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AR079984A1 - Compuestos heterociclicos triciclicos, composiciones y su uso en el tratamiento de enfermedades mediadas por la inhibicion de jak1 - Google Patents

Compuestos heterociclicos triciclicos, composiciones y su uso en el tratamiento de enfermedades mediadas por la inhibicion de jak1

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Publication number
AR079984A1
AR079984A1 ARP110100078A ARP110100078A AR079984A1 AR 079984 A1 AR079984 A1 AR 079984A1 AR P110100078 A ARP110100078 A AR P110100078A AR P110100078 A ARP110100078 A AR P110100078A AR 079984 A1 AR079984 A1 AR 079984A1
Authority
AR
Argentina
Prior art keywords
alkylene
alkyl
halogen
oxo
optionally substituted
Prior art date
Application number
ARP110100078A
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English (en)
Inventor
Joseph P Lyssikatos
Peter DRAGOVICH
Hazel Joan Dyke
Paul Gibbons
Stefan Gradl
Emily Hanan
Christopher Hurley
Sharada Shenvi Labadie
Rohan Mendonca
Stuard Ward
Mark Zak
Tony Johnson
Srinivasan Babu
Michael Koehler
Janusz Josef Kulagowski
Bohdan Waskowycz
Rebecca Pulk
Phillippe Bergeron
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of AR079984A1 publication Critical patent/AR079984A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed 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
    • A61K31/435—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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Transplantation (AREA)
  • Pain & Pain Management (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Por consiguiente, los compuestos pueden incorporarse a composiciones farmacéuticamente aceptables y emplearse para el tratamiento de trastornos inmunologicos o hiperproliferativos. Reivindicacion 1: Un compuesto de la formula 1: los estereoisomeros, tautomeros y sales farmacéuticamente aceptables del mismo, en la que: X es N o CR4; Y es N o CR5; R1 está ausente, o es alquilo C1-12, alquenilo C1-12, alquinilo C1-12, cicloalquilo C3-12, arilo C6-14 o heterociclilo de 3-20 eslabones, dicho R1 está opcionalmente sustituido con independencia por halogeno, oxo, -CN, -ORa, -SRa, -NRaRb, alquileno C1-3 o alquilo C1-6 opcionalmente sustituido por oxo, -CN o halogeno; R2 está ausente, o es alquilo C1-6, alquenilo C2-6, alquinilo C2-6, -(alquileno C1-6)-, -(alquenileno C2-6)-, (alquinileno C2-6)-, -(alquileno C0-6)CN, -(alquileno C0-3)- NRa(alquileno C0-3)-, -(alquileno C0-3)O(alquileno C0-3)-, -(alquileno C0-3)C(O) (alquileno C0-3)-, -(alquileno C0-3)- NRaC(O) (alquileno C0-3)-, -(alquileno C0-3)C(O)NRa(alquileno C0-3)-, -(alquileno Co3)C(O)O(alquileno C0-3)-, -(alquileno C0-3)OC(O) (alquileno C0-3)-, -(alquileno C0-3)NRaC(O)-NRb(alquileno C0-3)-, -(alquileno C0-3)OC(O)NRa(alquileno C0-3)-, -(alquileno C0-3)NRaC(O)O(alquileno C0-3)-, -(alquileno C0-3) S (O)1-2 (alquileno C0-3) -, - (alquileno C0-3) NRaS- (O)1-2(alquileno C0-3, - (alquileno C0-3) S (O) 2NRa (alquileno C0-3) - o - (alquileno C0-3) NRaS(O)1-2NRb (alquileno C0-3) -, dichos alquilo, alquenilo, alquinilo, alquileno, alquenileno y alquinileno están opcionalmente sustituidos con independencia por halogeno, oxo, -CN, -ORc, -SRc, -NRcRd o alquilo C1-3 opcionalmente sustituido por halogeno; R3 está ausente, o es hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14 o heterociclilo de 3-20 eslabones, dicho R3 está opcionalmente sustituido con independencia por R6 R4 es hidrogeno, halogeno o alquilo C1-3; R5 es hidrogeno, halogeno, alquilo C1-12, alquenilo C2-12, alquinilo C2-12, -(alquileno C0-3)CN, -(alquileno C0-3)NRaRb, -(alquileno C0-3)ORa, -(alquileno C0-3)SRa, -(alquileno C0-3)- O(O) Ra, -(alquileno C0-3) NRaC(O)Rb, -(alquileno C0-3)C(O)NRaRb, -(alquileno C0-3)C(O)ORa, (alquileno C0-3)OC(O)Ra, -(alquileno C0-3)NRaC(O)NRaRb, -(alquileno C0-3)OC(O)NRaRb, -(alquileno C0-3)NRaC(O)ORb, -(alquileno C0-3)S(O)1-2Ra, -(alquileno C0-3) NRaS(O)1-2Rb, -(alquileno C0-3)S(O)1-2NRaRb, -(alquileno C0-3) NRaS(O)1-2NRaRb, -(alquileno C0-3) -cicloalquilo C3-12, -(alquileno C0-3)-arilo C6-14, -(alquileno C0-3)-heterociclilo de 3-12 eslabones o -(alquileno C0-3)C(O)-heterociclilo de 3-12 eslabones, dichos alquilo, alquenilo, alquinilo, alquileno, cicloalquilo, arilo y heterociclilo están opcionalmente sustituidos con independencia por halogeno, oxo, -(alquileno C0-3)CN, -(alquileno C0-3)ORc, -(alquileno C0-3)NRcRd, -(alquileno C0-3)C(O)Rc, -(alquileno C0-3)C(O)ORc, -(alquileno C0-3) O(O) NRcRd, -(alquileno C0-3) NRcC(O)Rd, -(alquileno C0-3)O-C(O)NRcRd, -(alquileno C0-3)NRcC(O)NRcRd, -(alquileno C0-3)- NRcC(O)ORd, (alquileno C0-3)S(O)0-2Rc, -(alquileno C0-3)-NRcS(O)1-2Rd, -(alquileno C0-3)S(O)1-2NRcRd, -(alquileno C0-3) -NRcS(O)1-2NRcRd o alquilo C1-6 opcionalmente sustituido por oxo, -CN o halogeno; R6 es con independencia oxo, halogeno, -CN, -C(O)Ra, -C(O)ORa, -NRaC(O)Rb, -C(O)NRaRb, -NRaC(O)NRaRb, -OC(O)NRaRb, -NRaC(O)ORb, -S(O)1-2Ra, -NRaS(O)2Rb, -S(O)2NRaRb, -ORa, -SRa, -NRaRb, alquilo C1-6, cicloalquilo C3-6, alquenilo C2-6, alquinilo C2-6, heterociclilo de 3-7 eslabones o arilo C6-14, y dichos alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo y arilo están opcionalmente sustituidos con independencia por halogeno, oxo, -ON, -ORc, -SRc, -NRcRd o alquilo C1-6 opcionalmente sustituido por oxo o halogeno; cada Ra y Rb es con independencia hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, -(alquileno C0-3)- cicloalquilo C3-6, -(alquileno C0-3)-heterociclilo de 3-12 eslabones, -(alquileno C0-3)C(O)-heterociclilo de 3-12 eslabones o -(alquileno C0-3)-arilo C6-14, dichos alquilo, cicloalquilo, heterociclilo y arilo están opcionalmente sustituidos con independencia por halogeno, oxo, -CN, -ORe, -NReRf, -C(O)Rg, -C(O)Org, -C(O)NRgRh, -NRgC(O)Rh, -OC(O)NRgRh -NRgC(O)NRgRh, -NRgC(O)ORh, -S(O)1-2Rg, -NRgS(O)1-2Rh, -S(O)1-2NRgRh, -NRgS-, (O) 1-2NRgRh cicloalquilo C3-6, heterociclilo de 3-6 eslabones, fenilo o alquilo C1-3 opcionalmente sustituido por oxo o halogeno, o junto con el átomo al que están unidos forman un heterociclilo de 3-6 eslabones opcionalmente sustituido por oxo, halogeno, -C(O)-alquilo C1-6 o alquilo C1-6 opcionalmente sustituido por oxo, halogeno, ORg o NRgNRhcada Rc y Rd es con independencia hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, (alquileno C0-3) -cicloalquilo C3-6, -(alquileno C0-3)-heterociclilo de 3-12 eslabones, -(alquileno C0-3)C(O)-heterociclilo de 3-12 eslabones o -(alquileno C0-3)-arilo C6-14, dichos alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo y arilo están opcionalmente sustituidos con independencia por halogeno, oxo, -CN, -ORg, -NRgRh, -C(O)Rg, -C(O)ORg, -C(O)NRgRh, -NRgC(O)Rh, -OC(O)NRgRh, -NRgC(O)NRgRh, -NRgC(O)ORh, -S(O)1-2Rg, -NRgS(O)1-2Rh, -S(O)1-2NRgRh, NRgS(O)1-2NRgRh, cicloalquilo C3-6, heterociclilo de 3-6 eslabones, fenilo o alquilo C1-6 opcionalmente sustituido por oxo o halogeno, o junto con el átomo al que están unidos forman un heterociclilo de 3-6 eslabones opcionalmente sustituido por oxo, halogeno, -C(O)-alquilo C1-6 o alquilo C6 opcionalmente sustituido por oxo o halogeno; y cada Re, Rf, Rg, Rh es con independencia hidrogeno o alquilo C1-6 opcionalmente sustituido por halogeno u oxo.
ARP110100078A 2010-01-12 2011-01-11 Compuestos heterociclicos triciclicos, composiciones y su uso en el tratamiento de enfermedades mediadas por la inhibicion de jak1 AR079984A1 (es)

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US29440410P 2010-01-12 2010-01-12
US36678510P 2010-07-22 2010-07-22

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AR079984A1 true AR079984A1 (es) 2012-03-07

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Country Status (12)

Country Link
US (1) US8461328B2 (es)
EP (1) EP2523957A1 (es)
JP (1) JP2013517220A (es)
KR (1) KR20140015162A (es)
CN (1) CN102712640A (es)
AR (1) AR079984A1 (es)
BR (1) BR112012017269A2 (es)
CA (1) CA2781578A1 (es)
MX (1) MX2012008049A (es)
RU (1) RU2012132278A (es)
TW (1) TW201129565A (es)
WO (1) WO2011086053A1 (es)

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