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WO1994000095A3 - Use of calpain inhibitors in the inhibition and treatment of medical conditions associated with increased calpain activity - Google Patents

Use of calpain inhibitors in the inhibition and treatment of medical conditions associated with increased calpain activity Download PDF

Info

Publication number
WO1994000095A3
WO1994000095A3 PCT/US1993/006143 US9306143W WO9400095A3 WO 1994000095 A3 WO1994000095 A3 WO 1994000095A3 US 9306143 W US9306143 W US 9306143W WO 9400095 A3 WO9400095 A3 WO 9400095A3
Authority
WO
WIPO (PCT)
Prior art keywords
smooth muscle
calpain
compounds
present
methods
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1993/006143
Other languages
French (fr)
Other versions
WO1994000095A2 (en
Inventor
David D Eveleth Jr
Gary Lynch
James C Powers
Raymond T Bartus
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Georgia Tech Research Institute
Georgia Tech Research Corp
Cortex Pharmaceuticals Inc
Original Assignee
Georgia Tech Research Institute
Georgia Tech Research Corp
Cortex Pharmaceuticals Inc
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 Georgia Tech Research Institute, Georgia Tech Research Corp, Cortex Pharmaceuticals Inc filed Critical Georgia Tech Research Institute
Priority to JP6502621A priority Critical patent/JPH09500087A/en
Priority to AU45449/93A priority patent/AU4544993A/en
Priority to EP93915482A priority patent/EP0650368A1/en
Publication of WO1994000095A2 publication Critical patent/WO1994000095A2/en
Publication of WO1994000095A3 publication Critical patent/WO1994000095A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/12—Ophthalmic agents for cataracts
    • 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
    • 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
    • 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
    • A61P9/12—Antihypertensives

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Cardiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides a method of treating a medical condition associated with increased proteolytic activity of Calpain in a mammal. The method includes administering a pharmaceutical composition containing a Calpain inhibitor compound to the mammal in an amount that is pharmacologically effective to treat the condition. The inhibitor is a compound in one of the following groups of compounds: Peptide Keto-Compounds, Substituted Heterocyclic Compounds or Halo-Ketone Peptides. Examples of conditions that can be treated using the methods of the present invention include cardiac muscle tissue damage, cataracts, smooth muscle damage and vasospasm. The present invention also provides a method of inhibiting smooth muscle cell proliferation and thereby preventing the restenosis of a blood vessel which has been undergone therapeutic angioplasty. This method includes the administration of a calpain inhibitor to the blood vessel during or after the angioplasty procedure. Further, methods of blocking the establishment of the tonically contracted state in smooth muscle and relaxing tonically contracted smooth muscle are disclosed. These methods involve the administration of a calpain inhibitor, thereby reducing or preventing smooth muscle contraction associated with vasospasm and bronchospasm.
PCT/US1993/006143 1992-06-24 1993-06-24 Use of calpain inhibitors in the inhibition and treatment of medical conditions associated with increased calpain activity Ceased WO1994000095A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP6502621A JPH09500087A (en) 1992-06-24 1993-06-24 Use of calpain inhibitors in the control and treatment of health disorders associated with increased calpain activity.
AU45449/93A AU4544993A (en) 1992-06-24 1993-06-24 Use of calpain inhibitors in the inhibition and treatment of medical conditions associated with increased calpain activity
EP93915482A EP0650368A1 (en) 1992-06-24 1993-06-24 Use of calpain inhibitors in the inhibition and treatment of medical conditions associated with increased calpain activity

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US90380092A 1992-06-24 1992-06-24
US3499693A 1993-03-16 1993-03-16
US7260993A 1993-06-01 1993-06-01
US07/903,800 1993-06-01
US08/034,996 1993-06-01
US08/072,609 1993-06-01

Publications (2)

Publication Number Publication Date
WO1994000095A2 WO1994000095A2 (en) 1994-01-06
WO1994000095A3 true WO1994000095A3 (en) 1994-03-17

Family

ID=27364781

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1993/006143 Ceased WO1994000095A2 (en) 1992-06-24 1993-06-24 Use of calpain inhibitors in the inhibition and treatment of medical conditions associated with increased calpain activity

Country Status (5)

Country Link
EP (1) EP0650368A1 (en)
JP (1) JPH09500087A (en)
AU (1) AU4544993A (en)
CA (1) CA2138124A1 (en)
WO (1) WO1994000095A2 (en)

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US5541290A (en) * 1993-06-24 1996-07-30 Harbeson; Scott L. Optically pure calpain inhibitor compounds
US6660268B1 (en) * 1994-03-18 2003-12-09 The President And Fellows Of Harvard College Proteasome regulation of NF-KB activity
EP0793673A1 (en) * 1994-11-24 1997-09-10 Takeda Chemical Industries, Ltd. Alpha-ketoamide derivatives as cathepsin l inhibitor
US5863902A (en) * 1995-01-06 1999-01-26 Sibia Neurosciences, Inc. Methods of treating neurodegenerative disorders using protease inhibitors
US5804560A (en) * 1995-01-06 1998-09-08 Sibia Neurosciences, Inc. Peptide and peptide analog protease inhibitors
US5723580A (en) * 1995-09-14 1998-03-03 Cephalon, Inc. Ketomethylene group-containing aldehyde cysteine and serine protease inhibitors
US5827877A (en) * 1995-09-14 1998-10-27 Cephalon, Inc. Ketomethylene group-containing cysteine and serine protease inhibitors
US6586466B2 (en) 1995-10-30 2003-07-01 Smithkline Beecham Corporation Carbohydrazide-protease inhibitors
SK56798A3 (en) * 1995-10-30 1998-12-02 Smithkline Beecham Corp Protease inhibitors, pharmaceutical composition containing them and their use
ES2293651T3 (en) * 1995-11-28 2008-03-16 Cephalon, Inc. INHIBITORS OF CYSTEINE AND SERINE PROTEASES DERIVED FROM AMINO ACIDS D.
US5834503A (en) * 1996-06-14 1998-11-10 Qlt Phototherapeutics, Inc. Methods to treat arterial plaque
DE19642591A1 (en) 1996-10-15 1998-04-16 Basf Ag New piperidine-ketocarboxylic acid derivatives, their production and use
US6303579B1 (en) 1996-10-31 2001-10-16 Alcon Laboratories, Inc. Use of calpain inhibitors to treat ocular neural pathology
DE19650975A1 (en) 1996-12-09 1998-06-10 Basf Ag New heterocyclically substituted benzamides and their application
PL334059A1 (en) * 1996-12-11 2000-01-31 Basf Ag Ketone benzamides useful as calpain inhibitors
JP2002161051A (en) * 1996-12-24 2002-06-04 Fujisawa Pharmaceut Co Ltd Therapeutic agent for cerebral ischemic disease or the like
DE19817459A1 (en) 1998-04-20 1999-10-21 Basf Ag New heterocyclic amide derivatives useful as cysteine protease inhibitors for treating neurodegenerative diseases, neuronal damage, stroke, cranial trauma, Alzheimer's disease, etc.
JP4621351B2 (en) 1998-04-20 2011-01-26 アボット ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト Heterocyclically substituted amides as calpain inhibitors
WO1999054310A2 (en) 1998-04-20 1999-10-28 Basf Aktiengesellschaft New substituted amides, their production and their use
DE19818614A1 (en) 1998-04-20 1999-10-21 Basf Ag New benzamide derivatives useful as cysteine protease inhibitors for treating neurodegenerative diseases, neuronal damage, stroke, cranial trauma, Alzheimer's disease, etc.
US6841537B1 (en) 1998-04-22 2005-01-11 Protiva Biotherapeutics Inc. Combination therapy using nucleic acids and conventional drugs
CA2325561A1 (en) * 1998-04-22 1999-10-28 Inex Pharmaceuticals Corporation Combination therapy using nucleic acids and conventional drugs
US6841538B1 (en) * 1998-04-22 2005-01-11 Inex Pharmaceuticals Corporation Combination therapy using nucleic acids and radio therapy
IL139357A0 (en) 1998-05-25 2001-11-25 Basf Ag New heterocyclically substituted amides, their production and their use
DE19847422C1 (en) * 1998-10-14 2000-01-13 Forschungszentrum Juelich Gmbh Chinese hamster ovary cells, useful for large-scale production of recombinant proteins, especially enzymes
US20030144175A1 (en) 1998-12-23 2003-07-31 Smithkline Beecham Corporation Protease inhibitors
US6596715B1 (en) 1999-11-10 2003-07-22 Smithkline Beecham Corporation Protease inhibitors
EP1232154A4 (en) 1999-11-10 2004-06-23 Smithkline Beecham Corp Protease inhibitors
AU1474801A (en) 1999-11-10 2001-06-06 Smithkline Beecham Corporation Protease inhibitors
EA005893B1 (en) 2000-03-21 2005-06-30 Смитклайн Бичам Корпорейшн Protease inhibitors
US7244721B2 (en) 2000-07-21 2007-07-17 Schering Corporation Peptides as NS3-serine protease inhibitors of hepatitis C virus
IL153670A0 (en) 2000-07-21 2003-07-06 Schering Corp Novel peptides as ns3-serine protease inhibitors of hepatitis c virus
CZ2003195A3 (en) 2000-07-21 2003-04-16 Schering Corporation Peptide inhibitors of serine protease NS3 and pharmaceutical preparation containing thereof
GB0106051D0 (en) * 2001-03-12 2001-05-02 Isis Innovation Diagnostic screens for alzheimer's disease
GB0117645D0 (en) * 2001-07-19 2001-09-12 Isis Innovation Therapeutic stratergies for prevention and treatment of alzheimers disease
US6610874B2 (en) 2001-09-28 2003-08-26 Pcbu Services, Inc. Processes and compositions for the production of chiral amino-nitriles
WO2003062192A1 (en) 2002-01-17 2003-07-31 Smithkline Beecham Corporation Cycloalkyl ketoamides derivatives useful as cathepsin k inhibitors
US7491705B2 (en) 2003-12-12 2009-02-17 Senju Pharmaceutical Co., Ltd. Alpha-ketoamide derivative, and production method and use thereof
KR101447897B1 (en) * 2005-03-21 2014-10-07 비로베이, 인코포레이티드 Alpha ketoamide compounds as cysteine protease inhibitors
GB2467562A (en) * 2009-02-06 2010-08-11 Summit Corp Plc Dual calpain-ROS inhibitors
WO2013067415A1 (en) * 2011-11-02 2013-05-10 Tufts University Identification and use of protease inhibitors to treat or prevent sickle cell disease
CN102988336A (en) * 2012-05-17 2013-03-27 中国人民解放军第二军医大学 Use of TPCK (N-tosyl-L-phenylanyl chloromethyl ketone) in preparation of anti-lenticular opacity products
US10294269B2 (en) * 2014-09-08 2019-05-21 Landsteiner Genmed, S.L. Dipeptidyl ketoamide compounds and their use for the treatment and/or prevention of fat accumulation
JP6501353B2 (en) * 2015-05-07 2019-04-17 国立大学法人山口大学 Inhibitors of SPC / Fyn / Rho kinase signaling pathway
US10590084B2 (en) 2016-03-09 2020-03-17 Blade Therapeutics, Inc. Cyclic keto-amide compounds as calpain modulators and methods of production and use thereof
WO2018009417A1 (en) 2016-07-05 2018-01-11 Blade Therapeutics, Inc. Calpain modulators and therapeutic uses thereof
CA3038331A1 (en) 2016-09-28 2018-04-05 Blade Therapeutics, Inc. Calpain modulators and therapeutic uses thereof
MX2020010033A (en) * 2018-03-28 2020-10-14 Blade Therapeutics Inc Calpain modulators and therapeutic uses thereof.
EP3774785A4 (en) * 2018-03-28 2021-12-01 Blade Therapeutics, Inc. METHODS FOR TREATMENT OF FIBROTIC DISEASES
US20210179543A1 (en) * 2018-08-13 2021-06-17 Western University Of Health Sciences Calpain-2 selective inhibitor compounds for treatment of glaucoma
EP4488264A1 (en) * 2022-03-01 2025-01-08 WestVac Biopharma Co., Ltd. Keto amide derivatives and pharmaceutical use thereof

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US4771123A (en) * 1986-03-11 1988-09-13 Enzyme Systems Products, Inc. Peptide thioneamides as selective substrates for cysteine proteases
US4845242A (en) * 1987-04-28 1989-07-04 Georgia Tech Research Corporation Isocoumarins with basic substituents as serine proteases inhibitors, anticoagulants and anti-inflammatory agents
US5081284A (en) * 1989-04-10 1992-01-14 Suntory Limited Proteinase inhibitor
US5189144A (en) * 1989-04-28 1993-02-23 Takara Shuzo Co., Ltd. Human calpastatin-like polypeptide

Patent Citations (5)

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US4771123A (en) * 1986-03-11 1988-09-13 Enzyme Systems Products, Inc. Peptide thioneamides as selective substrates for cysteine proteases
EP0275101A2 (en) * 1987-01-16 1988-07-20 Merrell Dow Pharmaceuticals Inc. Novel peptidase inhibitors
US4845242A (en) * 1987-04-28 1989-07-04 Georgia Tech Research Corporation Isocoumarins with basic substituents as serine proteases inhibitors, anticoagulants and anti-inflammatory agents
US5081284A (en) * 1989-04-10 1992-01-14 Suntory Limited Proteinase inhibitor
US5189144A (en) * 1989-04-28 1993-02-23 Takara Shuzo Co., Ltd. Human calpastatin-like polypeptide

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BIOCHEMISTRY, Volume 24, issued 1985, J.W. HARPER et al., "Reaction of Serine Proteases with Substituted Isocoumarins: Discovery of 3,4 Dichlorosocoumarin. a new general Mechanism Based Serine Protease Inhibitor", pages 1831-1841. *
D. RICH, "Proteinase Inhibitors", Published 1986 by ELSEVIER SCIENCE PUBLISHERS BV., pages 153-178. *

Also Published As

Publication number Publication date
AU4544993A (en) 1994-01-24
CA2138124A1 (en) 1994-01-06
EP0650368A1 (en) 1995-05-03
WO1994000095A2 (en) 1994-01-06
JPH09500087A (en) 1997-01-07

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