마슈티칼스 인코포레이티드 Cftr 매개된 질환 치료용 약제학적 조성물의 제조 방법
ES2885181T3 (es) 2014-04-15 2021-12-13 Vertex Pharma Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística
TN2017000083A1 (en) 2014-10-03 2018-07-04 Sanofi Sa Fused pentacyclic imidazole derivatives
WO2016057572A1 (en) 2014-10-06 2016-04-14 Mark Thomas Miller Modulators of cystic fibrosis transmembrane conductance regulator
JP6746569B2 (ja) 2014-10-07 2020-08-26 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Ｖｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ 嚢胞性線維症膜貫通コンダクタンス制御因子のモジュレーターの共結晶
DK3221692T3 (da) 2014-11-18 2021-08-23 Vertex Pharma Fremgangsmåde til udførsel af tests med høj kapacitet ved hjælp af højtryksvæskekromatografi
WO2016160945A1 (en) 2015-03-31 2016-10-06 Concert Pharmaceuticals, Inc. Deuterated vx-661
US10738030B2 (en) 2016-03-31 2020-08-11 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US10206915B2 (en) 2016-04-25 2019-02-19 Druggability Technologies Ip Holdco Limited Complexes of Ivacaftor and its salts and derivatives, process for the preparation thereof and pharmaceutical compositions containing them
HUP1600271A2 (hu) 2016-04-25 2017-10-30 Druggability Tech Ip Holdco Ltd Ivacaftor és Lumacaftor sóinak és származékainak komplexei, eljárás azok elõállítására és azok gyógyszerészetileg elfogadható készítményei
HUP1600270A2 (hu) 2016-04-25 2017-10-30 Druggability Tech Ip Holdco Ltd Ivacaftornak, sóinak és származékainak komplexei, eljárás azok elõállítására és azok gyógyszerészetileg elfogadott készítményei
US10383865B2 (en) 2016-04-25 2019-08-20 Druggability Technologies Ip Holdco Limited Pharmaceutical combination composition comprising complex formulations of Ivacaftor and Lumacaftor and their salts and derivatives, process for their preparation thereof and pharmaceutical compositions containing them
MA46357B1 (fr) 2016-09-30 2021-10-29 Vertex Pharma Modulateur de régulateur de conductance transmembranaire de fibrose kystique, compositions pharmaceutiques, procédés de traitement et procédé de fabrication du modulateur
CN110267948B (zh) 2016-12-09 2023-12-08 弗特克斯药品有限公司 囊性纤维化跨膜传导调控剂的调节剂、药物组合物、治疗方法和制备所述调节剂的方法
US20180280349A1 (en) 2017-03-28 2018-10-04 Vertex Pharmaceuticals Incorporated Methods of treating cystic fibrosis in patients with residual function mutations
MA54105A (fr) 2017-06-08 2021-09-15 Vertex Pharma Méthodes de traitement de la fibrose kystique
WO2019010092A1 (en) 2017-07-01 2019-01-10 Vertex Pharmaceuticals Incorporated COMPOSITIONS AND METHODS FOR TREATING CYSTIC FIBROSIS
CA3069225A1 (en) 2017-07-17 2019-01-24 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
CA3069226A1 (en) 2017-07-17 2019-01-24 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
MA49752A (fr) 2017-08-02 2021-04-21 Vertex Pharma Procédés de préparation de composés de pyrrolidine
TWI719349B (zh) 2017-10-19 2021-02-21 美商維泰克斯製藥公司 Ｃｆｔｒ調節劑之結晶形式及組合物
US20210228489A1 (en) * 2017-12-04 2021-07-29 Vertex Pharmaceuticals Incorporated Compositions for treating cystic fibrosis
KR102716244B1 (ko) 2017-12-08 2024-10-14 버텍스 파마슈티칼스 인코포레이티드 낭포성 섬유증 막횡단 전도 조절자의 조정제의 제조 방법
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
SI3752510T1 (sl) 2018-02-15 2023-03-31 Vertex Pharmaceuticals Incorporated Makrocikli kot modulatorji regulatorja transmembranske prevodnosti pri cistični fibrozi, farmacevtski sestavki iz le-teh, njihova uporaba pri zdravljenju cistične fibroze in postopek za njihovo proizvodnjo
US20210139514A1 (en) 2018-04-05 2021-05-13 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
WO2019200246A1 (en) 2018-04-13 2019-10-17 Alexander Russell Abela Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
CN110511204A (zh) * 2018-05-22 2019-11-29 上海特化医药科技有限公司 取代苯乙腈的制备方法
SMT202300102T1 (it) 2018-11-14 2023-05-12 Vertex Pharma Metodi di trattamento per la fibrosi cistica
CA3067611A1 (en) 2019-01-15 2020-07-15 Apotex Inc. Processes for the preparation of tezacaftor and intermediates thereof
TWI848092B (zh) 2019-04-03 2024-07-11 美商維泰克斯製藥公司 囊腫纖維化跨膜傳導調節蛋白調節劑
WO2020214921A1 (en) 2019-04-17 2020-10-22 Vertex Pharmaceuticals Incorporated Solid forms of modulators of cftr
WO2020242935A1 (en) 2019-05-29 2020-12-03 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
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
IL290408B2 (en) 2019-08-14 2025-10-01 Vertex Pharma Cystic fibrosis transmembrane conductance regulator modulators
MX2022001828A (es) 2019-08-14 2022-06-08 Vertex Pharma Formas cristalinas de moduladores del regulador de conductancia transmembrana de la fibrosis quistica (cftr).
HUE066896T2 (hu) 2019-08-14 2024-09-28 Vertex Pharma Eljárás CFTR modulátorok elõállítására
CR20230120A (es) 2020-08-07 2023-09-01 Vertex Pharma Moduladores del regulador de la conductancia transmembrana de la fibrosis quística
WO2022036060A1 (en) 2020-08-13 2022-02-17 Vertex Pharmaceuticals Incorporated Crystalline forms of cftr modulators
PE20231185A1 (es) 2020-10-07 2023-08-11 Vertex Pharma Moduladores del regulador de la conductancia transmembrana de la fibrosis quistica
US20230374038A1 (en) 2020-10-07 2023-11-23 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
EP4225737A1 (en) 2020-10-07 2023-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
MX2023004072A (es) 2020-10-07 2023-07-05 Vertex Pharma Moduladores del regulador de la conductancia transmembrana de la fibrosis quistica.
US20230416275A1 (en) 2020-10-07 2023-12-28 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
WO2022076621A1 (en) 2020-10-07 2022-04-14 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
EP4225750A1 (en) 2020-10-07 2023-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
JP2023545762A (ja) 2020-10-07 2023-10-31 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 嚢胞性線維症膜貫通コンダクタンス制御因子の調節因子
EP4225762A1 (en) 2020-10-07 2023-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
WO2022076627A1 (en) 2020-10-07 2022-04-14 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US12324802B2 (en) 2020-11-18 2025-06-10 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
MX2023006770A (es) 2020-12-10 2023-08-14 Vertex Pharma Metodos de tratamiento para fibrosis quistica.
TW202333699A (zh) 2022-02-03 2023-09-01 美商維泰克斯製藥公司 囊腫纖維化之治療方法
US20250320226A1 (en) 2022-02-03 2025-10-16 Vertex Pharmaceuticals Incorporated Methods of preparing and crystalline forms of (6a,12a)-17-amino-12-methyl-6,15-bis(trifluoromethyl)-13,19-dioxa-3,4,18-triazatricyclo[12.3.1.12,5]nonadeca-1(18),2,4,14,16-pentaen-6-ol
JP2025505643A (ja) 2022-02-08 2025-02-28 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調節因子
CN119343355A (zh) 2022-04-06 2025-01-21 弗特克斯药品有限公司 囊性纤维化跨膜传导调控因子的调节剂
AU2023272562A1 (en) 2022-05-16 2024-11-07 Vertex Pharmaceuticals Incorporated Solid forms of a macrocyclic compounds as cftr modulators and their preparation
CA3253026A1 (en) 2022-05-16 2023-11-23 Vertex Pharmaceuticals Incorporated TREATMENT METHODS FOR CYSTIC FIBROSIS
WO2024031081A1 (en) 2022-08-04 2024-02-08 Vertex Pharmaceuticals Incorporated Compositions for the treatment of cftr-mediated diseases
WO2025076240A1 (en) 2023-10-04 2025-04-10 Vertex Pharmaceuticals Incorporated Solid forms of modulators of cystic fibrosis transmembrane conductance regulator
WO2025076235A1 (en) 2023-10-04 2025-04-10 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
WO2025166342A1 (en) 2024-02-04 2025-08-07 Vertex Pharmaceuticals Incorporated Combination of vanzacaftor, tezacaftor, deutivacaftor for use in treating cystic fibrosis
WO2025171098A1 (en) 2024-02-07 2025-08-14 Vertex Pharmaceuticals Incorporated Compositions for the treatment of cftr-mediated diseases

Family Cites Families (335)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US206877A (en) * 1878-08-13 Improvement in paper-pulp washers
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
US5994341A (en) 1993-07-19 1999-11-30 Angiogenesis Technologies, Inc. Anti-angiogenic Compositions and methods for the treatment of arthritis
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
JPH10213820A (ja) 1997-01-31 1998-08-11 Canon Inc 液晶素子及び液晶装置
WO1998047868A1 (en) 1997-04-18 1998-10-29 Smithkline Beecham Plc Heterocycle-containing urea derivatives as 5ht1a, 5ht1b and 5ht1d receptor antagonists
BR9810450A (pt) 1997-06-21 2000-09-05 Roche Diagnostics Gmbh Derivados de ácido barbitúrico com atividade antimetastática e antitumor
EP0901786B1 (en) 1997-08-11 2007-06-13 Pfizer Products Inc. Solid pharmaceutical dispersions with enhanced bioavailability
US20020017295A1 (en) 2000-07-07 2002-02-14 Weers Jeffry G. Phospholipid-based powders for inhalation
DE69818094T2 (de) 1997-12-11 2004-07-08 Biochem Pharma Inc., Laval Antivirale verbindungen
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
SI1035115T1 (en) 1999-02-24 2005-02-28 F. Hoffmann-La Roche Ag 4-Phenylpyridine derivatives and their use as NK-1 receptor antagonists
AU6985200A (en) 1999-09-10 2001-04-17 Novo Nordisk A/S Modulators of protein tyrosine phosphatases (ptpases)
US7019026B1 (en) 1999-09-10 2006-03-28 Novo Nordisk A/S Modulators of Protein Tyrosine Phosphatases (PTPases)
AUPQ288499A0 (en) 1999-09-16 1999-10-07 Biota Scientific Management Pty Ltd Antiviral agents
US6514964B1 (en) 1999-09-27 2003-02-04 Amgen Inc. Fused cycloheptane and fused azacycloheptane compounds and their methods of use
IT1315267B1 (it) 1999-12-23 2003-02-03 Novuspharma Spa Derivati di 2-(1h-indol-3-il)-2-oxo-acetammidi ad attivita'antitumorale
WO2001052902A1 (en) 2000-01-24 2001-07-26 Isis Pharmaceuticals, Inc. Antisense modulation of inducible nitric oxide synthase expression
TWI284639B (en) 2000-01-24 2007-08-01 Shionogi & Co A compound having thrombopoietin receptor agonistic effect
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
KR100600550B1 (ko) 2000-10-20 2006-07-13 에자이 가부시키가이샤 질소 함유 방향환 유도체
EP1217000A1 (en) 2000-12-23 2002-06-26 Aventis Pharma Deutschland GmbH Inhibitors of factor Xa and factor VIIa
GB0102109D0 (en) 2001-01-26 2001-03-14 Syngenta Ltd Chemical process
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
DE60228447D1 (de) 2001-06-28 2008-10-02 Pfizer Prod Inc Triamidsubstituierte indole, benzofurane und benzothiophene als inhibitoren des mikrosomalen triglyceridtransferproteins (mtp) und/oder der sekretion von apolipoprotein b (apo b)
CA2448737C (en) 2001-07-20 2010-06-01 Boehringer Ingelheim (Canada) Ltd. Viral polymerase inhibitors
AUPR738301A0 (en) 2001-08-30 2001-09-20 Starpharma Limited Chemotherapeutic agents
EP1446115B1 (en) 2001-11-13 2008-02-27 Merck Frosst Canada Ltd. Cyanoalkylamino derivatives as protease inhibitors
CA2465597A1 (en) 2001-11-14 2003-06-12 Ben Zion Dolitzky Amorphous and crystalline forms of losartan potassium and process for their preparation
WO2003055482A1 (en) 2001-12-21 2003-07-10 Novo Nordisk A/S Amide derivatives as gk activators
US7074805B2 (en) 2002-02-20 2006-07-11 Abbott Laboratories Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
US20030158188A1 (en) 2002-02-20 2003-08-21 Chih-Hung Lee Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
AU2003228744A1 (en) 2002-04-29 2003-11-17 The Ohio State University Inhibition of protein tyrosine phosphatases and sh2 domains by a neutral phosphotyrosine mimetic
PL215132B1 (pl) 2002-06-27 2013-10-31 Novo Nordisk As Pochodna arylokarbonylowa jako srodek terapeutyczny, jej zastosowanie i kompozycja farmaceutyczna ja zawierajaca
JPWO2004007472A1 (ja) 2002-07-10 2005-11-17 小野薬品工業株式会社 Ｃｃｒ４アンタゴニストおよびその医薬用途
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
KR20050057408A (ko) 2002-09-18 2005-06-16 오노 야꾸힝 고교 가부시키가이샤 트리아자스피로[5.5]운데칸 유도체 및 이를 유효 성분으로하는 약제
CN100356922C (zh) 2002-09-30 2007-12-26 加利福尼亚大学董事会 囊性纤维化跨膜传导调节因子蛋白抑制剂及其用途
JP2004131393A (ja) 2002-10-08 2004-04-30 Kowa Co 易溶出性製剤
CA2501547A1 (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.
WO2004041277A1 (en) 2002-11-01 2004-05-21 Merck & Co., Inc. Carbonylamino-benzimidazole derivatives as androgen receptor modulators
DE10251019A1 (de) 2002-11-02 2004-05-19 Aventis Pharma Deutschland Gmbh Neue Pyrimidin-4,6-dicarbonsäurediamide zur selektiven Inhibierung von Kollagenasen
ATE388941T1 (de) 2002-11-02 2008-03-15 Sanofi Aventis Deutschland Neue pyrimidin-4,6-dicarbons urediamide zur selektiven inhibierung von kollagenasen
US20040146941A1 (en) 2002-11-04 2004-07-29 Biliang Zhang Chemical encoding technology for combinatorial synthesis
WO2004056744A1 (en) 2002-12-23 2004-07-08 Janssen Pharmaceutica N.V. Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors
DE10300017A1 (de) 2003-01-03 2004-07-15 Aventis Pharma Deutschland Gmbh Selektive MMP 13 Inhibitoren
SG2012000667A (en) 2003-01-08 2015-03-30 Univ Washington Antibacterial agents
US6933311B2 (en) 2003-02-11 2005-08-23 Abbott Laboratories Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
JP4909068B2 (ja) 2003-02-14 2012-04-04 グラクソ グループ リミテッド カルボキサミド誘導体
DE10306941A1 (de) 2003-02-18 2004-08-26 Merck Patent Gmbh Benzofuranoxyethylamine
EP1601657A1 (en) 2003-03-12 2005-12-07 Vertex Pharmaceuticals Incorporated Pyrazole modulators of atp-binding cassette transporters
NZ543366A (en) 2003-04-03 2008-11-28 Merck Patent Gmbh Carbonyl compounds
US20050164951A1 (en) 2003-04-03 2005-07-28 The Regents Of The University Of California Inhibitors for the soluble epoxide hydrolase
DE10315377A1 (de) 2003-04-03 2004-10-14 Merck Patent Gmbh Carbonylverbindungen
EP3889142B1 (en) 2003-04-11 2022-06-15 PTC Therapeutics, Inc. 1,2,4-oxadiazole benzoic acid compounds and their use for nonsense suppression and the treatment of disease
ATE482747T1 (de) 2003-04-11 2010-10-15 High Point Pharmaceuticals Llc Neue amide derivate und deren pharmazeutische verwendungen
WO2004110352A2 (en) 2003-05-16 2004-12-23 The Regents Of The University Of California Compounds having activity in increasing ion transport by mutant-cftr and uses thereof
WO2004111014A1 (en) 2003-06-06 2004-12-23 Vertex Pharmaceuticals Incorporated Pyrimidine derivatives as modulators of atp-binding cassette transporters
WO2005002519A2 (en) 2003-06-27 2005-01-13 Henry M.Jackson Foundation For The Advancement Of Military Medicine, Inc. Amphiphilic pyridinium compounds, method of making and use thereof
US20050113576A1 (en) 2003-08-05 2005-05-26 Chih-Hung Lee Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
NZ544935A (en) 2003-08-15 2009-08-28 Lundbeck & Co As H Cyclopropyl derivatives as NK3 receptor antagonists
MXPA06002567A (es) 2003-09-06 2006-09-04 Vertex Pharma Moduladores de transportadores con casete de union de atp.
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
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
CN1925854A (zh) 2003-11-14 2007-03-07 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
ES2791303T3 (es) 2004-01-30 2020-11-03 Vertex Pharma Compuesto intermedio de moduladores de transportadores de casete de unión a ATP
BRPI0507169A (pt) 2004-02-02 2007-06-26 Ambrx Inc polipeptìdeos do hormÈnio de crescimento humano modificados e seu usos
CN1960966A (zh) 2004-03-30 2007-05-09 加利福尼亚大学董事会 含酰肼cftr抑制剂化合物及其用途
US20050222271A1 (en) 2004-03-31 2005-10-06 Le Huang Novel amorphous form of memantine hydrochloride
FR2868417B1 (fr) 2004-04-02 2006-06-23 Rhodia Chimie Sa Procede de formation d'une liaison carbone-carbone
AU2005249154B2 (en) 2004-06-01 2011-02-10 Luminex Molecular Diagnostics, Inc. Method of detecting cystic fibrosis associated mutations
US7939558B2 (en) 2004-06-04 2011-05-10 The Regents Of The University Of California Compounds having activity in increasing ion transport by mutant-CFTR and uses thereof
US20140343098A1 (en) 2004-06-24 2014-11-20 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
ME02799B (me) 2004-06-24 2018-01-20 Vertex Pharma Modulatori ATP-vezujućih kasetnih transportera
US8354427B2 (en) 2004-06-24 2013-01-15 Vertex Pharmaceutical Incorporated Modulators of ATP-binding cassette transporters
CA2572292A1 (en) 2004-07-02 2006-02-09 Advancis Pharmaceutical Corporation Tablet for pulsed delivery
GB0416730D0 (en) 2004-07-27 2004-09-01 Novartis Ag Organic compounds
AU2005268030B2 (en) 2004-08-06 2009-02-19 Otsuka Pharmaceutical Co., Ltd. Aromatic compounds
DE102004047254A1 (de) 2004-09-29 2006-04-13 Merck Patent Gmbh Carbonylverbindungen
KR20070067165A (ko) 2004-10-13 2007-06-27 피티씨 테라퓨틱스, 인크. 넌센스 변이 억제용 화합물, 및 이의 사용 방법
CN101084216B (zh) 2004-10-20 2011-09-14 加利福尼亚大学董事会 可溶性环氧化物水解酶的改进抑制剂
WO2006057448A1 (ja) 2004-11-26 2006-06-01 Takeda Pharmaceutical Company Limited アリールアルカン酸誘導体
EP1676834A1 (en) * 2004-12-30 2006-07-05 Sanofi-Aventis Deutschland GmbH Fused bicyclic carboxamide derivates for use as CXCR2 inhibitors in the treatment of inflammation
MX2007010112A (es) 2005-02-25 2007-10-12 Ono Pharmaceutical Co Compuesto indol y uso del mismo.
WO2006099256A2 (en) 2005-03-11 2006-09-21 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
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
GB0506133D0 (en) 2005-03-24 2005-05-04 Sterix Ltd Compound
US20100120789A1 (en) 2005-03-24 2010-05-13 Nigel Vicker Compound
CN101151257B (zh) 2005-03-28 2012-07-18 富山化学工业株式会社 生产1-（3-（2-（1-苯并噻吩-5-基）乙氧基）丙基）氮杂环丁-3-醇或其盐的方法
JP2006282534A (ja) 2005-03-31 2006-10-19 Fuji Photo Film Co Ltd アミド類の製造方法
CA2603402C (en) 2005-04-08 2017-10-31 Ptc Therapeutics, Inc. Compositions of an orally active 1,2,4-oxadiazole for nonsense mutation suppression therapy
JP2008537953A (ja) 2005-04-15 2008-10-02 エラン ファーマシューティカルズ，インコーポレイテッド ブラジキニンｂ１受容体拮抗作用に有用な新規化合物
WO2006127588A2 (en) 2005-05-24 2006-11-30 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
WO2007021982A2 (en) 2005-08-11 2007-02-22 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
ZA200802172B (en) 2005-08-11 2009-06-24 Vertex Pharma Modulators of cystic fibrosis transmembrane conductance regulator
ME01560B (me) 2005-08-29 2014-04-20 Sanofi Aventis Us Llc Amorfna čvrsta disperzija 7-hlor-n,n,5-trimetil-4-okso-3-fenil-3,5,-dihidr0-4h-piridazino[4,5-b]indol-1-acetamida
KR20080064971A (ko) 2005-10-06 2008-07-10 버텍스 파마슈티칼스 인코포레이티드 Ａｔｐ-결합 카세트 전달체의 조절자
EP1942732A2 (en) 2005-11-02 2008-07-16 Cytokinetics, Inc. Certain chemical entities, compositions, and methods
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
GB0525144D0 (en) 2005-12-09 2006-01-18 Novartis Ag Organic compounds
ES2612377T3 (es) 2005-12-21 2017-05-16 Janssen Pharmaceutica N.V. Triazolopiridazinas como moduladores de tirosina cinasas
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
CA2635581C (en) 2005-12-28 2017-02-28 Vertex Pharmaceuticals Incorporated Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
CN101395147B (zh) 2005-12-28 2013-05-29 弗特克斯药品有限公司 作为atp-结合盒转运蛋白调节剂用于治疗囊性纤维化的1-(苯并[d][1,3]间二氧杂环戊烯-5-基)-n-(苯基)环丙烷-甲酰胺衍生物及相关化合物
US7671221B2 (en) 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
AR059826A1 (es) 2006-03-13 2008-04-30 Univ California Inhibidores de urea conformacionalmente restringidos de epoxido hidrolasa soluble
US20070218012A1 (en) 2006-03-20 2007-09-20 Bittorf Kevin J Pharmaceutical Compositions
AU2007226983A1 (en) 2006-03-20 2007-09-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions
AU2007230991A1 (en) 2006-03-22 2007-10-04 Syndexa Pharmaceuticals Corporation Compounds and methods for treatment of disorders associated with ER stress
IN2014CN04406A (enExample) * 2006-03-30 2015-09-04 Ptc Therapeutics Inc
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
IN2014KN02423A (enExample) 2006-04-07 2015-05-01 Vertex Pharma
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
AU2007257959A1 (en) 2006-06-09 2007-12-21 Kemia, Inc. Therapy using cytokine inhibitors
WO2008020227A2 (en) 2006-08-17 2008-02-21 Astrazeneca Ab Antibacterial pyrrolecarboxamides
WO2008029168A2 (en) 2006-09-08 2008-03-13 Summit Corporation Plc Treatment of duchenne muscular dystrophy
WO2008029152A2 (en) 2006-09-08 2008-03-13 Summit Corporation Plc Treatment of duchenne muscular dystrophy
EA016527B1 (ru) 2006-10-23 2012-05-30 ЭсДжиЭкс ФАРМАСЬЮТИКАЛЗ, ИНК. Триазолопиридазиновые модуляторы протеинкиназ
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
WO2008064259A2 (en) 2006-11-21 2008-05-29 Biokey, Inc. Solid dispersion composition comprising fluvastatin
JPWO2008065732A1 (ja) 2006-11-27 2010-03-04 日本ポリウレタン工業株式会社 アロファネート結合及びイソシアヌレート結合含有変性イソシアネート混合物の製造方法
US20080260820A1 (en) 2007-04-19 2008-10-23 Gilles Borrelly Oral dosage formulations of protease-resistant polypeptides
EP2164840A2 (en) 2007-05-09 2010-03-24 Vertex Pharmaceuticals Incorporated Modulators of cftr
NZ581419A (en) 2007-05-25 2012-05-25 Vertex Pharma Modulators of cystic fibrosis transmembrane conductance regulator
US8557823B2 (en) 2007-06-18 2013-10-15 Advanced Cancer Therapeutics, Llc Family of PFKFB3 inhibitors with anti-neoplastic activities
WO2008156783A2 (en) 2007-06-18 2008-12-24 University Of Louisville Research Foundation, Inc. Family of pfkfb3 inhibitors with anti-neoplastic activities
US20100292236A1 (en) 2007-07-19 2010-11-18 H. Lundbeck A/S 5-Membered Heterocyclic Amides And Related Compounds
WO2009023509A2 (en) 2007-08-09 2009-02-19 Vertex Pharmaceuticals Incorporated Therapeutic combinations useful in treating cftr related diseases
CN101827593B (zh) 2007-08-24 2013-07-24 沃泰克斯药物股份有限公司 用于治疗(特别是)囊性纤维化的异噻唑并吡啶酮
CA2699382C (en) 2007-09-14 2016-05-10 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
NZ600865A (en) 2007-09-14 2014-01-31 Vertex Pharma Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
BRPI0817897A2 (pt) 2007-11-02 2019-09-24 Methylgene Inc composto, composição, e, métodos de inibição da atividade hdac, e de tratamento de uma doença responsiva a um inibidor de atividade hdac
WO2009064959A1 (en) 2007-11-16 2009-05-22 Vertex Pharmaceuticals Incorporated Isoquinoline modulators of atp-binding cassette transporters
WO2009066775A1 (ja) 2007-11-22 2009-05-28 Zenyaku Kogyo Kabushikikaisha 複素環式化合物の非晶質体、それを含む固体分散体、薬剤、およびその製造法
PL2639223T3 (pl) 2007-12-07 2017-09-29 Vertex Pharmaceuticals Incorporated Sposób wytwarzania kwasów cykloalkilokarboksyamido-pirydyno-benzoesowych
EA201070699A1 (ru) 2007-12-07 2011-02-28 Вертекс Фармасьютикалз Инкорпорейтед Композиции 3-(6-(1-2,2-дифторбензо[d][1,3]диоксол-5-ил)циклопропанкарбоксамидо)-3-метилпиридин-2-ил)бензойной кислоты
PT2225230T (pt) 2007-12-07 2016-12-07 Vertex Pharma Formas sólidas de ácido 3-(6(1-(2,2-difluorobenzo[d][1,3] dioxol-5-il) ciclopropanocarboxamido)-3-metilpiridin-2-il) benzoico
US20100036130A1 (en) 2007-12-07 2010-02-11 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
ES2422741T3 (es) 2007-12-13 2013-09-13 Vertex Pharma Moduladores del regulador de la conductancia transmembrana de la fibrosis quística
US20090247521A1 (en) 2007-12-28 2009-10-01 Arete Therapeutics, Inc. Soluble epoxide hydrolase inhibitors for the treatment of endothelial dysfunction
NZ620944A (en) 2008-02-28 2015-02-27 Vertex Pharma Heteroaryl derivatives as cftr modulators
EP2271621B1 (en) 2008-03-31 2013-11-20 Vertex Pharmaceuticals Incorporated Pyridyl derivatives as cftr modulators
CA2721452A1 (en) 2008-04-16 2009-10-22 Biolipox Ab Bis-aryl compounds for use as medicaments
WO2009129501A1 (en) 2008-04-18 2009-10-22 Arete Therapeutics, Inc. Use of soluble epoxide hydrolase inhibitors in the treatment of smooth muscle disorders
CN104116736A (zh) 2008-04-24 2014-10-29 百时美施贵宝公司 埃坡霉素D在治疗包括阿尔茨海默病的τ相关疾病中的用途
US20110112193A1 (en) 2008-05-14 2011-05-12 Peter Nilsson Bis-aryl compounds for use as medicaments
US8822513B2 (en) 2010-03-01 2014-09-02 Gtx, Inc. Compounds for treatment of cancer
US9447049B2 (en) 2010-03-01 2016-09-20 University Of Tennessee Research Foundation Compounds for treatment of cancer
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
MX366161B (es) 2008-08-13 2019-07-01 Vertex Pharmaceutical Incorporated Composicion farmaceutica y su administracion.
US20100256184A1 (en) 2008-08-13 2010-10-07 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
US8895781B2 (en) 2008-09-04 2014-11-25 Georgetown University Transition metal-catalyzed C—H amination using unactivated amines
AR073578A1 (es) 2008-09-15 2010-11-17 Priaxon Ag Pirrolidin-2-onas
AU2009296271A1 (en) 2008-09-29 2010-04-01 Vertex Pharmaceuticals Incorporated Dosage units of 3-(6-(1-(2,2-difluorobenzo [d] [1,3] dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid
WO2010048149A2 (en) 2008-10-20 2010-04-29 Kalypsys, Inc. Heterocyclic modulators of gpr119 for treatment of disease
JP5645834B2 (ja) 2008-10-23 2014-12-24 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修飾因子
US20110257223A1 (en) 2008-10-23 2011-10-20 Vertex Pharmaceuticals Incorporated Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
NZ592685A (en) 2008-10-23 2013-04-26 Vertex Pharma Modulators of cystic fibrosis transmembrane conductance regulator
US8436014B2 (en) 2008-10-23 2013-05-07 Vertex Pharmaceutical Incorporated Solid forms of N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluorormethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihyroquinoline-3-carboxamide
UA104876C2 (uk) 2008-11-06 2014-03-25 Вертекс Фармасьютікалз Інкорпорейтед Модулятори atф-зв'язувальних касетних транспортерів
AU2008363828B2 (en) 2008-11-06 2016-09-08 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
WO2010060952A1 (en) 2008-11-27 2010-06-03 Boehringer Ingelheim International Gmbh 6,7,8,9-tetrahydro-5h-1,4,7,10a-tetraaza-cyclohept[f]indene derivatives, pharmaceutical compositions containing these compounds, their use and processes for preparing them
CA2750577A1 (en) 2008-12-03 2010-06-10 Presidio Pharmaceuticals, Inc. Inhibitors of hcv ns5a
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
US8946419B2 (en) 2009-02-23 2015-02-03 Mallinckrodt Llc (+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives
KR20100101054A (ko) 2009-03-07 2010-09-16 주식회사 메디젠텍 세포핵에서 세포질로의 ｇｓｋ３의 이동을 억제하는 화합물을 함유하는 세포핵에서 세포질로의 ｇｓｋ３ 이동에 의해 발생되는 질환의 치료 또는 예방용 약학적 조성물
HRP20181261T1 (hr) 2009-03-20 2018-12-14 Vertex Pharmaceuticals Incorporated Modulatori regulatora transmembranske provodljivosti cistične fibroze
SI2408750T1 (sl) 2009-03-20 2015-11-30 Vertex Pharmaceuticals Incorporated Postopek za izdelavo modulatorjev cistično-fibroznega transmembranskega regulatorja prevodnosti
GB0905641D0 (en) 2009-04-01 2009-05-13 Serodus As Compounds
AU2010238361B2 (en) 2009-04-16 2015-08-06 Fundacion Centro Nacional De Investigaciones Oncologicas Carlos Iii Imidazopyrazines for use as kinase inhibitors
WO2011005355A1 (en) 2009-05-07 2011-01-13 Achaogen, Inc. Combinations comprising a lpxc inhibitor and an antibiotic for use in the treatment of infections caused by gram-negative bacteria
CN102448937A (zh) 2009-05-29 2012-05-09 拉夸里亚创药株式会社 作为钙或钠通道阻滞剂的芳基取代羧酰胺衍生物
EP2264012A1 (de) 2009-06-03 2010-12-22 Bayer CropScience AG Heteroarylamidine und deren Verwendung als Fungizide
KR101256018B1 (ko) 2009-08-20 2013-04-18 한국과학기술연구원 단백질 키나아제 저해활성을 갖는 1,3,6-치환된 인돌 화합물
TW201111379A (en) 2009-09-09 2011-04-01 Vifor Int Ag Novel thiazole-and oxazole-hepcidine-antagonists
KR20120083416A (ko) 2009-09-17 2012-07-25 버텍스 파마슈티칼스 인코포레이티드 아자비시클릭 화합물의 제조 방법
US9334230B2 (en) 2009-09-18 2016-05-10 Nanyang Technological University Process of forming an amide
MX2012004792A (es) 2009-10-22 2013-02-01 Vertex Pharma Composiciones para el tratamiento de fibrosis quistica y otras enfermedades cronicas.
BR112012009584A2 (pt) 2009-10-23 2019-09-24 Vertex Pharma formas sólidas de n-(4-(7-azabiciclo[2.2.1]heptan-7-il)-2-(trifluorometil)fenil)-4-oxo-5-(trifluorometil)-1,4-di-hidroquinolina-3-carboxamida
WO2011050215A1 (en) 2009-10-23 2011-04-28 Vertex Pharmaceuticals Incorporated Process for preparing modulators of cystic fibrosis transmembrane conductance regulator
WO2011094890A1 (en) 2010-02-02 2011-08-11 Argusina Inc. Phenylalanine derivatives and their use as non-peptide glp-1 receptor modulators
EP2542081A4 (en) 2010-03-01 2013-07-31 Gtx Inc COMPOSITIONS FOR CANCER TREATMENT
WO2011115892A1 (en) 2010-03-15 2011-09-22 Griffin Patrick R Modulators of the retinoic acid receptor-related orphan receptors
US8247436B2 (en) 2010-03-19 2012-08-21 Novartis Ag Pyridine and pyrazine derivative for the treatment of CF
WO2011116397A1 (en) 2010-03-19 2011-09-22 Vertex Pharmaceuticals Incorporated Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
NZ602665A (en) 2010-03-25 2014-10-31 Vertex Pharma Solid forms of (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-n-(1-(2,3-dihyderoxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1h-indol-5-yl) cyclopropanecarboxamide
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
HRP20211752T1 (hr) 2010-04-07 2022-02-18 Vertex Pharmaceuticals Incorporated Farmaceutski pripravci 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioksol-5-il)ciklopropankarboksamido)-3-metilpiridin-2-il)benzojeve kiseline i njihova primjena
EP2555754B1 (en) 2010-04-07 2016-04-06 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
WO2011133953A1 (en) 2010-04-22 2011-10-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
KR20130056244A (ko) 2010-04-22 2013-05-29 버텍스 파마슈티칼스 인코포레이티드 시클로알킬카르복스아미도-인돌 화합물의 제조 방법
WO2011133956A1 (en) 2010-04-22 2011-10-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
AU2011242452A1 (en) 2010-04-22 2012-11-08 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
EP2571506B1 (en) 2010-05-20 2017-05-10 Cempra Pharmaceuticals, Inc. Processes for preparing macrolides and ketolides and intermediates therefor
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
US20120149708A1 (en) 2010-06-17 2012-06-14 George Mason University Modulators of viral transcription, and methods and compositions therewith
WO2012016133A2 (en) 2010-07-29 2012-02-02 President And Fellows Of Harvard College Ros1 kinase inhibitors for the treatment of glioblastoma and other p53-deficient cancers
UA110113C2 (xx) 2010-07-29 2015-11-25 Біциклічні азагетероциклічні карбоксаміди
CA2808501A1 (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
AU2011293135A1 (en) 2010-08-27 2013-04-11 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
WO2012049555A1 (en) 2010-10-13 2012-04-19 Lupin Limited Spirocyclic compounds as voltage-gated sodium channel modulators
JP2013540145A (ja) 2010-10-21 2013-10-31 ウニベルシテート デス ザールランデス コルチゾール依存性疾患の治療用の選択的ｃｙｐ１１ｂ１阻害剤
US8802700B2 (en) 2010-12-10 2014-08-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
WO2012079583A1 (en) 2010-12-15 2012-06-21 Aarhus Universitet System providing controlled delivery of gaseous co for carbonylation reactions
US9295754B2 (en) 2011-02-24 2016-03-29 Emory University Noggin inhibitory compositions for ossification and methods related thereto
US9464065B2 (en) 2011-03-24 2016-10-11 The Scripps Research Institute Compounds and methods for inducing chondrogenesis
CN102731492B (zh) 2011-03-30 2016-06-29 江苏恒瑞医药股份有限公司 环己烷类衍生物、其制备方法及其在医药上的应用
HUE047354T2 (hu) 2011-05-18 2020-04-28 Vertex Pharmaceuticals Europe Ltd Ivacaftor deuterizált származékai
US8945605B2 (en) 2011-06-07 2015-02-03 Parion Sciences, Inc. Aerosol delivery systems, compositions and methods
WO2013005057A1 (en) 2011-07-07 2013-01-10 Centro Nacional De Investigaciones Oncológicas (Cnio) New compounds
DK2753605T3 (da) 2011-09-09 2019-06-17 Lantheus Medical Imaging Inc Sammensætninger, fremgangsmåder, og systemer til syntesen og anvendelsen af billeddannelsesmidler
US9034879B2 (en) 2011-09-16 2015-05-19 Novartis Ag Heterocyclic compounds for the treatment of CF
ES2882807T3 (es) 2011-09-16 2021-12-02 Novartis Ag Heterociclil carboxamidas N-sustituidas
WO2013038378A1 (en) 2011-09-16 2013-03-21 Novartis Ag Pyridine amide derivatives
WO2013038373A1 (en) 2011-09-16 2013-03-21 Novartis Ag Pyridine amide derivatives
WO2013038381A1 (en) 2011-09-16 2013-03-21 Novartis Ag Pyridine/pyrazine amide derivatives
GB201116559D0 (en) 2011-09-26 2011-11-09 Univ Leuven Kath Novel viral replication inhibitors
WO2013067410A1 (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 - ca rboxamide) for treating cftr mediated diseases
US20140127901A1 (en) 2012-11-08 2014-05-08 Taiwan Semiconductor Manufacturing Company, Ltd. Low-k damage free integration scheme for copper interconnects
LT2776427T (lt) 2011-11-08 2017-04-10 Vertex Pharmaceuticals Incorporated Atp surišančios kasetės transporterių moduliatoriai
WO2013086131A1 (en) 2011-12-06 2013-06-13 The Trustees Of The University Of Pennsylvania Inhibitors targeting drug-resistant influenza a
US8772541B2 (en) 2011-12-15 2014-07-08 University of Pittsburgh—of the Commonwealth System of Higher Education Cannabinoid receptor 2 (CB2) inverse agonists and therapeutic potential for multiple myeloma and osteoporosis bone diseases
EP2606726A1 (de) 2011-12-21 2013-06-26 Bayer CropScience AG N-Arylamidine-substituierte trifluoroethylsulfid-Derivate als Akarizide und Insektizide
UA114619C2 (uk) 2012-01-25 2017-07-10 Вертекс Фармасьютікалз Інкорпорейтед СКЛАД 3-(6-(1-(2,2-ДИФТОРОБЕНЗО[d][1,3]ДІОКСОЛ-5-ІЛ)ЦИКЛОПРОПАНКАРБОКСАМІДО)-3-МЕТИЛПІРИДИН-2-ІЛ)БЕНЗОЙНОЇ КИСЛОТИ
HK1203840A1 (en) 2012-02-27 2015-11-06 沃泰克斯药物股份有限公司 Pharmaceutical composition and administration thereof
US9217050B2 (en) 2012-04-03 2015-12-22 3M Innovative Properties Company Crosslinkable composition comprising photobase generators
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
US9228101B2 (en) 2012-04-26 2016-01-05 Xerox Corporation Rapidly crystallizing phase change inks and methods for forming the same
US8888905B2 (en) 2012-04-26 2014-11-18 Xerox Corporation Fast crystallizing crystalline-amorphous ink compositions and methods for making the same
CA2813472A1 (en) 2012-04-26 2013-10-26 Xerox Corporation Rapid solidifying crystalline-amorphous inks
US9528016B2 (en) 2012-04-26 2016-12-27 Xerox Corporation Phase change inks comprising crystalline amides
US20130284054A1 (en) 2012-04-26 2013-10-31 Xerox Corporation Rapid solidifying crystalline-amorphous inks
EP2861577B1 (en) 2012-05-25 2017-01-04 Boehringer Ingelheim International GmbH Tertiary amines, medicaments containing said amines, use thereof and processes for the preparation thereof
GB2502624A (en) 2012-06-01 2013-12-04 Univ East Anglia Phosphoramide and phosphoramide-based catalysts and their use in intermolecular aziridination
EP2858645A1 (en) * 2012-06-08 2015-04-15 Vertex Pharmaceuticals Incorporated Pharmaceuticl compositions for the treatment of cftr -mediated disorders
JP6294314B2 (ja) 2012-06-08 2018-03-14 マサチューセッツ インスティテュート オブ テクノロジー ホスフィン配位パラジウムスルホナートパラダサイクル
FR2992317B1 (fr) 2012-06-22 2016-05-13 Diverchim Procede de preparation de peptides chiraux
WO2014002106A1 (en) 2012-06-25 2014-01-03 Cadila Healthcare Limited Novel compounds for the treatment of dyslipidemia and related diseases
DK2852668T3 (en) 2012-07-12 2016-05-30 Proqr Therapeutics Ii Bv Oligonucleotides TO COMPLETE A CHANGE IN SEQUENCE OF A target RNA molecule THERE IS IN A LIVING CELL
EP2872632A1 (en) 2012-07-12 2015-05-20 ProQR Therapeutics B.V. Exon replacement with stabilized artificial rnas
HK1209318A1 (en) * 2012-07-16 2016-04-01 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions of (r)-1-(2,2-diflurorbenzo[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
WO2014047110A2 (en) 2012-09-20 2014-03-27 Temple University - Of The Commonwealth System Of Higher Education Substituted alkyl diaryl derivatives, methods of preparation and uses
BR102012025405A2 (pt) 2012-10-05 2014-10-07 Fundação Universidade De Brasília Processo de obtenção de amidas via aminólise catalítica de ésteres e ácidos carboxílicos em líquidos iônicos
WO2014068893A1 (ja) 2012-10-29 2014-05-08 コニカミノルタ株式会社 位相差フィルム、円偏光板、及び画像表示装置
BR112015009913B1 (pt) 2012-11-02 2023-04-11 Vertex Pharmaceuticals Incorporated Comprimido compreendendo composto cristalino e dispersão sólida de composto substancialmente amorfo, seu processo de preparação, kit e método de preparação de um grânulo compreendendo composto cristalino e dispersão sólida de composto substancialmente amorfo
WO2014078479A2 (en) 2012-11-14 2014-05-22 The Board Of Regents Of The University Of Texas System INHIBITION OF HIF-2α HETERODIMERIZATION WITH HIF1β (ARNT)
JP6146990B2 (ja) 2012-11-16 2017-06-14 コンサート ファーマシューティカルズ インコーポレイテッド 重水素化されたｃｆｔｒ増強物質
HRP20181448T1 (hr) 2012-11-20 2018-11-02 Merial, Inc. Antihelmintski spojevi i sastavi te postupak za njihovu uporabu
ITMI20122065A1 (it) 2012-12-03 2014-06-04 Univ Padova Uso dei correttori del cftr nel trattamento delle patologie del muscolo striato
US20150346185A1 (en) 2012-12-05 2015-12-03 Institut National De La Sante Et De La Recherche Medicale (Inserm) Diagnosis of cystic fibrosis
EP2928532A4 (en) 2012-12-07 2016-06-29 Parion Sciences Inc NOSE CANNULA FOR THE ADMINISTRATION OF MEDICAMENTS IN AEROSOL FORM
US20140221424A1 (en) 2013-01-30 2014-08-07 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for use in the treatment of cystic fibrosis
US9452139B2 (en) 2013-03-14 2016-09-27 Novartis Ag Respirable agglomerates of porous carrier particles and micronized drug
US20140296164A1 (en) 2013-03-29 2014-10-02 Calista Therapeutics, Inc. Compositions and methods of use for cell targeted inhibitors of the Cystic Fibrosis transmembrane regulator associated ligand
US9382254B2 (en) 2013-05-07 2016-07-05 Galapagos Nv Compounds and pharmaceutical compositions thereof for the treatment of cystic fibrosis
WO2014190199A1 (en) 2013-05-24 2014-11-27 The California Institute For Biomedical Research Compounds for treatment of drug resistant and persistent tuberculosis
JP2014232188A (ja) 2013-05-29 2014-12-11 コニカミノルタ株式会社 セルロースアシレートフィルム、円偏光板及び画像表示装置
EP3013341A4 (en) 2013-06-26 2017-02-08 Proteostasis Therapeutics, Inc. Methods of modulating cftr activity
ES2691944T3 (es) 2013-08-08 2018-11-29 Galapagos Nv Tieno[2,3-c]piranos como moduladores CFTR
US9688990B2 (en) 2013-09-12 2017-06-27 Institut National De La Sante Et De La Recherche Medicale (Inserm) Methods and pharmaceutical compositions for treatment of cystic fibrosis
EP3046561B1 (en) 2013-09-20 2023-02-22 University of Pittsburgh - Of the Commonwealth System of Higher Education Compounds for treating prostate cancer
US9353078B2 (en) 2013-10-01 2016-05-31 New York University Amino, amido and heterocyclic compounds as modulators of rage activity and uses thereof
WO2015054337A1 (en) 2013-10-09 2015-04-16 Emory University Heterocyclic coupling catalysts and methods related thereto
KR102280372B1 (ko) 2013-11-12 2021-07-22 버텍스 파마슈티칼스 인코포레이티드 Cftr 매개된 질환 치료용 약제학적 조성물의 제조 방법
KR20150062652A (ko) 2013-11-29 2015-06-08 삼성전자주식회사 초음파 감응성 리포좀, 그를 포함한 약제학적 조성물 및 그를 이용하여 개체의 체내에 활성제를 전달하는 방법
BR112016015449A8 (pt) 2013-12-30 2020-06-09 Lifesci Pharmaceuticals Inc compostos inibidores terapêuticos, composição farmacêutica os compreendendo e uso dos mesmos
EP3114109A4 (en) 2014-03-07 2017-10-18 The Johns Hopkins University Inhibitors of histone lysine specific demethylase (lsd1) and histone deacetylases (hdacs)
JP2015172005A (ja) 2014-03-11 2015-10-01 国立大学法人 東京大学 鉄触媒によるカップリング化合物の製造方法
CA2942387A1 (en) 2014-03-13 2015-09-17 Proteostasis Therapeutics, Inc. Compounds, compositions and methods of increasing cftr actvity
EP3116501A1 (en) 2014-03-13 2017-01-18 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing cftr activity
ES2885181T3 (es) 2014-04-15 2021-12-13 Vertex Pharma Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística
CA2947982C (en) 2014-05-08 2022-11-29 Phasebio Pharmaceuticals, Inc. Methods and compositions for treating cystic fibrosis
US10864213B2 (en) 2014-05-12 2020-12-15 Verona Pharma Plc Treatment
AU2015258904A1 (en) 2014-05-16 2016-11-17 Liqwd, Inc. Keratin treatment formulations and methods
ES2842592T3 (es) 2014-05-19 2021-07-14 Boehringer Ingelheim Animal Health Usa Inc Compuestos antihelmínticos
US9399623B2 (en) 2014-06-05 2016-07-26 Merck Patent Gmbh Quinoline derivatives and their use in neurodegenerative diseases
WO2015196071A1 (en) 2014-06-19 2015-12-23 Proteostasis Therapeutics, Inc. Compounds, compositions and methods of increasing cftr activity
WO2016025448A2 (en) 2014-08-13 2016-02-18 Akeso Biomedical, Inc. Antimicrobial compounds and compositions, and uses thereof
GB201415381D0 (en) 2014-08-29 2014-10-15 Algipharma As Inhalable powder formulations of alginate oligomers
WO2016040505A1 (en) 2014-09-10 2016-03-17 Epizyme, Inc. Smyd inhibitors
WO2016050210A1 (zh) 2014-10-01 2016-04-07 厦门赛诺邦格生物科技有限公司 一种多官能化聚乙二醇衍生物及其制备方法
WO2016050208A1 (zh) 2014-10-01 2016-04-07 厦门赛诺邦格生物科技有限公司 一种多官能化聚乙二醇衍生物修饰的生物相关物质
WO2016050209A1 (zh) 2014-10-01 2016-04-07 厦门赛诺邦格生物科技有限公司 一种异官能化聚乙二醇衍生物、制备方法及其生物相关物质
CN104725628B (zh) 2014-10-01 2018-04-17 厦门赛诺邦格生物科技股份有限公司 一种含可降解基团的单一官能化支化聚乙二醇、制备方法及其生物相关物质
US9855249B2 (en) 2014-10-02 2018-01-02 Flatley Discovery Lab, Llc Isoxazole compounds and methods for the treatment of cystic fibrosis
WO2016057572A1 (en) 2014-10-06 2016-04-14 Mark Thomas Miller Modulators of cystic fibrosis transmembrane conductance regulator
ES2971157T3 (es) 2014-10-06 2024-06-03 Apm Therapeutics 1 Inc Compuestos de triazolopiridina y métodos para el tratamiento de la fibrosis quística
JP6746569B2 (ja) 2014-10-07 2020-08-26 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Ｖｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ 嚢胞性線維症膜貫通コンダクタンス制御因子のモジュレーターの共結晶
EP3204010A1 (en) 2014-10-08 2017-08-16 Nivalis Therapeutics, Inc. Methods for the treatment of cystic fibrosis
US20160108406A1 (en) 2014-10-08 2016-04-21 University Of Iowa Research Foundation Method of regulating cftr expression and processing
GB201418892D0 (en) 2014-10-23 2014-12-10 Proqr Therapeutics B V DNA editing
EP3212201B1 (en) 2014-10-28 2022-10-19 BCI Pharma Nucleoside kinase inhibitors
CA2966023A1 (en) 2014-10-31 2016-05-06 Abbvie S.A.R.L. Substituted tetrahydropyrans and method of use
EP3212189B1 (en) 2014-10-31 2020-09-09 AbbVie Overseas S.à r.l. Substituted chromanes and method of use
DK3221692T3 (da) 2014-11-18 2021-08-23 Vertex Pharma Fremgangsmåde til udførsel af tests med høj kapacitet ved hjælp af højtryksvæskekromatografi
WO2016086015A1 (en) 2014-11-25 2016-06-02 University Of Rochester Myoglobin-based catalysts for carbene transfer reactions
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
CA2971855A1 (en) 2014-12-23 2016-06-30 Proteostasis Therapeutics, Inc. Derivatives of 5-(hetero)arylpyrazol-3-carboxylic amide or 1-(hetero)aryltriazol-4-carboxylic amide useful for the treatment of inter alia cystic fibrosis
US10344023B2 (en) 2014-12-23 2019-07-09 Proteostasis Therapeutics, Inc. Derivatives of 3-heteroarylisoxazol-5-carboxylic amide useful for the treatment of inter alia cystic fibrosis
WO2016105477A1 (en) 2014-12-23 2016-06-30 Proteostasis Therapeutics, Inc Derivatives of 5-phenyl- or 5-heteroarylthiazol-2-carboxylic amide useful for the treatment of inter alia cystic fibrosis
MA41253A (fr) 2014-12-23 2017-10-31 Proteostasis Therapeutics Inc Composés, compositions et procédés pour augmenter l'activité du cftr
CN113563451A (zh) 2014-12-24 2021-10-29 凯思生物技术公司 用于治疗呼吸系统疾病的新型PI3Kγ抑制剂肽
WO2016109362A1 (en) 2014-12-31 2016-07-07 Auspex Pharmaceuticals, Inc. Cyclopropanecarboxamide modulators of cystic fibrosis transmembrane conductance regulator
WO2016107603A1 (zh) 2015-01-01 2016-07-07 成都贝斯凯瑞生物科技有限公司 取代氮杂环衍生物及其应用
US20180147187A1 (en) 2015-01-12 2018-05-31 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing cftr activity
WO2016160945A1 (en) 2015-03-31 2016-10-06 Concert Pharmaceuticals, Inc. Deuterated vx-661
US20180280349A1 (en) 2017-03-28 2018-10-04 Vertex Pharmaceuticals Incorporated Methods of treating cystic fibrosis in patients with residual function mutations

Also Published As

Publication number Publication date
CY1124568T1 (el) 2022-07-22
TR201809684T4 (tr) 2018-07-23
US10206877B2 (en) 2019-02-19
LT3131582T (lt) 2018-10-25
EP3424534B1 (en) 2021-06-02
IL266286B1 (en) 2023-07-01
EP3424534A1 (en) 2019-01-09
PL3131582T3 (pl) 2018-10-31
IL266286B2 (en) 2023-11-01
ZA201606418B (en) 2019-12-18
CL2016002600A1 (es) 2017-08-18
PT3131582T (pt) 2018-10-08
HUE062736T2 (hu) 2023-12-28
AU2015247850A1 (en) 2016-10-06
EP3925607B9 (en) 2025-07-16
RS57476B1 (sr) 2018-10-31
SMT201800409T1 (it) 2018-09-13
RU2016144479A (ru) 2018-05-16
ES2675858T3 (es) 2018-07-13
JP2017511344A (ja) 2017-04-20
MX2016013301A (es) 2017-01-18
CN110840847B (zh) 2022-07-29
DK3131582T3 (en) 2018-08-06
CA2944140C (en) 2022-10-04
RS57476B9 (sr) 2021-10-29
KR102447581B1 (ko) 2022-09-28
SG10201913575VA (en) 2020-02-27
EP3925607B1 (en) 2023-06-28
JP6543268B2 (ja) 2019-07-10
CN106163517A (zh) 2016-11-23
US10980746B2 (en) 2021-04-20
CN110840847A (zh) 2020-02-28
PT3424534T (pt) 2021-08-10
UA124567C2 (uk) 2021-10-13
EP3925607A1 (en) 2021-12-22
IL266286A (en) 2019-06-30
CA2944140A1 (en) 2015-10-22
DK3925607T3 (da) 2023-08-21
NZ724488A (en) 2023-10-27
HRP20181194T1 (hr) 2018-09-21
RU2744460C2 (ru) 2021-03-09
LT3424534T (lt) 2021-11-10
DK3424534T3 (da) 2021-07-26
AU2019250116A1 (en) 2019-10-31
IL248359B (en) 2019-05-30
SMT202100461T1 (it) 2021-09-14
SI3424534T1 (sl) 2021-08-31
HUE055369T2 (hu) 2021-11-29
SI3925607T1 (sl) 2023-10-30
PT3925607T (pt) 2023-09-26
EP3131582B1 (en) 2018-05-23
FI3925607T3 (fi) 2023-08-28
WO2015160787A1 (en) 2015-10-22
CL2020002757A1 (es) 2021-02-26
BR112016023422A8 (pt) 2021-07-20
SMT202300255T1 (it) 2023-09-06
CY1120582T1 (el) 2019-07-10
AU2015247850B2 (en) 2019-07-18
HUE039062T2 (hu) 2018-12-28
RS62140B1 (sr) 2021-08-31
HRP20211012T1 (hr) 2021-09-17
US20190125674A1 (en) 2019-05-02
MX2021013638A (es) 2022-01-06
IL303422A (en) 2023-08-01
US20150320736A1 (en) 2015-11-12
RU2016144479A3 (enExample) 2018-05-16
US20210308053A1 (en) 2021-10-07
US11951212B2 (en) 2024-04-09
BR112016023422A2 (pt) 2017-08-15
SI3131582T1 (sl) 2018-09-28
EP4223294A1 (en) 2023-08-09
PL3424534T3 (pl) 2021-11-22
LT3925607T (lt) 2023-11-27
IL248359A0 (en) 2016-11-30
RS64400B9 (sr) 2025-10-31
EP3131582A1 (en) 2017-02-22
ES2957761T3 (es) 2024-01-25
RS64400B1 (sr) 2023-08-31
NZ763453A (en) 2023-10-27
CN106163517B (zh) 2020-08-14
KR20160145124A (ko) 2016-12-19
HRP20230709T1 (hr) 2023-10-13
MX387720B (es) 2025-03-12
PL3925607T3 (pl) 2023-10-30
AU2019250116B2 (en) 2021-09-16
SG11201607670XA (en) 2016-10-28

Similar Documents

Publication Publication Date Title
ES2885181T3 (es) Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística
HK40098013A (en) Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
HK40064071B (en) Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
HK40064071A (en) Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
BR112016023422B1 (pt) Dispersão seca por spray, composições farmacêuticas e seus usos no tratamento de fibrose cística
HK40001890A (en) Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
HK40001890B (en) Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
HK1233179A1 (en) Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
HK1233179B (en) Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
NZ763453B2 (en) Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
NZ724488B2 (en) Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases