AR078408A1 - Derivados de indol como moduladores de los crac - Google Patents

Derivados de indol como moduladores de los crac

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Publication number
AR078408A1
AR078408A1 ARP100103446A ARP100103446A AR078408A1 AR 078408 A1 AR078408 A1 AR 078408A1 AR P100103446 A ARP100103446 A AR P100103446A AR P100103446 A ARP100103446 A AR P100103446A AR 078408 A1 AR078408 A1 AR 078408A1
Authority
AR
Argentina
Prior art keywords
alkyl
alkoxy
optionally substituted
phenyl
carbonyl
Prior art date
Application number
ARP100103446A
Other languages
English (en)
Inventor
Muzaffar Alam
Wylie Solang Palmer
Tania Silva
Robert Stephen Wilhelm
Ronald Charles Hawley
Joshua Kennedy-Smith
Ana Elena Minatti
Bois Daisy Joe Du
Original Assignee
Hoffmann La Roche
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Filing date
Publication date
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of AR078408A1 publication Critical patent/AR078408A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Abstract

Se describen también métodos de obtencion de los compuestos y el uso de los compuestos para el tratamiento de enfermedades asociadas con los canales de calcio activados con la liberacion de calcio (CRAC). Reivindicacion 1: Un compuesto de la formula (1): en la que: R1 es: - fenilo sustituido una, dos o tres veces por un grupo o grupo elegidos con independencia entre: alquilo C1-6; alcoxi C1-6; halogeno; halo-alquilo C1-6; halo-alcoxi C1-6; nitrilo; acetilo; (alcoxi C1-6)-carbonilo; aminocarbonilo; aminosulfonilo; (alquil C1-6)-carbonilamino; (alquil C1-6)-sulfanilo; (alquil C1-6)-sulfonilo; (alcoxi C1-6)-alquilo C1-6; hidroxi-alquilo C1-6; amino; hidroxi; sulfonilmorfolina; sulfonilmetilpiperazina; heterociclilo; fenilo que puede estar opcionalmente sustituido; o heteroarilo que puede estar opcionalmente sustituido; - piridinilo opcionalmente sustituido una o dos veces por un grupo o grupos elegidos con independencia entre: alquilo C1-6; alcoxi C1-6; halogeno; halo-alquilo C1-6 nitrilo; acetilo; (alcoxi C1-6)-carbonilo; (alquil C1-6)-carbonilamino; (alquil C1-6)-sulfanilo; (alquil C1-6)-sulfonilo; (alcoxi C1-6)-alquilo C1-6; hidroxi-alquilo C1-6; amino; oxo; hidroxi; heterociclilo; fenilo que puede estar opcionalmente sustituido; o heteroarilo que puede estar opcionalmente sustituido; - pirimidinilo opcionalmente sustituido una o dos veces por un grupo o grupos elegidos con independencia entre: alquilo C1-6; alcoxi C1-6; halogeno; halo-alquilo C1-6; nitrilo; acetilo; (alcoxi C1-6)-carbonilo; (alquil C1-6)-carbonilamino; (alquil C1-6)-sulfanilo; (alquil C1-6)-sulfonilo; (alcoxi C1-6)-alquilo C1-6; hidroxi-alquilo C1-6; amino; oxo; hidroxi; heterociclilo; fenilo que puede estar opcionalmente sustituido; o heteroarilo que puede estar opcionalmente sustituido; o - un anillo heteroarilo de cinco eslabones opcionalmente sustituido una, dos o tres veces por un grupo o grupos elegidos con independencia entre: alquilo C1-6; cicloalquilo C3-6; alcoxi C1-6; halogeno; halo-alquilo C1-6; nitrilo; acetilo; (alcoxi C1-6)-carbonilo; (alquil C1-6)-carbonilamino; (alquil C1-6)-sulfanilo; (alquil C1-6)-sulfonilo; (alcoxi C1-6)-alquilo C1-6; hidroxi-alquilo C1-6; amino; oxo; hidroxi; heterociclilo; fenilo que puede estar opcionalmente sustituido; y heteroarilo que puede estar opcionalmente sustituido; o dos de dichos sustituyentes junto con los átomos a los que están unidos pueden formar un fenilo fusionado con el anillo heteroarilo de cinco eslabones; es: - cicloalquilo C3-6; - fenilo sustituido una, dos o tres veces por un grupo o grupos elegidos con independencia entre: alquilo C1-6; alcoxi C1-6; alcoxihidroxi C1-6; halogeno; halo-alquilo C1-6; haloalcoxi C1-6; nitrilo; acetilo; (alcoxi C1-6)-carbonilo; (alquil C1-6)-carbonilamino; (alquil C1-6)-sulfanilo; (alquil C1-6)-sulfonilo; (alcoxi C1-6)-alquilo C1-6; hidroxi-alquilo C1-6; (alquil C1-6)-carbonilhidroxi; (alcoxi C1-6)-ciano; amino; hidroxi; fenilo que puede estar opcionalmente sustituido; o heteroarilo que puede estar opcionalmente sustituido; - piridinilo opcionalmente sustituido una o dos veces por un grupo o grupos elegidos con independencia entre: alquilo C1-6; alcoxi C1-6; halogeno; halo-alquilo C1-6; nitrilo; acetilo; (alcoxi C1-6)-carbonilo; (alquil C1-6)-carbonil- amino; (alquil C1-6)-sulfanilo; (alquil C1-6)-sulfonilo; (alcoxi C1-6)-alquilo C1-6; hidroxi-alquilo C1-6; amino; oxo; hidroxi; fenilo que puede estar opcionalmente sustituido; o heteroarilo que puede estar opcionalmente sustituido; - pirimidinilo opcionalmente sustituido una o dos veces por un grupo o grupos elegidos con independencia entre: alquilo C1-6; alcoxi C1-6; halogeno; halo-alquilo C1-6; nitrilo; acetilo; (alcoxi C1-6)-carbonilo; (alquil C1-6)-carbonilamino; (alquil C1-6)-sulfanilo; (alquil C1-6)-sulfonilo; (alcoxi C1-6)-alquilo C1-6; hidroxi-alquilo C1-6; fenilo que puede estar opcionalmente sustituido; o heteroarilo que puede estar opcionalmente sustituido; o - un anillo heteroarilo de cinco eslabones opcionalmente sustituido una o dos veces por un grupo o grupos elegidos con independencia entre: alquilo C1-6; alcoxi C1-6; halogeno; halo-alquilo C1-6; cicloalquilo C3-6; halo-alcoxi C1-6; nitrilo; acetilo; (alcoxi C1-6)-carbonilo; (alquil C1-6)-carbonilamino; (alquil C1-6)-sulfanilo; (alquil C1-6)-sulfonilo; (alcoxi C1-6)-alquilo C1-6; hidroxi-alquilo C1-6; amino; oxo; hidroxi; fenilo que puede estar opcionalmente sustituido; y heteroarilo que puede estar opcionalmente sustituido; o dos de dichos sustituyentes junto con los átomos a los que están unidos pueden formar un fenilo fusionado con dicho anillo heteroarilo de cinco eslabones; R3 es hidrogeno; R3' es hidrogeno o alquilo C1-6; es un numero de 0 a 3; cada R4 se elige con independencia entre: hidrogeno; alquilo C1-6; alcoxi C1-6; halogeno; y halo-alquilo C1-6, y dicha línea discontinua es un enlace o está ausente, o una sal farmacéuticamente aceptable de los mismos.
ARP100103446A 2009-09-24 2010-09-22 Derivados de indol como moduladores de los crac AR078408A1 (es)

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US37806210P 2010-08-30 2010-08-30

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US (1) US20110071150A1 (es)
EP (1) EP2480529A1 (es)
JP (2) JP2013505913A (es)
KR (1) KR20120068947A (es)
CN (1) CN102574788A (es)
AR (1) AR078408A1 (es)
BR (1) BR112012006630A2 (es)
CA (1) CA2771026A1 (es)
MX (1) MX2012003539A (es)
RU (1) RU2012116207A (es)
TW (1) TW201121952A (es)
WO (1) WO2011036130A1 (es)

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CA2771026A1 (en) 2011-03-31
JP2013505913A (ja) 2013-02-21
US20110071150A1 (en) 2011-03-24
JP2012246302A (ja) 2012-12-13
MX2012003539A (es) 2012-04-30
EP2480529A1 (en) 2012-08-01
TW201121952A (en) 2011-07-01
RU2012116207A (ru) 2013-10-27
BR112012006630A2 (pt) 2016-05-03
CN102574788A (zh) 2012-07-11
WO2011036130A1 (en) 2011-03-31
KR20120068947A (ko) 2012-06-27

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