WO2000066106A3 - Use of benzodiazepines for treating autoimmune diseases induced by apoptosis - Google Patents

Use of benzodiazepines for treating autoimmune diseases induced by apoptosis Download PDF

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Publication number
WO2000066106A3
WO2000066106A3 PCT/US2000/011599 US0011599W WO0066106A3 WO 2000066106 A3 WO2000066106 A3 WO 2000066106A3 US 0011599 W US0011599 W US 0011599W WO 0066106 A3 WO0066106 A3 WO 0066106A3
Authority
WO
WIPO (PCT)
Prior art keywords
compounds
benzodiazepine
benzodiazepines
disorders
apoptosis
Prior art date
Application number
PCT/US2000/011599
Other languages
French (fr)
Other versions
WO2000066106A2 (en
WO2000066106A9 (en
Inventor
Gary D Glick
Anthony W Opipari Jr
Original Assignee
Univ Michigan
Gary D Glick
Anthony W Opipari Jr
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
Priority to EP00928586A priority Critical patent/EP1143946B1/en
Priority to DE60007960T priority patent/DE60007960T2/en
Application filed by Univ Michigan, Gary D Glick, Anthony W Opipari Jr filed Critical Univ Michigan
Priority to AU46802/00A priority patent/AU782447C/en
Priority to CA2372150A priority patent/CA2372150C/en
Priority to MXPA01011052A priority patent/MXPA01011052A/en
Priority to US09/700,101 priority patent/US7125866B1/en
Priority to AT00928586T priority patent/ATE258439T1/en
Priority to IL14622200A priority patent/IL146222A0/en
Priority to JP2000614991A priority patent/JP5127096B2/en
Publication of WO2000066106A2 publication Critical patent/WO2000066106A2/en
Priority to US09/767,283 priority patent/US7220739B2/en
Publication of WO2000066106A3 publication Critical patent/WO2000066106A3/en
Priority to IL146222A priority patent/IL146222A/en
Publication of WO2000066106A9 publication Critical patent/WO2000066106A9/en
Priority to US10/427,211 priority patent/US7572788B2/en
Priority to US10/795,535 priority patent/US7276348B2/en
Priority to US10/886,450 priority patent/US20060025388A1/en
Priority to US10/935,333 priority patent/US20050113460A1/en
Priority to AU2005227385A priority patent/AU2005227385C1/en
Priority to US11/585,492 priority patent/US20070036854A1/en
Priority to US11/643,614 priority patent/US8415343B2/en
Priority to US11/807,046 priority patent/US20090012065A1/en
Priority to US11/807,291 priority patent/US20070299059A1/en
Priority to US12/111,068 priority patent/US7683046B2/en
Priority to US12/728,716 priority patent/US8168626B2/en
Priority to US13/372,124 priority patent/US20120165301A1/en
Priority to US13/717,096 priority patent/US8722667B2/en
Priority to US13/896,876 priority patent/US8809323B2/en

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    • 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
    • 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
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
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    • 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
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C07D243/24—Oxygen atoms
    • 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
    • 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
    • C07D403/12—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 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
    • C07D413/02—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

Abstract

Benzodiazepine compounds, and methods for using those compounds are provided. Some of the benzodiazepine compounds include 1,4-benzodiazepine-2-one and 1.4-benzodiazepine-2,5-dione compounds of structures (I) or (II): wherein R1, R2, R3 and R4 are as defined. The invention also includes enantiomers, pharmaceutically acceptable salts, prodrugs or derivatives of the benzodiazepine compounds. Any one or more of these benzodiazepine compounds can be used to treat a variety of dysregulatory disorders related to cellular death. Such disorders include autoimmune disorders, inflammatory conditions, hyperproliferative conditions, viral infections, and atherosclerosis. In addition, the above compounds can be used to prepare medicaments to treat the above-described dysregulatory disorders. The benzodiazepines can also be used in drugs screening assays and other diagnostic methods.
PCT/US2000/011599 1995-05-18 2000-04-27 Use of benzodiazepines for treating autoimmune diseases induced by apoptosis WO2000066106A2 (en)

Priority Applications (25)

Application Number Priority Date Filing Date Title
JP2000614991A JP5127096B2 (en) 1999-04-30 2000-04-27 Use of benzodiazepines to treat autoimmune diseases induced by apoptosis
IL14622200A IL146222A0 (en) 1999-04-30 2000-04-27 Therapeutic applications of pro-apoptotic benzodiazepines
AU46802/00A AU782447C (en) 1999-04-30 2000-04-27 Use of benzodiazepines for treating autoimmune diseases induced by apoptosis
DE60007960T DE60007960T2 (en) 1999-04-30 2000-04-27 Therapeutic applications of pro-apoptotic benzodiazepines
MXPA01011052A MXPA01011052A (en) 1999-04-30 2000-04-27 Therapeutic applications of pro-apoptotic benzodiazepines.
US09/700,101 US7125866B1 (en) 1999-04-30 2000-04-27 Therapeutic applications of pro-apoptotic benzodiazepines
AT00928586T ATE258439T1 (en) 1999-04-30 2000-04-27 USE OF BENZODIAZEPINES TO TREAT APOPTOSIS-INDUCED AUTOIMMUNE DISEASES
EP00928586A EP1143946B1 (en) 1999-04-30 2000-04-27 Use of benzodiazepines for treating autoimmune diseases induced by apoptosis
CA2372150A CA2372150C (en) 1999-04-30 2000-04-27 Therapeutic applications of pro-apoptotic benzodiazepines
US09/767,283 US7220739B2 (en) 1995-05-18 2001-01-22 Therapeutic application of pro-apoptotic benzodiazepines
IL146222A IL146222A (en) 1999-04-30 2001-10-29 Use of compositions comprising benzodiazepines for the manufacture of medicaments for the treatment of conditions associated with dysregulation of cell death and pharmaceutical compositions thereof
US10/427,211 US7572788B2 (en) 1999-04-30 2003-05-01 Compositions and methods relating to novel compounds and targets thereof
US10/795,535 US7276348B2 (en) 1999-04-30 2004-03-08 Compositions and methods relating to F1F0-ATPase inhibitors and targets thereof
US10/886,450 US20060025388A1 (en) 1999-04-30 2004-07-07 Compositions and methods relating to novel compounds and targets thereof
US10/935,333 US20050113460A1 (en) 1999-04-30 2004-09-07 Compositions and methods relating to novel compounds and targets thereof
AU2005227385A AU2005227385C1 (en) 1999-04-30 2005-10-27 Use of benzodiazepines for treating autoimmune diseases induced by apoptosis
US11/585,492 US20070036854A1 (en) 1999-04-30 2006-10-23 Therapeutic applications of pro-apoptotic benzodiazepines
US11/643,614 US8415343B2 (en) 1999-04-30 2006-12-21 Compositions and methods for inhibiting the proliferation of cells
US11/807,046 US20090012065A1 (en) 1999-04-30 2007-05-25 Therapeutic applications of pro-apoptotic benzodiazepines
US11/807,291 US20070299059A1 (en) 1999-04-30 2007-05-25 Compostions and methods relating to novel compounds and targets thereof
US12/111,068 US7683046B2 (en) 1999-04-30 2008-04-28 Benzodiazepine compositions for treating epidermal hyperplasia and related disorders
US12/728,716 US8168626B2 (en) 1999-04-30 2010-03-22 Benzodiazepine compositions for treating epidermal hyperplasia and related disorders
US13/372,124 US20120165301A1 (en) 1999-04-30 2012-02-13 Benzodiazepine compositions for treating epidermal hyperplasia and related disorders
US13/717,096 US8722667B2 (en) 1999-04-30 2012-12-17 Compositions and methods for inhibiting the proliferation of cells
US13/896,876 US8809323B2 (en) 1999-04-30 2013-05-17 Therapeutic applications of pro-apoptotic benzodiazepines

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US13176199P 1999-04-30 1999-04-30
US60/131,761 1999-04-30
US16551199P 1999-11-15 1999-11-15
US60/165,511 1999-11-15
US19185500P 2000-03-24 2000-03-24
US60/191,855 2000-03-24

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
US08/881,037 Continuation-In-Part US6080588A (en) 1995-05-18 1997-06-23 Therapeutic methods for benzodiazepine derivatives
US1802698A Continuation-In-Part 1995-05-18 1998-02-02

Related Child Applications (3)

Application Number Title Priority Date Filing Date
US09/700,101 A-371-Of-International US7125866B1 (en) 1995-05-18 2000-04-27 Therapeutic applications of pro-apoptotic benzodiazepines
US09/767,283 Continuation US7220739B2 (en) 1995-05-18 2001-01-22 Therapeutic application of pro-apoptotic benzodiazepines
US11/585,492 Continuation US20070036854A1 (en) 1999-04-30 2006-10-23 Therapeutic applications of pro-apoptotic benzodiazepines

Publications (3)

Publication Number Publication Date
WO2000066106A2 WO2000066106A2 (en) 2000-11-09
WO2000066106A3 true WO2000066106A3 (en) 2001-08-16
WO2000066106A9 WO2000066106A9 (en) 2002-04-18

Family

ID=27384197

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/011599 WO2000066106A2 (en) 1995-05-18 2000-04-27 Use of benzodiazepines for treating autoimmune diseases induced by apoptosis

Country Status (13)

Country Link
US (5) US7125866B1 (en)
EP (4) EP1398033B1 (en)
JP (1) JP5127096B2 (en)
AT (2) ATE258439T1 (en)
AU (2) AU782447C (en)
CA (1) CA2372150C (en)
DE (2) DE60007960T2 (en)
DK (1) DK1143946T3 (en)
ES (1) ES2214273T3 (en)
IL (2) IL146222A0 (en)
MX (1) MXPA01011052A (en)
PT (1) PT1143946E (en)
WO (1) WO2000066106A2 (en)

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EP2062583A3 (en) 2009-12-30
ES2214273T3 (en) 2004-09-16
ATE258439T1 (en) 2004-02-15
CA2372150A1 (en) 2000-11-09
US7220739B2 (en) 2007-05-22
ATE433752T1 (en) 2009-07-15
DE60042425D1 (en) 2009-07-30
EP2062583A2 (en) 2009-05-27
JP5127096B2 (en) 2013-01-23
DE60007960D1 (en) 2004-03-04
AU2005227385B2 (en) 2008-12-11
IL146222A0 (en) 2002-07-25
DE60007960T2 (en) 2004-10-21
JP2002543121A (en) 2002-12-17
AU4680200A (en) 2000-11-17
AU2005227385A1 (en) 2005-12-01
AU782447B2 (en) 2005-07-28
CA2372150C (en) 2011-08-30
EP1398033A3 (en) 2004-06-30
PT1143946E (en) 2004-05-31

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