HRP20151141T1 - Derivati piridila kao modulatori cftr - Google Patents

Derivati piridila kao modulatori cftr Download PDF

Info

Publication number
HRP20151141T1
HRP20151141T1 HRP20151141TT HRP20151141T HRP20151141T1 HR P20151141 T1 HRP20151141 T1 HR P20151141T1 HR P20151141T T HRP20151141T T HR P20151141TT HR P20151141 T HRP20151141 T HR P20151141T HR P20151141 T1 HRP20151141 T1 HR P20151141T1
Authority
HR
Croatia
Prior art keywords
image
compound according
aryl
independently
alkylidene
Prior art date
Application number
HRP20151141TT
Other languages
English (en)
Inventor
Sara Hadida-Ruah
Mark Miller
Jinglan Zhou
Brian Bear
Peter Grootenhuis
Original Assignee
Vertex Pharmaceuticals Incorporated
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 Incorporated filed Critical Vertex Pharmaceuticals Incorporated
Publication of HRP20151141T1 publication Critical patent/HRP20151141T1/hr

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic 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
    • C07D213/02Heterocyclic 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
    • C07D213/04Heterocyclic 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
    • C07D213/60Heterocyclic 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
    • C07D213/72Nitrogen atoms
    • C07D213/75Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic 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
    • C07D213/02Heterocyclic 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
    • C07D213/04Heterocyclic 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
    • C07D213/60Heterocyclic 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
    • C07D213/72Nitrogen atoms
    • C07D213/74Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/02Nasal agents, e.g. decongestants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/02Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02Muscle relaxants, e.g. for tetanus or cramps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/04Artificial tears; Irrigation solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/06Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/14Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/18Drugs for disorders of the endocrine system of the parathyroid hormones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/48Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10Antioedematous agents; Diuretics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/12Antidiuretics, e.g. drugs for diabetes insipidus
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pulmonology (AREA)
  • Obesity (AREA)
  • Psychology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Urology & Nephrology (AREA)
  • Otolaryngology (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Dermatology (AREA)
  • Psychiatry (AREA)
  • Emergency Medicine (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Claims (36)

1. Spoj s formulom I: [image] ili njegova farmaceutski prihvatljiva sol, naznačen time da: RN je H, alkil, aril, heteroaril, aralkil, cikloalkil, ili heterocikloalkil; A je 3 člani monociklički prsten; B je proizvoljno kondenziran na 5-7 člani prsten odabran iz skupine koju čine cikloalifatski prstenovi, aril, heterociklički prstenovi, i heteroaril; R1 je halogen, alkil, OH, alkoksi, tioalkil, trifluorometoksi; ili dva R1 na susjednim atomima, zajedno, tvore [image] pri čemu J je odabran iz skupine koju čine CH2, CF2, ili C(CH3)2; W je neovisno veza ili (C1-C6) alkilidenski lanac pri čemu su do dvije jedinice metilena iz W neovisno zamijenjene s -O-, -S-, -SO2-, ili-NR'-; R' je neovisno H, alkil, aril, heteroaril, aralkil, cikloalkil, ili heterociklil; RW je neovisno H, CN, NO2, N(R)2, CF3, OCF3, OH, OR, CO2R, C(O)N(R)2, -O(C1-C6)alkiliden-OR, -O(C1-C6)alkiliden-N(R)2, -O(C1-C6)alkiliden-heterociklil, ili alifatski, cikloalifatski, aril, ariloksi, heterociklički, ili heteroarilni ostatak, pri čemu, kada je supstituiran, Rw je supstituiran s do dva R2; R2 je halogen, CN, NO2, CF3, OCF3, OR, OC(O)R, OC(O)N(R)2, SR, S(O)R, SO2R, SO2N(R)2, SO3R, C(O)R, CO2R, C(O)N(R)2, N(R)2, NRC(O)R, NRCO2R, NRC(O)N(R)2, NRSO2R, B(OR)2, ili NRSO2N(R)2; R je neovisno H, alkil, cikloalkil, heterociklil, aril, ili heteroaril; n je 1 ili 2; w je cijeli broj od 0 do uključujući 4; i x je cijeli broj od 0 do uključujući 5; uz uvjet da kada W je veza i Rw je cikloalifatski, heterocikloalifatski, aril, ili heteroarilni ostatak, -W-Rw je vezan na 3- ili 4- položaj u piridil prstenu.
2. Spoj prema zahtjevu 1, naznačen time da J je CH2.
3. Spoj prema zahtjevu 1, naznačen time da J je CF2.
4. Spoj prema zahtjevu 1, naznačen time da RN je H ili alkil.
5. Spoj prema zahtjevu 1, naznačen time da W je veza.
6. Spoj prema zahtjevu 1, naznačen time da W je (C1-C6) alkilidenski lanac.
7. Spoj prema zahtjevu 1, naznačen time da W je odabran iz skupine koju čine -CH2-, -NH-, -O-, i -OCH2-.
8. Spoj prema zahtjevu 1, naznačen time da Rw je odabran iz skupine koju čine H, OH, heterociklil, aril, fenil, heteroaril, piridil, alkoksi, cikloalkil, i cikloheksil.
9. Spoj prema zahtjevu 1, naznačen time da-W-Rw je aciklički.
10. Spoj prema zahtjevu 1, naznačen time da -W-Rw je aril, heteroaril, cikloalifatski, ili heterocikloalifatski prsten.
11. Spoj prema zahtjevu 1, naznačen time da -W(Rw)n je odabran od slijedećeg: -F, -CH3, -CH2CH3, -CN, -CF3, -CONH2, -CH2CH(CH3)2, [image] [image] [image] [image] [image] [image] [image] [image] [image] [image]
12. Spoj prema zahtjevu 1, naznačen time da -W(Rw)n je odabran od slijedećeg: [image] [image]
13. Spoj prema zahtjevu 1, koji ima formulu Ia: [image] ili njegova farmaceutski prihvatljiva sol, naznačen time da: J je CH2 ili CF2; W je neovisno veza ili (C1-C6) alkilidenski lanac po izboru supstituiran s R2 pri čemu su do dvije jedinice metilena iz W neovisno zamijenjene s -O-, ili -NR'-; R' je neovisno H ili alkil; RW je neovisno H, CN, N(R)2, CF3, OH, CO2R, C(O)N(R)2, -O(C1-C6)alkiliden-OR, -O(C1-C6)alkiliden-N(R)2, -O(C1-C6)alkiliden-heterociklil, ili alifatski, cikloalifatski, aril, ariloksi, heterociklički, ili heteroarilni ostatak, pri čemu, kada je supstituiran, Rw je supstituiran s do dva R2; R2 je halogen, OR, CO2R, C(O)N(R)2, SO2N(R)2, B(OR)2, ili N(R)2; R je neovisno H, alkil, cikloalkil, heterociklil, aril, ili heteroaril; n je 1 ili 2; i w je cijeli broj od 0 do uključujući 4; uz uvjet da kada W je veza i Rw je cikloalifatski, heterocikloalifatski, aril, ili heteroarilni ostatak, -W-Rw je vezan na 3- ili 4- položaj u piridil prstenu.
14. Spoj prema zahtjevu 13, naznačen time da J je CH2.
15. Spoj prema zahtjevu 13, naznačen time da J je CF2.
16. Spoj prema zahtjevu 13, naznačen time da -W-Rw je aciklički.
17. Spoj prema zahtjevu 13, naznačen time da -W-Rw je aril, heteroaril, cikloalifatski, ili heterocikloalifatski prsten.
18. Spoj prema zahtjevu 13, naznačen time da -W(Rw)n je je odabran od slijedećeg: -F, -CH3, -CH2CH3, -CN, -CF3, -CONH2, -CH2CH(CH3)2, [image] [image] [image] [image] [image] [image] [image] [image] [image] [image]
19. Spoj prema zahtjevu 13, naznačen time da -W(Rw)n je odabran od slijedećeg: [image] [image]
20. Spoj prema zahtjevu 1, koji ima formulu Ib: [image] ili njegova farmaceutski prihvatljiva sol, naznačen time da: R1 je halogen, alkil, OH, alkoksi, tioalkil, trifluorometoksi; ili dva R1 na susjednim atomima, zajedno, tvore [image] pri čemu J je odabran iz skupine koju čine CH2, CF2, ili C(CH3)2; W je -NR' ili -CH2-; R' je neovisno H ili alkil; RW je neovisno H, CN, N(R)2, CF3, OH, CO2R, C(O)N(R)2, -O(C1-C6)alkiliden-OR, -O(C1-C6)alkiliden-N(R)2, -O(C1-C6)alkiliden-heterociklil, ili alifatski, cikloalifatski, aril, ariloksi, heterociklički, ili heteroarilni ostatak, pri čemu, kada je supstituiran, Rw je supstituiran s do dva R2; R2 je halogen, OR, CO2R, C(O)N(R)2, SO2N(R)2, B(OR)2, ili N(R)2; R je neovisno H, alkil, cikloalkil, heterociklil, aril, ili heteroaril; n je 1 ili 2; w je cijeli broj od 0 do uključujući 4; i x je cijeli broj od 0 do uključujući 5.
21. Spoj prema zahtjevu 20, naznačen time da dva R1 na susjednim atomima, zajedno, tvore [image] i J je CH2.
22. Spoj prema zahtjevu 20, naznačen time da dva R1 na susjednim atomima, zajedno, tvore [image] i J je CF2.
23. Spoj prema zahtjevu 20, naznačen time da -W(Rw)n je odabran od slijedećeg: -CH3, -CH2CH3, -CH2CH(CH3)2, [image] [image] [image] [image] [image] [image] [image] [image] [image]
24. Spoj prema zahtjevu 1, koji ima formulu Ic: [image] ili njegova farmaceutski prihvatljiva sol, naznačen time da: R1 je halogen, alkil, OH, alkoksi, tioalkil, trifluorometoksi; ili dva R1 na susjednim atomima, zajedno, tvore [image] pri čemu J je odabran iz skupine koju čine CH2, CF2, ili C(CH3)2; W je -NR' ili -CH2-; R' je neovisno H ili alkil; RW je neovisno H, CN, N(R)2, CF3, OH, CO2R, C(O)N(R)2, -O(C1-C6)alkiliden-OR, -O(C1-C6)alkiliden-N(R)2, -O(C1-C6)alkiliden-heterociklil, ili alifatski, cikloalifatski, aril, ariloksi, heterociklički, ili heteroarilni ostatak, pri čemu, kada je supstituiran, Rw je supstituiran s do dva R2; R2 je halogen, OR, CO2R, C(O)N(R)2, SO2N(R)2, B(OR)2, ili N(R)2; R je neovisno H, alkil, cikloalkil, heterociklil, aril, ili heteroaril; n je 1 ili 2; w je cijeli broj od 0 do uključujući 4; i x je cijeli broj od 0 do uključujući 5.
25. Spoj prema zahtjevu 24, naznačen time da dva R1 na susjednim atomima, zajedno, tvore [image] i J je CH2.
26. Spoj prema zahtjevu 24, naznačen time da dva R1 na susjednim atomima, zajedno, tvore [image] i J je CF2.
27. Spoj prema zahtjevu 24, naznačen time da -W(Rw)n je odabran od slijedećeg: -CH3, -CH2CH3, -CH2CH(CH3)2, [image] [image] [image] [image] [image] [image] [image] [image] [image]
28. Spoj naznačen time da je odabran od sljedećih spojeva [image] [image] [image] [image] [image] [image]
29. Farmaceutski pripravak naznačen time da sadrži (i) spoj prema zahtjevu 1; i (ii) farmaceutski prihvatljiv nosač.
30. Pripravak prema zahtjevu 29, naznačen time da dodatno sadrži dodatno sredstvo koje je odabrano od mukolitičkog sredstva, bronhodilatatora, antibiotika, antiinfektivnog sredstva, protuupalnog sredstva, modulatora CFTR koji nije spoj prema zahtjevu 1, te nutritivnog sredstva.
31. Pripravak prema zahtjevu 30, naznačen time da dodatno sredstvo je N-(5-hidroksi-2,4-ditert-butil-fenil)-4-okso-1H-kinolin-3-karboksamid.
32. In vitro postupak za modulaciju ABC transportera u staničnoj membrani naznačen time da sadrži korak dovođenje u kontakt navedene stanice sa spojem prema zahtjevu 1.
33. In vitro postupak prema zahtjevu 31, naznačen time da ABC transporter je CFTR.
34. Pripravak prema bilo kojem zahtjevu od 1 do 28 ili farmaceutski pripravak prema zahtjevima 29 do 31 naznačen time da je za upotrebu za liječenje stanja, bolesti, ili poremećaja odabranih od cistične fibroze, nasljednog emfizema, nasljedne hemokromatoze, nedostataka koagulacije-fibrinolize, kao što je nedostatak proteina C, nasljedni angioedem tipa 1, nedostataka obrade lipida, kao što je obiteljska hiperkolesterolemija, kilomikronemija tip 1, abetalipoproteinemija, bolesti lizosomskog nakupljanja, kao što je bolest I-stanica/pseudo-Hurler, mukopolisaharidoze, Sandhof/Tay-Sachs, Crigler-Najjar tip II, poliendokrinopatija/ hiperinzulinemija, dijabetes melitus, Laronov sindrom patuljastog rasta, nedostatak mijeloperoksidaze, primarni hiperparatiroidizam, melanom, CDG glikogenoza tip I, nasljedni emfizem, kongenitalna hipertireoza, osteogenesis imperfecta, nasljedna hipofibrinogenemija, nedostatak ACT, dijabetes insipidus (DI), neurohipofizni DI, nefrogeni DI, Charcot-Marie Tooth sindrom, Pelizaeus-Merzbacherova bolest, neurodegenerativne bolesti kao što su Alzheimerova bolest, Parkinsonova bolest, amiotrofna lateralna skleroza, progresivna supranuklearna paraliza, Pickova bolest, nekoliko poliglutaminskih neuroloških poremećaja kao što su Huntingtonov poremećaj, spinocerebelarna ataksija tip I, spinalna i bulbarna mišićna atrofija, dentatorubralna palidolujzianska atrofija, te miotonična distrofija, kao i spongiformne encefalopatije, kao što je nasljedna Creutzfeldt-Jakobova bolest, Fabrijeva bolest, Gerstmann-Straussler-Scheinkerov sindrom, KOPB, bolest suhog oka, te Sjogrenova bolest.
35. Spoj prema bilo kojem od zahtjeva 1 do 28 ili farmaceutski pripravak prema bilo kojem od zahtjeva 29 do 31 naznačen time da je za upotrebu u liječenju cistične fibroze.
36. Komplet za uporabu za mjerenje aktivnosti ABC transportera ili njegovog fragmenta u biološkom uzorku in vitro ili in vivo, naznačen time da sadrži: (i) prvi pripravak koji sadrži spoj u skladu sa zahtjevom 1; te (ii) instrukcije za: a) dovođenje u kontakt pripravka s biološkim uzorkom; b) mjerenje aktivnosti navedenog ABC transportera ili njegovog fragmenta.
HRP20151141TT 2008-03-31 2015-10-27 Derivati piridila kao modulatori cftr HRP20151141T1 (hr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4077608P 2008-03-31 2008-03-31
EP12188920.8A EP2615085B1 (en) 2008-03-31 2009-03-25 Pyridyl derivatives as CFTR modulators

Publications (1)

Publication Number Publication Date
HRP20151141T1 true HRP20151141T1 (hr) 2015-12-04

Family

ID=40790781

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20151141TT HRP20151141T1 (hr) 2008-03-31 2015-10-27 Derivati piridila kao modulatori cftr

Country Status (17)

Country Link
US (3) US8227615B2 (hr)
EP (3) EP2980077B1 (hr)
JP (3) JP5622285B2 (hr)
CN (2) CN101981011B (hr)
AU (1) AU2009231993B2 (hr)
CA (1) CA2718310C (hr)
CY (1) CY1116953T1 (hr)
DK (1) DK2615085T3 (hr)
ES (2) ES2442945T3 (hr)
HK (2) HK1198537A1 (hr)
HR (1) HRP20151141T1 (hr)
HU (1) HUE026220T2 (hr)
NZ (3) NZ600772A (hr)
PL (1) PL2615085T3 (hr)
PT (1) PT2615085E (hr)
SI (1) SI2615085T1 (hr)
WO (1) WO2009123896A1 (hr)

Families Citing this family (127)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
RU2006111093A (ru) 2003-09-06 2007-10-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Модуляторы атр-связывающих кассетных транспортеров
NZ547220A (en) * 2003-11-14 2009-12-24 Vertex Pharma Thiazoles and oxazoles useful as modulators of ATP-binding cassette transporters
BRPI0507278A (pt) * 2004-01-30 2007-06-26 Vertex Pharma moduladores dos transportadores do cassete de ligação ao atp
US7977322B2 (en) 2004-08-20 2011-07-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
BR122018075478B8 (pt) 2004-06-24 2023-10-31 Vertex Pharma moduladores de transportadores de cassete de ligação de atp
JP5143738B2 (ja) * 2005-08-11 2013-02-13 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物質
ES2439736T3 (es) 2005-11-08 2014-01-24 Vertex Pharmaceuticals Incorporated Moduladores heterocíclicos de transportadores de casete de unión a ATP
US7671221B2 (en) * 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
HUE049976T2 (hu) 2005-12-28 2020-11-30 Vertex Pharma N-[2,4-bisz(1,1-dimetil-etil)-5-hidroxi-fenil]-1,4-dihidro-4-oxo-kinolin-3-karboxamid amorf alakjának gyógyászati kompozíciói
CA2856037C (en) * 2005-12-28 2017-03-07 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US7645789B2 (en) 2006-04-07 2010-01-12 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
US10022352B2 (en) 2006-04-07 2018-07-17 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
RU2451018C2 (ru) 2006-04-07 2012-05-20 Вертекс Фармасьютикалз Инкорпорейтед Модуляторы атф-связывающих кассетных транспортеров
US8563573B2 (en) * 2007-11-02 2013-10-22 Vertex Pharmaceuticals Incorporated Azaindole derivatives as CFTR modulators
CN104447716A (zh) 2007-05-09 2015-03-25 沃泰克斯药物股份有限公司 Cftr调节剂
WO2008147797A2 (en) * 2007-05-25 2008-12-04 Vertex Pharmaceuticals Incorporated Ion channel modulators and methods of use
WO2009038913A2 (en) 2007-08-24 2009-03-26 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
CA2705562C (en) * 2007-11-16 2016-05-17 Vertex Pharmaceuticals Incorporated Isoquinoline modulators of atp-binding cassette transporters
WO2009076141A2 (en) * 2007-12-07 2009-06-18 Vertex Pharmaceuticals Incorporated Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cycklopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid
US20100036130A1 (en) 2007-12-07 2010-02-11 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
CA2989620C (en) * 2007-12-07 2022-05-03 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
CN101910156B (zh) 2007-12-07 2013-12-04 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)苯甲酸的固体形式
EP2271622B1 (en) 2008-02-28 2017-10-04 Vertex Pharmaceuticals Incorporated Heteroaryl derivatives as CFTR Modulators
PT2615085E (pt) 2008-03-31 2015-10-09 Vertex Pharma Derivados piridilo como moduladores cftr
CN102164587A (zh) * 2008-09-29 2011-08-24 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)苯甲酸的剂量单元
EA018891B1 (ru) 2008-10-23 2013-11-29 Вертекс Фармасьютикалз, Инкорпорейтед Модуляторы регулятора трансмембранной проводимости при муковисцидозе
SG10201504084QA (en) 2009-03-20 2015-06-29 Vertex Pharma Process for making modulators of cystic fibrosis transmembrane conductance regulator
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
DK3150198T3 (da) 2010-04-07 2021-11-01 Vertex Pharma Farmaceutiske sammensætninger af 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioxol-5-yl)-cyclopropancarboxamido)-3-methylpyriodin-2-yl)benzoesyre og indgivelse deraf
BR112012026257A2 (pt) 2010-04-07 2017-03-14 Vertex Pharma formas sólidas de ácido 3-(6-(1-(2-,2-difluorbenzo[d][1,3]dioxol-5-il)ciclopropanocarboxamido)-3-metilpiridin-2-il)benzóico
MX2012012204A (es) 2010-04-22 2012-12-05 Vertex Pharma Proceso para producir compuestos de cicloalquilcarboxamido-indol.
US8989186B2 (en) 2010-06-08 2015-03-24 Brocade Communication Systems, Inc. Virtual port grouping for virtual cluster switching
US9270486B2 (en) 2010-06-07 2016-02-23 Brocade Communications Systems, Inc. Name services for virtual cluster switching
US9716672B2 (en) 2010-05-28 2017-07-25 Brocade Communications Systems, Inc. Distributed configuration management for virtual cluster switching
US9461840B2 (en) 2010-06-02 2016-10-04 Brocade Communications Systems, Inc. Port profile management for virtual cluster switching
US8867552B2 (en) 2010-05-03 2014-10-21 Brocade Communications Systems, Inc. Virtual cluster switching
US9001824B2 (en) 2010-05-18 2015-04-07 Brocade Communication Systems, Inc. Fabric formation for virtual cluster switching
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
US9246703B2 (en) 2010-06-08 2016-01-26 Brocade Communications Systems, Inc. Remote port mirroring
US9608833B2 (en) 2010-06-08 2017-03-28 Brocade Communications Systems, Inc. Supporting multiple multicast trees in trill networks
US9628293B2 (en) 2010-06-08 2017-04-18 Brocade Communications Systems, Inc. Network layer multicasting in trill networks
US9807031B2 (en) 2010-07-16 2017-10-31 Brocade Communications Systems, Inc. System and method for network configuration
CN102133402B (zh) * 2011-03-24 2013-06-12 首都医科大学附属北京同仁医院 囊性纤维化跨膜转导调节因子抑制剂在制备治疗糖尿病药物中的应用
US9270572B2 (en) 2011-05-02 2016-02-23 Brocade Communications Systems Inc. Layer-3 support in TRILL networks
JP6219271B2 (ja) 2011-06-07 2017-10-25 パリオン・サイエンシィズ・インコーポレーテッド 治療の方法
US8945605B2 (en) 2011-06-07 2015-02-03 Parion Sciences, Inc. Aerosol delivery systems, compositions and methods
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
US8948056B2 (en) 2011-06-28 2015-02-03 Brocade Communication Systems, Inc. Spanning-tree based loop detection for an ethernet fabric switch
US9407533B2 (en) 2011-06-28 2016-08-02 Brocade Communications Systems, Inc. Multicast in a trill network
US9401861B2 (en) 2011-06-28 2016-07-26 Brocade Communications Systems, Inc. Scalable MAC address distribution in an Ethernet fabric switch
US8885641B2 (en) 2011-06-30 2014-11-11 Brocade Communication Systems, Inc. Efficient trill forwarding
US9736085B2 (en) 2011-08-29 2017-08-15 Brocade Communications Systems, Inc. End-to end lossless Ethernet in Ethernet fabric
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
EP2755652B1 (en) 2011-09-16 2021-06-02 Novartis AG N-substituted heterocyclyl carboxamides
US9699117B2 (en) 2011-11-08 2017-07-04 Brocade Communications Systems, Inc. Integrated fibre channel support in an ethernet fabric switch
ME02650B (me) 2011-11-08 2017-06-20 Vertex Pharma Modulatori atp- vezujućih kasetnih transportera
US9450870B2 (en) 2011-11-10 2016-09-20 Brocade Communications Systems, Inc. System and method for flow management in software-defined networks
WO2013093508A2 (en) * 2011-12-22 2013-06-27 Oslo University Hospital Hf Wnt pathway inhibitors
US8995272B2 (en) 2012-01-26 2015-03-31 Brocade Communication Systems, Inc. Link aggregation in software-defined networks
CN109966264A (zh) 2012-02-27 2019-07-05 沃泰克斯药物股份有限公司 药物组合物及其施用
US9742693B2 (en) 2012-02-27 2017-08-22 Brocade Communications Systems, Inc. Dynamic service insertion in a fabric switch
US9154416B2 (en) 2012-03-22 2015-10-06 Brocade Communications Systems, Inc. Overlay tunnel in a fabric switch
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
US9374301B2 (en) 2012-05-18 2016-06-21 Brocade Communications Systems, Inc. Network feedback in software-defined networks
US10277464B2 (en) 2012-05-22 2019-04-30 Arris Enterprises Llc Client auto-configuration in a multi-switch link aggregation
EP2853066B1 (en) 2012-05-23 2017-02-22 Brocade Communications Systems, Inc. Layer-3 overlay gateways
AU2013267504B2 (en) 2012-05-29 2017-11-02 Parion Sciences, Inc. Dendrimer like amino amides possessing sodium channel blocker activity for the treatment of dry eye and other mucosal diseases
AU2013270681A1 (en) 2012-06-08 2014-12-18 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for the treatment of CFTR -mediated disorders
AR092857A1 (es) 2012-07-16 2015-05-06 Vertex Pharma Composiciones farmaceuticas de (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-il)-n-(1-(2,3-dihidroxipropil)-6-fluoro-2-(1-hidroxi-2-metilpropan-2-il)-1h-indol-5-il)ciclopropancarboxamida y administracion de las mismas
US9602430B2 (en) 2012-08-21 2017-03-21 Brocade Communications Systems, Inc. Global VLANs for fabric switches
US9401872B2 (en) 2012-11-16 2016-07-26 Brocade Communications Systems, Inc. Virtual link aggregations across multiple fabric switches
ITMI20122065A1 (it) 2012-12-03 2014-06-04 Univ Padova Uso dei correttori del cftr nel trattamento delle patologie del muscolo striato
BR112015014178A2 (pt) 2012-12-17 2017-07-11 Parion Sciences Inc compostos de 3,5-diamino-6-cloro-n-(n-(4-fenilbutil)carbamimidoil) pirazina-2- carboxamida
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
PT2931713T (pt) 2012-12-17 2017-02-22 Parion Sciences Inc Derivados de cloro-pirazina carboxamida úteis para o tratamento de doenças favorecidas por insuficiente hidratação das mucosas
US9548926B2 (en) 2013-01-11 2017-01-17 Brocade Communications Systems, Inc. Multicast traffic load balancing over virtual link aggregation
US9350680B2 (en) 2013-01-11 2016-05-24 Brocade Communications Systems, Inc. Protection switching over a virtual link aggregation
US9413691B2 (en) 2013-01-11 2016-08-09 Brocade Communications Systems, Inc. MAC address synchronization in a fabric switch
US9565113B2 (en) 2013-01-15 2017-02-07 Brocade Communications Systems, Inc. Adaptive link aggregation and virtual link aggregation
US9565099B2 (en) 2013-03-01 2017-02-07 Brocade Communications Systems, Inc. Spanning tree in fabric switches
WO2014145750A1 (en) 2013-03-15 2014-09-18 Brocade Communications Systems, Inc. Scalable gateways for a fabric switch
US9699001B2 (en) 2013-06-10 2017-07-04 Brocade Communications Systems, Inc. Scalable and segregated network virtualization
US9565028B2 (en) 2013-06-10 2017-02-07 Brocade Communications Systems, Inc. Ingress switch multicast distribution in a fabric switch
CN104224781B (zh) * 2013-06-21 2018-09-25 中国医学科学院医药生物技术研究所 一组2-酰胺基-3-烷氧基取代的吡啶类化合物及其新用途
US20160168132A1 (en) * 2013-07-31 2016-06-16 Minoryx Therapeutics S.L. Di(hetero)arylamides and sulfonamides, methods for their preparation and therapeutic uses thereof
US9912612B2 (en) 2013-10-28 2018-03-06 Brocade Communications Systems LLC Extended ethernet fabric switches
US10231932B2 (en) 2013-11-12 2019-03-19 Vertex Pharmaceuticals Incorporated Process of preparing pharmaceutical compositions for the treatment of CFTR mediated diseases
EP2878339A1 (en) 2013-12-02 2015-06-03 Siena Biotech S.p.A. SIP3 antagonists
US9548873B2 (en) 2014-02-10 2017-01-17 Brocade Communications Systems, Inc. Virtual extensible LAN tunnel keepalives
US10581758B2 (en) 2014-03-19 2020-03-03 Avago Technologies International Sales Pte. Limited Distributed hot standby links for vLAG
US10476698B2 (en) 2014-03-20 2019-11-12 Avago Technologies International Sales Pte. Limited Redundent virtual link aggregation group
ES2957761T3 (es) 2014-04-15 2024-01-25 Vertex Pharma Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística
US10063473B2 (en) 2014-04-30 2018-08-28 Brocade Communications Systems LLC Method and system for facilitating switch virtualization in a network of interconnected switches
US9800471B2 (en) 2014-05-13 2017-10-24 Brocade Communications Systems, Inc. Network extension groups of global VLANs in a fabric switch
US10616108B2 (en) 2014-07-29 2020-04-07 Avago Technologies International Sales Pte. Limited Scalable MAC address virtualization
US9544219B2 (en) 2014-07-31 2017-01-10 Brocade Communications Systems, Inc. Global VLAN services
US9807007B2 (en) 2014-08-11 2017-10-31 Brocade Communications Systems, Inc. Progressive MAC address learning
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
US9524173B2 (en) 2014-10-09 2016-12-20 Brocade Communications Systems, Inc. Fast reboot for a switch
US9699029B2 (en) 2014-10-10 2017-07-04 Brocade Communications Systems, Inc. Distributed configuration management in a switch group
PL3212189T3 (pl) 2014-10-31 2021-03-08 AbbVie Overseas S.à r.l. Podstawione chromany i sposób użycia
BR112017009194A2 (pt) 2014-10-31 2017-12-26 Abbvie Sarl tetra-hidropiranos substituídos e método de uso
JP6494757B2 (ja) 2014-11-18 2019-04-03 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 ハイスループット試験高速液体クロマトグラフィーを行うプロセス
US9626255B2 (en) 2014-12-31 2017-04-18 Brocade Communications Systems, Inc. Online restoration of a switch snapshot
US9628407B2 (en) 2014-12-31 2017-04-18 Brocade Communications Systems, Inc. Multiple software versions in a switch group
US9942097B2 (en) 2015-01-05 2018-04-10 Brocade Communications Systems LLC Power management in a network of interconnected switches
US10003552B2 (en) 2015-01-05 2018-06-19 Brocade Communications Systems, Llc. Distributed bidirectional forwarding detection protocol (D-BFD) for cluster of interconnected switches
CN104788423B (zh) * 2015-03-13 2016-10-26 成都理工大学 一种新的囊性纤维化跨膜传导调节因子抑制剂
US9807005B2 (en) 2015-03-17 2017-10-31 Brocade Communications Systems, Inc. Multi-fabric manager
US10038592B2 (en) 2015-03-17 2018-07-31 Brocade Communications Systems LLC Identifier assignment to a new switch in a switch group
US10579406B2 (en) 2015-04-08 2020-03-03 Avago Technologies International Sales Pte. Limited Dynamic orchestration of overlay tunnels
US10439929B2 (en) 2015-07-31 2019-10-08 Avago Technologies International Sales Pte. Limited Graceful recovery of a multicast-enabled switch
US10171303B2 (en) 2015-09-16 2019-01-01 Avago Technologies International Sales Pte. Limited IP-based interconnection of switches with a logical chassis
US9912614B2 (en) 2015-12-07 2018-03-06 Brocade Communications Systems LLC Interconnection of switches based on hierarchical overlay tunneling
WO2018081167A1 (en) 2016-10-24 2018-05-03 Yumanity Therapeutics Compounds and uses thereof
CA3083000A1 (en) 2017-10-24 2019-05-02 Yumanity Therapeutics, Inc. Compounds and uses thereof
MX2020004930A (es) 2017-11-14 2020-08-27 Merck Sharp & Dohme Compuestos de biarilo sustituido novedosos como inhibidores de indolamina 2,3-dioxigenasa (ido).
BR112020019191A2 (pt) * 2018-03-23 2021-01-05 Yumanity Therapeutics, Inc. Compostos e seus usos
JP7560011B2 (ja) 2018-09-09 2024-10-02 カナートファーマ アーゲー 脳血管状態を治療するためのcftrモジュレーターの使用
CA3127791A1 (en) 2019-01-24 2020-07-30 Yumanity Therapeutics, Inc. Compounds and uses thereof
AU2020245349A1 (en) * 2019-03-22 2021-11-04 Janssen Pharmaceutica Nv Compounds and uses thereof
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
WO2024148267A1 (en) * 2023-01-05 2024-07-11 Empathbio, Inc. Heterocyclic propyl amine modulators of monoaminergic transporters

Family Cites Families (91)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1226048B (it) * 1981-12-14 1990-12-10 Medea Res Srl Composti ad attivita'antiinfiammatoria, processo per la loro preparazione e composizioni farmaceutiche relative
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
US5304121A (en) 1990-12-28 1994-04-19 Boston Scientific Corporation Drug delivery system making use of a hydrogel polymer coating
US5716981A (en) 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
US6099562A (en) 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
AU2010601A (en) * 1999-12-16 2001-07-03 Novartis Ag Organic compounds
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
TW200307539A (en) * 2002-02-01 2003-12-16 Bristol Myers Squibb Co Cycloalkyl inhibitors of potassium channel function
TW200403058A (en) * 2002-04-19 2004-03-01 Bristol Myers Squibb Co Heterocyclo inhibitors of potassium channel function
NZ538809A (en) 2002-09-30 2008-06-30 Univ California Thiazolidinone cystic fibrosis transmembrane conductance regulator protein inhibitors and uses thereof
WO2004080972A1 (en) 2003-03-12 2004-09-23 Vertex Pharmaceuticals Incorporated Pirazole modulators of atp-binding cassette transporters
SI3345895T1 (sl) 2003-04-11 2020-03-31 Ptc Therapeutics, Inc. Spojina 1,2,4-oksadiazol benzojske kisline in njena uporaba za supresijo nesmiselne in zdravljenje bolezni
US7696244B2 (en) 2003-05-16 2010-04-13 The Regents Of The University Of California Compounds having activity in increasing ion transport by mutant-CFTR and uses thereof
DE602004022819D1 (de) 2003-06-06 2009-10-08 Vertex Pharma Von atp-bindende kassette transportern
RU2006111093A (ru) 2003-09-06 2007-10-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Модуляторы атр-связывающих кассетных транспортеров
ZA200603515B (en) 2003-10-08 2007-11-28 Vertex Pharma Modulators of ATP-binding cassette transporters
NZ547220A (en) 2003-11-14 2009-12-24 Vertex Pharma Thiazoles and oxazoles useful as modulators of ATP-binding cassette transporters
BRPI0507278A (pt) 2004-01-30 2007-06-26 Vertex Pharma moduladores dos transportadores do cassete de ligação ao atp
US7977322B2 (en) 2004-08-20 2011-07-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
US7414037B2 (en) 2004-03-30 2008-08-19 The Regents Of The University Of California Hydrazide-containing CFTR inhibitor compounds and uses thereof
EP1765347A4 (en) 2004-06-04 2008-10-01 Univ California COMPOUNDS WITH ION TRANSPORTER HEALING EFFECT BY MUTANT CFTR AND ITS USE
BR122018075478B8 (pt) 2004-06-24 2023-10-31 Vertex Pharma moduladores de transportadores de cassete de ligação de atp
US8354427B2 (en) 2004-06-24 2013-01-15 Vertex Pharmaceutical Incorporated Modulators of ATP-binding cassette transporters
EP1815206B1 (en) 2004-10-13 2016-04-06 PTC Therapeutics, Inc. Compounds for nonsense suppression, and methods for their use
WO2006099256A2 (en) 2005-03-11 2006-09-21 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
RU2007138584A (ru) 2005-03-18 2009-04-27 Дзе Риджентс Оф Дзе Юниверсити Оф Калифорния (Us) Соединения, обладающие активностью для коррекции процессинга мутантного cftr, и их применение
ES2390804T3 (es) 2005-04-08 2012-11-16 Ptc Therapeutics, Inc. Composiciones de un 1,2,4-oxadiazol oralmente activo para terapia de supresión de la mutación sin sentido
ATE533749T1 (de) 2005-05-24 2011-12-15 Vertex Pharma Modulatoren von atp-bindenden kassettentransportern
JP5143738B2 (ja) 2005-08-11 2013-02-13 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物質
AU2006302371A1 (en) 2005-10-06 2007-04-19 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding cassette transporters
US20120232059A1 (en) 2005-11-08 2012-09-13 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette Transporters
ES2439736T3 (es) 2005-11-08 2014-01-24 Vertex Pharmaceuticals Incorporated Moduladores heterocíclicos de transportadores de casete de unión a ATP
US20090105272A1 (en) 2005-12-24 2009-04-23 Grootenhuis Peter D J Prodrugs of modulators of ABC transporters
CA2635214A1 (en) 2005-12-27 2007-07-05 Vertex Pharmaceuticals Incorporated Compounds useful in cftr assays and methods therewith
HUE049976T2 (hu) 2005-12-28 2020-11-30 Vertex Pharma N-[2,4-bisz(1,1-dimetil-etil)-5-hidroxi-fenil]-1,4-dihidro-4-oxo-kinolin-3-karboxamid amorf alakjának gyógyászati kompozíciói
CA2856037C (en) 2005-12-28 2017-03-07 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
RU2451018C2 (ru) 2006-04-07 2012-05-20 Вертекс Фармасьютикалз Инкорпорейтед Модуляторы атф-связывающих кассетных транспортеров
US7645789B2 (en) 2006-04-07 2010-01-12 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
AU2007249269A1 (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
US7754739B2 (en) * 2007-05-09 2010-07-13 Vertex Pharmaceuticals Incorporated Modulators of CFTR
CN101541759A (zh) * 2006-11-27 2009-09-23 诺瓦提斯公司 取代的二氢咪唑类及其在治疗肿瘤中的用途
CN104447716A (zh) * 2007-05-09 2015-03-25 沃泰克斯药物股份有限公司 Cftr调节剂
ES2548292T3 (es) 2007-05-25 2015-10-15 Vertex Pharmaceuticals Incorporated Moduladores del regulador de la conductancia transmembrana de la fibrosis quística
US20110177999A1 (en) 2007-08-09 2011-07-21 Vertex Pharmaceuticals Incorporated Therapeutic Combinations Useful in Treating CFTR Related Diseases
WO2009038913A2 (en) 2007-08-24 2009-03-26 Vertex Pharmaceuticals Incorporated Isothiazolopyridinones useful for the treatment of (inter alia) cystic fibrosis
CN101821266B (zh) 2007-09-14 2014-03-12 沃泰克斯药物股份有限公司 囊性纤维化跨膜通道调节因子的调节剂
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
CA2705562C (en) 2007-11-16 2016-05-17 Vertex Pharmaceuticals Incorporated Isoquinoline modulators of atp-binding cassette transporters
CN101910156B (zh) 2007-12-07 2013-12-04 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)苯甲酸的固体形式
CA2989620C (en) 2007-12-07 2022-05-03 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
US20100036130A1 (en) 2007-12-07 2010-02-11 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
WO2009076141A2 (en) 2007-12-07 2009-06-18 Vertex Pharmaceuticals Incorporated Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cycklopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid
JP5637859B2 (ja) 2007-12-13 2014-12-10 バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated 嚢胞性線維症膜コンダクタンスレギュレーターのモジュレーター
EP2271622B1 (en) 2008-02-28 2017-10-04 Vertex Pharmaceuticals Incorporated Heteroaryl derivatives as CFTR Modulators
PT2615085E (pt) 2008-03-31 2015-10-09 Vertex Pharma Derivados piridilo como moduladores cftr
JP5575768B2 (ja) 2008-08-13 2014-08-20 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 薬学的組成物およびその投与
US20100256184A1 (en) 2008-08-13 2010-10-07 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administrations thereof
CN102164587A (zh) 2008-09-29 2011-08-24 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)苯甲酸的剂量单元
US20110257223A1 (en) 2008-10-23 2011-10-20 Vertex Pharmaceuticals Incorporated Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
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
JP5645835B2 (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 N−(4−(7−アザビシクロ[2.2.1]ヘプタン−7−イル)−2−(トリフルオロメチル)フェニル)−4−オキソ−5−(トリフルオロメチル)−1,4−ジヒドロキノリン−3−カルボキサミドの固体形態
EA018891B1 (ru) 2008-10-23 2013-11-29 Вертекс Фармасьютикалз, Инкорпорейтед Модуляторы регулятора трансмембранной проводимости при муковисцидозе
EP2382197B1 (en) 2008-12-30 2016-10-05 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
CA2755969C (en) 2009-03-20 2018-05-08 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
SG10201504084QA (en) 2009-03-20 2015-06-29 Vertex Pharma Process for making modulators of cystic fibrosis transmembrane conductance regulator
KR20120083416A (ko) 2009-09-17 2012-07-25 버텍스 파마슈티칼스 인코포레이티드 아자비시클릭 화합물의 제조 방법
EP2490687A1 (en) 2009-10-22 2012-08-29 Vertex Pharmaceuticals Incorporated Compositions for treatment of cystic fibrosis and other chronic diseases
CN102648182A (zh) 2009-10-23 2012-08-22 沃泰克斯药物股份有限公司 用于制备囊性纤维化跨膜传导调节因子的调节剂的方法
CA2778493A1 (en) 2009-10-23 2011-04-28 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
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
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
PT2826776T (pt) 2010-03-25 2021-02-01 Vertex Pharma Forma amorfa sólida de (r)-1(2,2-difluorobenzo(d)(1,3)dioxol-5-ilo)-n-(1-(2,3-dihidroxipropilo)-6-fluoro-2-(1-hidroxi-2-metilpropan-2-ilo)-1h-indol-5-ilo)-ciclopropanocarboxamida
DK3150198T3 (da) 2010-04-07 2021-11-01 Vertex Pharma Farmaceutiske sammensætninger af 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioxol-5-yl)-cyclopropancarboxamido)-3-methylpyriodin-2-yl)benzoesyre og indgivelse deraf
BR112012026257A2 (pt) 2010-04-07 2017-03-14 Vertex Pharma formas sólidas de ácido 3-(6-(1-(2-,2-difluorbenzo[d][1,3]dioxol-5-il)ciclopropanocarboxamido)-3-metilpiridin-2-il)benzóico
EP2560651A1 (en) 2010-04-22 2013-02-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
NZ603043A (en) 2010-04-22 2015-02-27 Vertex Pharma Pharmaceutical compositions comprising cftr modulators and administrations thereof
MX2012012204A (es) 2010-04-22 2012-12-05 Vertex Pharma Proceso para producir compuestos de cicloalquilcarboxamido-indol.
EP2560649A1 (en) 2010-04-22 2013-02-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
AU2011255237A1 (en) 2010-05-20 2012-11-29 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
US8404849B2 (en) 2010-05-20 2013-03-26 Vertex Pharmaceuticals 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
MX2013002035A (es) 2010-08-23 2013-03-25 Vertex Pharma Composiciones farmaceuticas de (r)-1-(2, 2-difluorobenzo[d] [1, 3]dioxol-5-il)-n-(1-(2, 3-dihidroxipropil)-6-fluoro-2-(1-hidroxi-2 -metilpropano-2-il)-1h-indol-5-il) ciclopropanocarboxamida y administracion de las mismas.
RU2013113627A (ru) 2010-08-27 2014-10-10 Вертекс Фармасьютикалз Инкорпорейтед Фармацевтическая композиция и ее введения
US8802700B2 (en) 2010-12-10 2014-08-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
ME02650B (me) 2011-11-08 2017-06-20 Vertex Pharma Modulatori atp- vezujućih kasetnih transportera
CA2862859C (en) 2012-01-25 2022-08-02 Vertex Pharmaceuticals Incorporated Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid
US20130217020A1 (en) 2012-02-22 2013-08-22 National Health Research Institutes Methods for improving sensitivity and specificity of screening assays of kras codons 12 and 13 mutations
CN109966264A (zh) 2012-02-27 2019-07-05 沃泰克斯药物股份有限公司 药物组合物及其施用
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

Also Published As

Publication number Publication date
WO2009123896A1 (en) 2009-10-08
NZ600772A (en) 2013-10-25
CN101981011B (zh) 2014-05-07
EP2271621A1 (en) 2011-01-12
US8524910B2 (en) 2013-09-03
HK1219729A1 (zh) 2017-04-13
JP2014080436A (ja) 2014-05-08
US20090246137A1 (en) 2009-10-01
HK1198537A1 (en) 2015-05-15
JP5622285B2 (ja) 2014-11-12
EP2271621B1 (en) 2013-11-20
US20120270869A1 (en) 2012-10-25
ES2442945T3 (es) 2014-02-14
ES2552990T3 (es) 2015-12-03
EP2980077A1 (en) 2016-02-03
PL2615085T3 (pl) 2016-02-29
CN103951614A (zh) 2014-07-30
AU2009231993B2 (en) 2013-10-10
EP2615085A1 (en) 2013-07-17
EP2615085B1 (en) 2015-08-26
SI2615085T1 (sl) 2015-11-30
JP5930487B2 (ja) 2016-06-08
US8889875B2 (en) 2014-11-18
NZ616097A (en) 2015-04-24
JP2011516420A (ja) 2011-05-26
NZ588006A (en) 2012-08-31
CA2718310A1 (en) 2009-10-08
PT2615085E (pt) 2015-10-09
DK2615085T3 (en) 2015-10-05
JP2015131860A (ja) 2015-07-23
HUE026220T2 (en) 2016-05-30
US8227615B2 (en) 2012-07-24
US20130317020A1 (en) 2013-11-28
EP2980077B1 (en) 2020-05-06
CA2718310C (en) 2018-08-07
CN101981011A (zh) 2011-02-23
AU2009231993A1 (en) 2009-10-08
CY1116953T1 (el) 2017-04-05

Similar Documents

Publication Publication Date Title
HRP20151141T1 (hr) Derivati piridila kao modulatori cftr
HRP20170458T1 (hr) Modulatori atp - vezujućih kasetnih transportera
HRP20150288T1 (hr) Modulatori atp-vezujuä†ih kasetnih transportera
HRP20170847T1 (hr) Modulatori atp - vezujućih kasetnih transportera
RU2008118001A (ru) Модуляторы атф-зависимых транспортеров
JP2011513321A5 (hr)
HRP20210165T1 (hr) Čvrsta disperzija amorfnog oblika (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
JP2011516420A5 (hr)
JP2011505338A5 (hr)
SI3091011T1 (en) Modulators of ATP conveyor belt conveyors
RU2011122646A (ru) Модуляторы переносчиков атф-связывающих кассет
NZ746793A (en) Silicone atoms containing ivacaftor analogues
NZ587545A (en) Heteroaryl derivatives as cftr modulators
JP2007504255A5 (hr)
NZ581259A (en) Modulators of cystic fibrosis transmembrane conductance regulator
RU2006120549A (ru) Тиазолы и оксазолы, применяемые в качестве модуляторов транспортеров арт-связывающей кассеты
HRP20160682T1 (hr) Čvrsti oblici 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioksol-5-il)ciklopropankarboksiamido)-3-metilpiridin-2-il)benzojeve kiseline
JP2007519740A5 (hr)
JP2009521468A5 (hr)
RU2009120976A (ru) Производные азаиндола в качестве модуляторов cftr
ES2683633T3 (es) Moduladores de regulador de conductancia transmembrana de la fibrosis quística
HRP20140695T1 (hr) Modulatori cistiäśno-fibroznog transmembranskog regulatora provodljivosti
NZ732701A (en) Compounds, compositions, and methods for increasing cftr activity
ES2628465T3 (es) Derivados deuterados de ivacaftor
JP2007509044A5 (hr)