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AR109437A1 - Derivados de n-(piridin-2-il)piridina-sulfonamida y su uso en el tratamiento de enfermedades - Google Patents

Derivados de n-(piridin-2-il)piridina-sulfonamida y su uso en el tratamiento de enfermedades

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Publication number
AR109437A1
AR109437A1 ARP170102384A ARP170102384A AR109437A1 AR 109437 A1 AR109437 A1 AR 109437A1 AR P170102384 A ARP170102384 A AR P170102384A AR P170102384 A ARP170102384 A AR P170102384A AR 109437 A1 AR109437 A1 AR 109437A1
Authority
AR
Argentina
Prior art keywords
alkyl
substituted
alkoxy
nhr11
hydroxy
Prior art date
Application number
ARP170102384A
Other languages
English (en)
Inventor
Ayako Honda
Sejal Patel
Rodrigo A Rodriguez
Dean Paul Phillips
Victor Ivanovich Nikulin
Robert Epple
Bei Chen
Mihai Azimioara
Original Assignee
Novartis Ag
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 Novartis Ag filed Critical Novartis Ag
Publication of AR109437A1 publication Critical patent/AR109437A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/76—Nitrogen atoms to which a second hetero atom is attached
    • 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
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La presente solicitud se relaciona con compuestos capaces de modular la actividad de CFTR. Además, un método para fabricar los compuestos, su uso médico, en particular para su uso en el tratamiento y manejo de enfermedades o trastornos incluyendo fibrosis quística y trastornos relacionados. Reivindicación 1: Un compuesto de la fórmula (1), en donde: el anillo A es un anillo de arilo C₆₋₁₀; el anillo B es piridinilo; R¹ y R² son cada uno independientemente hidrógeno, nitrilo, alcoxilo C₁₋₄, alquilo C₁₋₄ halo-sustituido, cicloalquilo C₃₋₆ o alcoxilo C₁₋₄ halo-sustituido; R³ y R⁴ son cada uno independientemente hidrógeno, nitrilo, CD₃, cicloalquilo C₃₋₆, heterociclo C₄₋₆, alcoxilo C₁₋₄, halógeno, alquilo C₁₋₄, alquilo C₁₋₄ halo-sustituido, alquilo C₁₋₄ hidroxi-sustituido o alcoxilo C₁₋₄ halo-sustituido; n es 0, 1 ó 2; R⁵ es -NR⁷R⁸, -OR⁹ o R¹⁰; R⁶ es hidrógeno, hidroxilo, alquilo C₁₋₂, alcoxilo C₁₋₂, alquilo C₁₋₂ hidroxi-sustituido, halógeno o amino; m es 0, 1 ó 2; R⁷ es hidrógeno, alquilo C₁₋₆, cicloalquilo C₃₋₆, un heterociclo de 4 a 7 miembros completa o parcialmente saturado, en donde dicho heterociclo de 4 a 7 miembros es opcionalmente sustituido por 1 a 4 sustituyentes cada uno independientemente seleccionado a partir de halógeno, hidroxilo, alquilo C₁₋₄, alcoxilo C₁₋₄, -alquilo C₁₋₄ halo-sustituido, -alquilo C₁₋₄ hidroxi-sustituido, -alcoxilo C₁₋₄ halo-sustituido, oxo, nitrilo, cicloalquilo C₃₋₆, heterociclo C₄₋₆, NHR¹¹, -C(O)-R¹³, -C(O)NHR¹¹, alquilo C₁₋₃-C(O)NHR¹¹ y -C(O)O-R¹²; R⁸ es hidrógeno o alquilo C₁₋₄; R⁹ es hidrógeno, cicloalquilo C₃₋₆ o un heterociclo de 4 a 7 miembros completamente o parcialmente saturado cada anillo es opcionalmente sustituido por uno a cuatro sustituyentes cada uno independientemente seleccionado a partir de halógeno, hidroxi, alquilo C₁₋₄, alcoxilo C₁₋₄, alquilo C₁₋₄ halo-sustituido, alquilo C₁₋₄ hidroxi-sustituido, alcoxilo C₁₋₄ halo-sustituido, oxo, nitrilo, cicloalquilo C₃₋₆, heterociclo C₄₋₆, NHR¹¹, -C(O)-R¹³, -C(O)NHR¹¹, alquilo C₁₋₃-C(O)NHR¹¹ y -C(O)O-R¹²; R¹⁰ es un heterociclo de 4 a 10 miembros completa o parcialmente saturado opcionalmente sustituido por uno a cuatro sustituyentes cada uno independientemente seleccionado a partir de halógeno, hidroxilo, alquilo C₁₋₄, alcoxilo C₁₋₄, alquilo C₁₋₄ halo-sustituido, alquilo C₁₋₄ hidroxi-sustituido, alcoxilo C₁₋₄ halo-sustituido, oxo, nitrilo, cicloalquilo C₃₋₆, heterociclo C₄₋₆, NHR¹¹, -C(O)-R¹³, -C(O)NHR¹¹, alquilo C₁₋₃-C(O)NHR¹¹, -C(O)-alquilo C₁₋₃-NHR¹¹ y -C(O)O-R¹², en donde dicho cicloalquilo C₃₋₆ y heterociclo C₄₋₆ son opcionalmente sustituidos por 1 a 3 sustituyentes cada uno independientemente seleccionado a partir de hidroxilo, halógeno, amino, alquilo C₁₋₄, alquilo C₁₋₄ halo-sustituido y alquilo C₁₋₄ hidroxi-sustituido; R¹¹ es hidrógeno, alquilo C₁₋₄ o alquilo C₀₋₃-C(O)O-R¹⁴; R¹² es hidrógeno, alquilo C₁₋₄ o alquilo C₁₋₃-C(O)-NHR¹⁴; R¹³ es alquilo C₁₋₄, en donde dicho alquilo es opcionalmente sustituido por amino; y R¹⁴ es hidrógeno o alquilo C₁₋₄; o una sal farmacéuticamente aceptable del mismo.
ARP170102384A 2016-08-29 2017-08-29 Derivados de n-(piridin-2-il)piridina-sulfonamida y su uso en el tratamiento de enfermedades AR109437A1 (es)

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US201662380659P 2016-08-29 2016-08-29

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US (2) US10450273B2 (es)
EP (1) EP3504194B1 (es)
JP (1) JP7035055B2 (es)
KR (1) KR20190040319A (es)
CN (1) CN109641873B (es)
AR (1) AR109437A1 (es)
AU (1) AU2017319430A1 (es)
BR (1) BR112019003883A2 (es)
CA (1) CA3031073A1 (es)
EA (1) EA201990609A1 (es)
ES (1) ES2898069T3 (es)
MX (1) MX2019002439A (es)
TW (1) TW201811766A (es)
UY (1) UY37379A (es)
WO (1) WO2018042316A1 (es)

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KR20230052954A (ko) 2020-08-20 2023-04-20 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 점액 과다분비를 특징으로 하는 호흡기 질환의 치료 방법
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