CA2628193A1 - Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties - Google Patents

Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties Download PDF

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Publication number
CA2628193A1
CA2628193A1 CA002628193A CA2628193A CA2628193A1 CA 2628193 A1 CA2628193 A1 CA 2628193A1 CA 002628193 A CA002628193 A CA 002628193A CA 2628193 A CA2628193 A CA 2628193A CA 2628193 A1 CA2628193 A1 CA 2628193A1
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cells
composition
group
substituted
alkyl
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Granted
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CA002628193A
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French (fr)
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CA2628193C (en
Inventor
Gary D. Glick
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University of Michigan
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Priority to CA2779041A priority Critical patent/CA2779041A1/en
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Classifications

    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Abstract

The present invention relates to novel chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides novel 1,4- benzodiazepine-2,5-dione compounds, and methods of using novel l,4-benzodiazepine-2,5-dione compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, and the like.

Claims (15)

  1. Claim 1. A composition configured to induce apoptosis in a cell, said composition comprising a compound described by a formula selected from the group consisting of:

    ; substituted and unsubstituted, including both R and S enantiomeric forms and racemic mixtures;
    wherein R1 is an electron rich heterocycle;
    wherein R2 is selected from the group consisting of H, alkyl, substituted alkyl, and R1;
    wherein R3 is selected from the group consisting of H, alkyl, and substituted alkyl;
    wherein R4 and R4' is independently selected from the group consisting of CH3, halogen, SO2R4", SO2N(R4")2, OR4", N(R4")2, CON(R4")2, NHCOR4", NHSO2R4', alkyl, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl; wherein R4" is selected from the group consisting of halogen, H, alkyl, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl, aryl, mono-substituted aryl, di-substituted aryl, tri-substituted aryl, cycloalipathic, mono-substituted cycloalipathic, di-substituted cycloalipathic, tri-substituted cycloalipathic.;
    wherein R5 is selected from the group consisting of H, alkyl, mono-substituted aryl, di-substituted aryl, and tri-substituted aryl; and wherein R6 is selected from the group consisting of C, N or S.
  2. Claim 2. The composition of Claim 1, wherein said electron rich heterocycle contains or more heterocyclic atoms.
  3. Claim 3. The composition of Claim 1, wherein R1 is selected from the group consisting of , wherein R1' is selected from the group consisting of cycloalipathic, aryl, substituted aryl, heterocyclic, and substituted heterocyclic.
  4. Claim 4. The composition of Claim 1, wherein R1 is selected from the group consisting of:
    In some embodiments, R1 is selected from the group consisting of:
    and derivatives thereof.
  5. Claim 5. The composition of Claim 1, wherein said compound is described by the following formula:

  6. Claim 6. The composition of Claim 1, wherein said compound is selected from the group consisting of:

  7. Claim 7. The composition of Claim 1, wherein said cells are selected from the group consisting of B cells, T cells, granulocytes, and proliferating cells.
  8. Claim 8. A method for regulating cell death, comprising a. providing:
    i. target cells;
    the composition described in Claim 1; and b. exposing said target cells to said composition under conditions such that said composition binds to said target cells so as to induce cellular apoptosis.
  9. Claim 9. The method of Claim 8, wherein said target cells are in vitro cells.
  10. Claim 10. The method of Claim 8, wherein said target cells are in vivo cells.
  11. Claim 11. The method of Claim 8, wherein said target cells are ex vivo cells.
  12. Claim 12. The method of Claim 8, wherein said target cells are cancer cells.
  13. Claim 13. The method of Claim 8, wherein said target cells are selected from the group consisting of B cells, T cells, and granulocytes.
  14. Claim 14. The method of Claim 8, wherein said target cells are proliferating cells.
  15. Claim 15. A method of treating autoimmune disorders, comprising:
    a) providing a subject and the composition described in Claim 1, wherein said composition is capable of inducing cellular apoptosis, and wherein said composition demonstrates selective cytotoxicity against T cells as compared to B cells; and b) administering said composition to said subject.
CA2628193A 2005-11-01 2006-11-01 Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties Expired - Fee Related CA2628193C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2779041A CA2779041A1 (en) 2005-11-01 2006-11-01 Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US73204505P 2005-11-01 2005-11-01
US60/732,045 2005-11-01
PCT/US2006/042753 WO2007053725A2 (en) 2005-11-01 2006-11-01 Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties

Related Child Applications (1)

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CA2779041A Division CA2779041A1 (en) 2005-11-01 2006-11-01 Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties

Publications (2)

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CA2628193A1 true CA2628193A1 (en) 2007-05-10
CA2628193C CA2628193C (en) 2012-08-14

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CA2779041A Abandoned CA2779041A1 (en) 2005-11-01 2006-11-01 Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties
CA2628193A Expired - Fee Related CA2628193C (en) 2005-11-01 2006-11-01 Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties

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US (3) US8088759B2 (en)
EP (2) EP1948191B1 (en)
JP (1) JP5241501B2 (en)
AU (2) AU2006308655B2 (en)
CA (2) CA2779041A1 (en)
IL (1) IL191175A (en)
NZ (1) NZ568254A (en)
WO (1) WO2007053725A2 (en)

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WO2007053193A2 (en) 2005-06-01 2007-05-10 The Regents Of The University Of Michigan Unsolvated benzodiazepine compositions and methods
WO2007053725A2 (en) 2005-11-01 2007-05-10 The Regents Of The University Of Michigan Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties
US7759338B2 (en) 2006-04-27 2010-07-20 The Regents Of The University Of Michigan Soluble 1,4 benzodiazepine compounds and stable salts thereof
EP2418206A3 (en) 2006-06-09 2012-06-27 The Regents of the University of Michigan Benzodiazepine derivatives useful in the treatment of autoimmune disorders
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CA2780333C (en) 2009-11-17 2016-05-24 The Regents Of The University Of Michigan 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
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