AR124090A1 - MODULATORS OF THE REGULATOR OF TRANSMEMBRANE CONDUCTANCE IN CYSTIC FIBROSIS - Google Patents
MODULATORS OF THE REGULATOR OF TRANSMEMBRANE CONDUCTANCE IN CYSTIC FIBROSISInfo
- Publication number
- AR124090A1 AR124090A1 ARP210103184A ARP210103184A AR124090A1 AR 124090 A1 AR124090 A1 AR 124090A1 AR P210103184 A ARP210103184 A AR P210103184A AR P210103184 A ARP210103184 A AR P210103184A AR 124090 A1 AR124090 A1 AR 124090A1
- Authority
- AR
- Argentina
- Prior art keywords
- independently selected
- optionally substituted
- alkyl
- cycloalkyl
- halogen
- Prior art date
Links
- 201000003883 Cystic fibrosis Diseases 0.000 title abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 20
- 229910052736 halogen Inorganic materials 0.000 abstract 16
- 150000002367 halogens Chemical class 0.000 abstract 16
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 12
- 125000000041 C6-C10 aryl group Chemical group 0.000 abstract 12
- 150000001875 compounds Chemical class 0.000 abstract 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 8
- 125000000623 heterocyclic group Chemical group 0.000 abstract 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 6
- 125000004043 oxo group Chemical group O=* 0.000 abstract 6
- 229910052739 hydrogen Inorganic materials 0.000 abstract 5
- 239000001257 hydrogen Substances 0.000 abstract 5
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 abstract 4
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 abstract 4
- 125000004429 atom Chemical group 0.000 abstract 3
- 150000002431 hydrogen Chemical class 0.000 abstract 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract 3
- 150000003839 salts Chemical class 0.000 abstract 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 abstract 2
- -1 -ORX2 and -N(RX2)2) Chemical group 0.000 abstract 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- 102000012605 Cystic Fibrosis Transmembrane Conductance Regulator Human genes 0.000 abstract 2
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 2
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 abstract 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 abstract 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 239000003937 drug carrier Substances 0.000 abstract 1
- 125000004428 fluoroalkoxy group Chemical group 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero 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
- A61K31/40—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
- A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/529—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains four or more hetero rings
-
- 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
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
La descripción proporciona moduladores del regulador de la conductancia transmembrana de la fibrosis quística (CFTR), composiciones farmacéuticas que contienen al menos uno de tales moduladores, métodos para tratar la fibrosis quística mediante el uso de tales moduladores y composiciones farmacéuticas y procesos para elaborar tales moduladores. Reivindicación 1: Un compuesto que se selecciona de los compuestos de la fórmula (1), y derivados deuterados y sales farmacéuticamente aceptables de estos, donde: X se selecciona de -N(RX¹)- y un resto de fórmula (2); el Anillo A es un heterociclilo de 6 a 4 miembros sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de alquilo C₁-C₆ y oxo; RX¹ se selecciona de H, alquilo C₁-C₆ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de hidroxi, oxo, -ORX² y -N(RX²)₂), y cicloalquilo C₃-C₈; cada RX² se selecciona independientemente de H y alquilo C₁-C₆; cada Y se selecciona independientemente de -C(RY)₂-, -O-, -CO-, -NRYN-, y un resto de fórmula (3), donde cada RYN se selecciona independientemente de H, alquilo C₁-C₄ y CO₂RYN¹, donde cada RYN¹ se selecciona independientemente de alquilo C₁-C₄ y cicloalquilo C₃-C₆; cada RY se selecciona independientemente de hidrógeno, hidroxi, halógeno, alquilo C₁-C₆ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de hidroxi, alcoxi C₁-C₆ y Q), cicloalquilo C₃-C₈, arilo C₆-C₁₀ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de halógeno), heteroarilo de 5 a 10 miembros, -ORY¹, -CO₂RY¹, -CORY¹, -CON(RY¹)₂ y -N(RY¹)₂; o dos RY del mismo átomo se toman en conjunto para formar un anillo que se selecciona de cicloalquilo C₃-C₈ y heterociclilo de 3 a 7 miembros; o dos RY, uno de los cuales se encuentra en un átomo y el segundo de los cuales se encuentra en un átomo adyacente, se toman en conjunto para formar un enlace pi; cada RY¹ se selecciona independientemente de hidrógeno y alquilo C₁-C₆, o dos RY¹ unidos al mismo nitrógeno que se toman en conjunto forman un heterociclilo de 3 a 6 miembros; el Anillo B se selecciona de: arilo C₆-C₁₀ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de halógeno, alquilo C₁-C₆ y alcoxi C₁-C₆), cicloalquilo C₃-C₈, heteroarilo de 5 a 10 miembros y heterociclilo de 3 a 6 miembros (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de alquilo C₁-C₆); cada Q se selecciona independientemente de: alquilo C₁-C₆ sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de: halógeno, oxo, arilo C₆-C₁₀ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de halógeno y -OCF₃) y cicloalquilo C₃-C₈, cicloalquilo C₃-C₈ sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de: halógeno, CN, alquilo C₁-C₆ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de halógeno -NH₂ y -NHCOMe), alcoxi C₁-C₆, arilo C₆-C₁₀ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de alquilo C₁-C₆) y cicloalquilo C₃-C₈, arilo C₆-C₁₀ sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de: halógeno, CN, alquilo C₁-C₆ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de halógeno e hidroxi), alcoxi C₁-C₆ sustituido opcionalmente con 1 - 4 grupos que se seleccionan independientemente de: halógeno, cicloalquilo C₃-C₈ (sustituido opcionalmente con CF₃), cicloalquilo C₃-C₈ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de halógeno, CF₃, OCF₃ y alquilo C₁-C₆) y arilo C₆-C₁₀, heteroarilo de 5 a 10 miembros sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de: halógeno, alquilo C₁-C₆ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de halógeno), cicloalquilo C₃-C₈ (sustituido opcionalmente con 1 - 3 grupos CF₃) y heterociclilo de 3 a 10 miembros, heterociclilo de 3 a 10 miembros sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de: alquilo C₁-C₆ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de oxo y cicloalquilo C₃-C₈) y oxo; cada R¹ se selecciona independientemente de halógeno, fluoroalquilo C₁-C₆, alquilo C₁-C₆ (sustituido opcionalmente con un grupo que se selecciona de hidroxi, arilo C₆-C₁₀ y heteroarilo de 6 a 5 miembros), -OR², -N(R²)₂, -CO₂R², -CO-N(R²)₂, -CN, cicloalquilo C₃-C₈, arilo C₆-C₁₀, heteroarilo de 5 a 6 miembros (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de alquilo C₁-C₆), heterociclilo de 3 a 6 miembros, - B(OR²)₂, -SO₂R², -SR², -SOR², -PO(OR²)₂ y -PO(R²)₂; cada R² se selecciona independientemente de hidrógeno, alquilo C₁-C₆ (sustituido opcionalmente con 1 - 6 grupos que se seleccionan independientemente de halógeno), fluoroalquilo C₁-C₆ y arilo C₆-C₁₀ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de fluoroalquilo C₁-C₆ y fluoroalcoxi C₁-C₆); Z se selecciona de los compuestos del grupo de fórmulas (4); donde el Anillo C se selecciona de arilo C₆-C₁₀ y heteroarilo de 5 a 10 miembros; RZ¹ se selecciona de hidrógeno, -CN, alquilo C₁-C₆ (sustituido opcionalmente con 1 - 3 hidroxi), fluoroalquilo C₁-C₆, heterociclilo de 3 a 6 miembros, cicloalquilo C₃-C₆, arilo C₆-C₁₀ y heteroarilo de 5 a 6 miembros; RZ² se selecciona de hidrógeno, halógeno, hidroxi, NH₂, NH(CO)(alquilo C₁-C₆) y alcoxi C₁-C₆ (sustituido opcionalmente con 1 - 3 grupos que se seleccionan independientemente de cicloalquilo C₃-C₁₀), o RZ¹ y RZ², tomados en conjunto, forman un grupo que se selecciona de oxo y =N-OH; cada RZ³ se selecciona independientemente de hidroxi, alcoxi C₁-C₆, alquilo C₁-C₆ y arilo C₆-C₁₀; o dos RZ³ se toman en conjunto para formar un heterociclilo de 3 a 6 miembros; n se selecciona de 4, 5, 6, 7 y 8; y m se selecciona de 0, 1, 2 y 3. Reivindicación 28: Un compuesto seleccionado de los compuestos de la Tabla 10, sales farmacéuticamente aceptables de estos y derivados deuterados de cualquiera de los anteriores. Reivindicación 29: Un compuesto de acuerdo con la reivindicación 28, donde el compuesto se selecciona de: Tabla (A). Reivindicación 30: Una composición farmacéutica que comprende un compuesto, sal o derivado deuterado de cualquiera de las reivindicaciones 1 a 29 y un portador farmacéuticamente aceptable.The disclosure provides cystic fibrosis transmembrane conductance regulator (CFTR) modulators, pharmaceutical compositions containing at least one such modulator, methods of treating cystic fibrosis using such modulators, and pharmaceutical compositions and processes for making such modulators. . Claim 1: A compound selected from compounds of formula (1), and deuterated derivatives and pharmaceutically acceptable salts thereof, where: X is selected from -N(RX¹)- and a moiety of formula (2); Ring A is a 6 to 4 membered heterocyclyl optionally substituted with 1-3 groups independently selected from C₁-C₆ alkyl and oxo; RX¹ is selected from H, C₁-C₆ alkyl (optionally substituted with 1-3 groups independently selected from hydroxy, oxo, -ORX² and -N(RX²)₂), and C₃-C₈ cycloalkyl; each RX² is independently selected from H and C₁-C₆ alkyl; each Y is independently selected from -C(RY)₂-, -O-, -CO-, -NRYN-, and a moiety of formula (3), where each RYN is independently selected from H, C₁-C₄ alkyl, and CO₂RYN¹ , where each RYN¹ is independently selected from C₁-C₄ alkyl and C₃-C₆ cycloalkyl; each RY is independently selected from hydrogen, hydroxy, halogen, C₁-C₆ alkyl (optionally substituted with 1-3 groups independently selected from hydroxy, C₁-C₆ alkoxy, and Q), C₃-C₈ cycloalkyl, C₆-C₁₀ aryl (substituted optionally with 1-3 groups which are independently selected from halogen), 5- to 10-membered heteroaryl, -ORY¹, -CO₂RY¹, -CORY¹, -CON(RY¹)₂ and -N(RY¹)₂; or two RY's of the same atom are taken together to form a ring selected from C₃-C₈ cycloalkyl and 3 to 7 membered heterocyclyl; or two RY's, one of which is on one atom and the second of which is on an adjacent atom, are taken together to form a pi bond; each RY¹ is independently selected from hydrogen and C₁-C₆ alkyl, or two RY¹ attached to the same nitrogen taken together form a 3- to 6-membered heterocyclyl; Ring B is selected from: C₆-C₁₀ aryl (optionally substituted with 1-3 groups independently selected from halogen, C₁-C₆ alkyl, and C₁-C₆ alkoxy), C₃-C₈ cycloalkyl, 5- to 10-membered heteroaryl, and heterocyclyl 3-6 membered (optionally substituted with 1-3 groups independently selected from C₁-C₆ alkyl); each Q is independently selected from: C₁-C₆ alkyl optionally substituted with 1-3 groups independently selected from: halogen, oxo, C₆-C₁₀ aryl (optionally substituted with 1-3 groups independently selected from halogen and -OCF₃) and C₃-C₈ cycloalkyl, C₃-C₈ cycloalkyl optionally substituted with 1-3 groups independently selected from: halogen, CN, C₁-C₆ alkyl (optionally substituted with 1-3 groups independently selected from halogen -NH₂ and -NHCOMe ), C₁-C₆ alkoxy, C₆-C₁₀ aryl (optionally substituted with 1-3 groups independently selected from C₁-C₆ alkyl) and C₃-C₈ cycloalkyl, C₆-C₁₀ aryl optionally substituted with 1-3 independently selected groups of: halogen, CN, C₁-C₆ alkyl (optionally substituted with 1-3 groups independently selected from halogen and hydroxy), C₁-C₆ alkoxy optionally substituted with 1-4 groups independently selected from: halogen, C₃-cycloalkyl C₈ (optionally substituted with CF₃), C₃-C₈ cycloalkyl (optionally substituted with 1-3 groups independently selected from halogen, CF₃, OCF₃ and C₁-C₆ alkyl) and C₆-C₁₀ aryl, optionally substituted 5-10 membered heteroaryl with 1-3 groups independently selected from: halogen, C₁-C₆ alkyl (optionally substituted with 1-3 groups independently selected from halogen), C₃-C₈ cycloalkyl (optionally substituted with 1-3 CF₃ groups), and C₃-C₈ cycloalkyl 3-10 membered, 3-10 membered heterocyclyl optionally substituted with 1-3 groups independently selected from: C₁-C₆ alkyl (optionally substituted with 1-3 groups independently selected from oxo and C₃-C₈ cycloalkyl) and oxo ; each R¹ is independently selected from halogen, C₁-C₆ fluoroalkyl, C₁-C₆ alkyl (optionally substituted with a group selected from hydroxy, C₆-C₁₀ aryl, and 6- to 5-membered heteroaryl), -OR², -N(R²) ₂, -CO₂R², -CO-N(R²)₂, -CN, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 5- to 6-membered heteroaryl (optionally substituted with 1-3 groups independently selected from C₁-C₆ alkyl ), 3 to 6 membered heterocyclyl, -B(OR²)₂, -SO₂R², -SR², -SOR², -PO(OR²)₂ and -PO(R²)₂; each R² is independently selected from hydrogen, C₁-C₆ alkyl (optionally substituted with 1-6 groups independently selected from halogen), C₁-C₆ fluoroalkyl, and C₆-C₁₀ aryl (optionally substituted with 1-3 groups independently selected from C₁-C₆ fluoroalkyl and C₁-C₆ fluoroalkoxy); Z is selected from the compounds of the group of formulas (4); where Ring C is selected from C₆-C₁₀ aryl and 5 to 10 membered heteroaryl; RZ¹ is selected from hydrogen, -CN, C₁-C₆ alkyl (optionally substituted with 1-3 hydroxy), C₁-C₆ fluoroalkyl, 3- to 6-membered heterocyclyl, C₃-C₆ cycloalkyl, C₆-C₁₀ aryl, and 5- to 6-membered heteroaryl members; RZ² is selected from hydrogen, halogen, hydroxy, NH₂, NH(CO)(C₁-C₆ alkyl) and C₁-C₆ alkoxy (optionally substituted with 1-3 groups independently selected from C₃-C₁₀ cycloalkyl), or RZ¹ and RZ² , taken together, form a group selected from oxo and =N-OH; each RZ³ is independently selected from hydroxy, C₁-C₆ alkoxy, C₁-C₆ alkyl, and C₆-C₁₀ aryl; or two RZ³ are taken together to form a 3 to 6 membered heterocyclyl; n is selected from 4, 5, 6, 7, and 8; and m is selected from 0, 1, 2, and 3. Claim 28: A compound selected from the compounds in Table 10, pharmaceutically acceptable salts thereof, and deuterated derivatives of any of the foregoing. Claim 29: A compound according to claim 28, wherein the compound is selected from: Table (A). Claim 30: A pharmaceutical composition comprising a compound, salt or deuterated derivative of any of claims 1 to 29 and a pharmaceutically acceptable carrier.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063115552P | 2020-11-18 | 2020-11-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR124090A1 true AR124090A1 (en) | 2023-02-15 |
Family
ID=79602287
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP210103184A AR124090A1 (en) | 2020-11-18 | 2021-11-18 | MODULATORS OF THE REGULATOR OF TRANSMEMBRANE CONDUCTANCE IN CYSTIC FIBROSIS |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP4247817A1 (en) |
| JP (1) | JP2023549547A (en) |
| KR (1) | KR20230123522A (en) |
| CN (1) | CN116670140A (en) |
| AR (1) | AR124090A1 (en) |
| AU (1) | AU2021383176A1 (en) |
| CA (1) | CA3201793A1 (en) |
| CL (1) | CL2023001398A1 (en) |
| CO (1) | CO2023007896A2 (en) |
| CR (1) | CR20230260A (en) |
| DO (1) | DOP2023000099A (en) |
| EC (1) | ECSP23045439A (en) |
| IL (1) | IL302873A (en) |
| MX (1) | MX2023005721A (en) |
| PE (1) | PE20231380A1 (en) |
| WO (1) | WO2022109573A1 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW202333699A (en) * | 2022-02-03 | 2023-09-01 | 美商維泰克斯製藥公司 | Methods of treatment for cystic fibrosis |
| AU2023218262A1 (en) * | 2022-02-08 | 2024-08-22 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| WO2023224931A1 (en) * | 2022-05-16 | 2023-11-23 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| WO2023224924A1 (en) | 2022-05-16 | 2023-11-23 | Vertex Pharmaceuticals Incorporated | Solid forms of a macrocyclic compounds as cftr modulators and their preparation |
| WO2024054851A1 (en) * | 2022-09-07 | 2024-03-14 | Sionna Therapeutics | Macrocyclic compounds, compositions and methods of using thereof |
| WO2024056798A1 (en) | 2022-09-15 | 2024-03-21 | Idorsia Pharmaceuticals Ltd | Macrocyclic cftr modulators |
| TW202421102A (en) | 2022-09-15 | 2024-06-01 | 瑞士商愛杜西亞製藥有限公司 | Combination of macrocyclic cftr modulators with cftr correctors and/or cftr potentiators |
| WO2024056779A1 (en) | 2022-09-15 | 2024-03-21 | Idorsia Pharmaceuticals Ltd | Crystalline form of (3s,7s,10r,13r)-13-benzyl-20-fluoro-7-isobutyl-n-(2-(3-methoxy-1,2,4-oxadiazol-5-yl)ethyl)-6,9-dimethyl-1,5,8,11-tetraoxo-10-(2,2,2-trifluoroethyl)-1,2,3,4,5,6,7,8,9,10,11,12,13,14-tetradecahydro-[1]oxa[4,7,10,14]tetraazacycloheptadecino[16,17-f]quinoline-3-carboxamide |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2558457T3 (en) * | 2011-09-16 | 2016-02-04 | Novartis Ag | Heterocyclic compounds for the treatment of cystic fibrosis |
| US11066417B2 (en) * | 2018-02-15 | 2021-07-20 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulators |
-
2021
- 2021-11-17 CR CR20230260A patent/CR20230260A/en unknown
- 2021-11-17 MX MX2023005721A patent/MX2023005721A/en unknown
- 2021-11-17 EP EP21843853.9A patent/EP4247817A1/en active Pending
- 2021-11-17 WO PCT/US2021/072475 patent/WO2022109573A1/en active Application Filing
- 2021-11-17 CA CA3201793A patent/CA3201793A1/en active Pending
- 2021-11-17 JP JP2023529022A patent/JP2023549547A/en active Pending
- 2021-11-17 CN CN202180090910.1A patent/CN116670140A/en active Pending
- 2021-11-17 PE PE2023001653A patent/PE20231380A1/en unknown
- 2021-11-17 AU AU2021383176A patent/AU2021383176A1/en active Pending
- 2021-11-17 KR KR1020237020002A patent/KR20230123522A/en unknown
- 2021-11-17 IL IL302873A patent/IL302873A/en unknown
- 2021-11-18 AR ARP210103184A patent/AR124090A1/en unknown
-
2023
- 2023-05-16 CL CL2023001398A patent/CL2023001398A1/en unknown
- 2023-05-17 DO DO2023000099A patent/DOP2023000099A/en unknown
- 2023-06-16 EC ECSENADI202345439A patent/ECSP23045439A/en unknown
- 2023-06-16 CO CONC2023/0007896A patent/CO2023007896A2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2021383176A1 (en) | 2023-06-22 |
| PE20231380A1 (en) | 2023-09-07 |
| WO2022109573A1 (en) | 2022-05-27 |
| CN116670140A (en) | 2023-08-29 |
| EP4247817A1 (en) | 2023-09-27 |
| CA3201793A1 (en) | 2022-05-27 |
| CL2023001398A1 (en) | 2023-11-24 |
| MX2023005721A (en) | 2023-07-25 |
| DOP2023000099A (en) | 2023-08-15 |
| KR20230123522A (en) | 2023-08-23 |
| IL302873A (en) | 2023-07-01 |
| JP2023549547A (en) | 2023-11-27 |
| CR20230260A (en) | 2023-10-05 |
| CO2023007896A2 (en) | 2023-09-18 |
| ECSP23045439A (en) | 2023-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AR124090A1 (en) | MODULATORS OF THE REGULATOR OF TRANSMEMBRANE CONDUCTANCE IN CYSTIC FIBROSIS | |
| AR123183A1 (en) | MODULATORS OF THE REGULATOR OF TRANSMEMBRANE CONDUCTANCE IN CYSTIC FIBROSIS | |
| AR114254A1 (en) | CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR MODULATORS, PHARMACEUTICAL COMPOSITIONS, TREATMENT METHODS AND PREPARATION PROCESS OF MODULATORS | |
| EA202090658A1 (en) | CAP-DEPENDENT ENDONUCLEASE INHIBITORS | |
| AR110922A1 (en) | HIV INHIBITING COMPOUNDS | |
| AR054035A1 (en) | BENZODIOXAN AND BENZODIOXOLAN DERIVATIVES AND USE OF THE SAME | |
| KR950704304A (en) | Bicyclic heterocyclic containing sulfonamides and sulfonic acid ester derivatives (BICYCLIC HETEROCYCLIC SULFONAMIDE AND SULFONIC ESTER DERIVATIVES) | |
| AR110153A1 (en) | 3-SUBSTITUTED PROPIONIC ACIDS AS INHIBITORS OF INTEGRINE aV | |
| BR9307595A (en) | Compound, process for its preparation, herbicidal composition, and process for severely damaging or exterminating undesirable plants | |
| AR035795A1 (en) | DERIVATIVES OF GLUTARAMIDE REPLACED WITH N-FENPROPILCICLOPENTILO AS INHIBITORS OF THE NEUTRAL ENDOPEPTIDASE ENZYME, USE OF THE SAME, PROCEDURES AND INTERMEDIARIES FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING THESE INHIBITORS | |
| AR126073A1 (en) | N-(HYDROXYALKYL(HETERO)ARYL)TETRAHYDROFURAN CARBOXAMIDES AS SODIUM CHANNEL MODULATORS | |
| AR111808A1 (en) | PIRIMIDINE DERIVATIVES AS PGE2 RECEIVER MODULATORS | |
| CO2022003123A2 (en) | pharmaceutical compounds | |
| AR108387A1 (en) | TETRAHYDROPIRIMIDODIAZEPIN AND DIHYDROPIRIDODIAZEPIN TYPE COMPOUNDS TO TREAT PAIN AND PAIN-RELATED AFFECTIONS | |
| YU4795A (en) | Derivatives of indole which can be used as 5ht agonists, pharmaceutical preparations which contain them and procedures for preparation | |
| AR005338A1 (en) | ACETYDINALKYL DERIVATIVES OF HETEROCYCLES WITH N-SUBSTITUTED NITROGEN OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, A PROCEDURE TO APPEAR THEM, PHARMACEUTICAL COMPOSITIONS, UTILITIES, SALTS AND COMPOSITES | |
| AR123962A1 (en) | INTERLEUKIN-17 INHIBITORS | |
| AR125608A1 (en) | NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND THEIR USES | |
| TR199903310A2 (en) | Aryl carboxylic acid and tetrazole derivatives. | |
| AR126733A1 (en) | NICOTINAMIDE RIPK1 INHIBITORS | |
| AR119378A1 (en) | NANOPARTICLE FORMULATION OF THE BCL-2 INHIBITOR | |
| PE20211071A1 (en) | ISOXAZOLE CARBOXAMIDE COMPOUNDS AND USES OF THEM | |
| AR088202A1 (en) | INHIBITORS OF THE ACTIVITY OF PROTEIN TIROSINA QUINASA | |
| AR125365A1 (en) | 1H-PYRAZOLE DERIVATIVES AS SIGMA LIGANDS | |
| SE8004868L (en) | NEW OXIMETERS, PREPARATION OF THEM AND PHARMACEUTICAL PREPARATIONS CONTAINING SUCH ETHERS |