WO2013106646A3 - Compounds and methods for the inhibition of vcb e3 ubiquitin ligase - Google Patents

Compounds and methods for the inhibition of vcb e3 ubiquitin ligase Download PDF

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Publication number
WO2013106646A3
WO2013106646A3 PCT/US2013/021141 US2013021141W WO2013106646A3 WO 2013106646 A3 WO2013106646 A3 WO 2013106646A3 US 2013021141 W US2013021141 W US 2013021141W WO 2013106646 A3 WO2013106646 A3 WO 2013106646A3
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WIPO (PCT)
Prior art keywords
ischemia
anemia
patient
present
subject
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PCT/US2013/021141
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French (fr)
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WO2013106646A2 (en
Inventor
Craig M. Crews
Dennis BUCKLEY
Alessio CIULLI
William Jorgensen
Peter C. Gareiss
Inge Van MOLLE
Jeffrey GUSTAFSON
Hyun-Seop Tae
Julien MICHEL
Dentin Wade HOYER
Anke G. ROTH
John David Harling
Ian Edward David Smith
Afjal Hussain MIAH
Sebastian Andre CAMPOS
Joelle Le
Original Assignee
Yale University
Glaxosmithkline Intellectual Property Development Limited
Cambridge Enterprise Limited University Of Cambridge
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Application filed by Yale University, Glaxosmithkline Intellectual Property Development Limited, Cambridge Enterprise Limited University Of Cambridge filed Critical Yale University
Publication of WO2013106646A2 publication Critical patent/WO2013106646A2/en
Publication of WO2013106646A3 publication Critical patent/WO2013106646A3/en

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    • 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
    • C07D417/12—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 linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The present invention relates to novel compounds which find utility as modulators, especially inhibitors of VCB E3 Ubiquitin Ligase and as bioactive agents for use as therapeutics for the stimulation of erythropoiesis in a patient or subject including inducement of EPO production in the patient or subject, for the treatment of chronic anemia and ischemia (limits brain injury during episodes of localized anemia, ischemia and/or stroke and damage to cardiovascular tissue during cardiovascular ischemia), as well as enhancing wound healing processes. Pharmaceutical compositions comprising effective amounts of compounds according to the present invention alone or in combination with an additional erythropoieses stimulating agent such as EPO under the tradename procrit or epogen or darbapoietin alfa under the tradename aranesp. Methods of stimulating erythropoiesis in a subject or patient, including increasing the number of red blood cells and/or hematocrit of the patient, treating anemia, including chronic anemia and anemia associated with chronic kidney disease, dialysis, and cancer chemotherapy, ischemia, stroke and damage to cardiovascular tissue during cardiovascular ischemia as well as enhancing wound healing processes and preventing/reducing scarring secondary to healing represent additional aspects of the present invention. Local enhancement of angiogenesis through induction of VEGF including wound healing and reduction of stent occlusion remain additional aspects of the present invention.
PCT/US2013/021141 2012-01-12 2013-01-11 Compounds and methods for the inhibition of vcb e3 ubiquitin ligase WO2013106646A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261585736P 2012-01-12 2012-01-12
US61/585,736 2012-01-12

Publications (2)

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WO2013106646A2 WO2013106646A2 (en) 2013-07-18
WO2013106646A3 true WO2013106646A3 (en) 2013-09-06

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
JP7463308B2 (en) 2015-03-18 2024-04-08 アルビナス・オペレーションズ・インコーポレイテッド Compounds and methods for enhancing degradation of targeted proteins

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