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
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
Original Assignee
Cortex Pharma Inc
Georgia Tech Res Inst
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 Cortex Pharma Inc, Georgia Tech Res Inst filed Critical Cortex Pharma Inc
Priority to EP93915482A priority Critical patent/EP0650368A1/en
Priority to JP6502621A priority patent/JPH09500087A/en
Priority to AU45449/93A priority patent/AU4544993A/en
Publication of WO1994000095A2 publication Critical patent/WO1994000095A2/en
Publication of WO1994000095A3 publication Critical patent/WO1994000095A3/en

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 WO1994000095A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
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
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

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 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)

Families Citing this family (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
AU3935895A (en) * 1994-11-24 1996-06-17 Takeda Chemical Industries Ltd. Alpha-ketoamide derivatives as cathepsin l inhibitor
US6017887A (en) * 1995-01-06 2000-01-25 Sibia Neurosciences, Inc. Peptide, peptide analog and amino acid analog protease inhibitors
US5804560A (en) * 1995-01-06 1998-09-08 Sibia Neurosciences, Inc. Peptide and peptide analog protease inhibitors
US5827877A (en) * 1995-09-14 1998-10-27 Cephalon, Inc. Ketomethylene group-containing cysteine and serine protease inhibitors
US5723580A (en) * 1995-09-14 1998-03-03 Cephalon, Inc. Ketomethylene group-containing aldehyde cysteine and serine protease inhibitors
US6586466B2 (en) 1995-10-30 2003-07-01 Smithkline Beecham Corporation Carbohydrazide-protease inhibitors
KR19990067184A (en) 1995-10-30 1999-08-16 스튜어트 알. 수터, 스티븐 베네티아너, 피터 존 기딩스 Protease inhibitor
DE69637307T2 (en) * 1995-11-28 2008-02-28 Cephalon, Inc. CYSTEIN AND SERINE PROTEASE INHIBITORS DERIVED FROM D-AMINO ACIDS
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
AU721620B2 (en) * 1996-12-11 2000-07-13 Basf Aktiengesellschaft Novel ketobenzamides and their use
JP2002161051A (en) * 1996-12-24 2002-06-04 Fujisawa Pharmaceut Co Ltd Therapeutic agent for cerebral ischemic disease or the like
SK14512000A3 (en) 1998-04-20 2001-04-09 Basf Aktiengesellschaft New substituted amides, their production and their use
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.
WO1999054305A1 (en) 1998-04-20 1999-10-28 Basf Aktiengesellschaft Heterocyclically substituted amides used as calpain inhibitors
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
US6841538B1 (en) * 1998-04-22 2005-01-11 Inex Pharmaceuticals Corporation Combination therapy using nucleic acids and radio therapy
AU762986B2 (en) * 1998-04-22 2003-07-10 Inex Pharmaceuticals Corporation Combination therapy using nucleic acids and conventional drugs
EP1080074B1 (en) 1998-05-25 2006-11-08 Abbott GmbH & Co. KG Heterocyclic 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
WO2001034600A1 (en) 1999-11-10 2001-05-17 Smithkline Beecham Corporation Protease inhibitors
WO2001034599A1 (en) 1999-11-10 2001-05-17 Smithkline Beecham Corporation Protease inhibitors
US6534498B1 (en) 1999-11-10 2003-03-18 Smithkline Beecham Corporation Protease inhibitors
AU2001243441B2 (en) 2000-03-21 2004-11-25 Smithkline Beecham Corporation Protease inhibitors
MXPA03000626A (en) 2000-07-21 2004-07-30 Schering Corp Novel peptides as ns3-serine protease inhibitors of hepatitis c virus.
CN102372764A (en) 2000-07-21 2012-03-14 先灵公司 Novel peptides as NS3-serine protease inhibitors of hepatitis c virus
US7244721B2 (en) 2000-07-21 2007-07-17 Schering Corporation Peptides as NS3-serine protease inhibitors of hepatitis C virus
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
JP2005515254A (en) 2002-01-17 2005-05-26 スミスクライン ビーチャム コーポレーション Cycloalkylketoamide derivatives useful as cathepsin K inhibitors
DE602004023873D1 (en) 2003-12-12 2009-12-10 Senju Pharma Co USE OF THIS
EA017874B1 (en) * 2005-03-21 2013-03-29 Вайробей, Инк. 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
JP6533580B2 (en) * 2014-09-08 2019-06-19 ランドステイナー ジェンメド、エセ．エレ．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
US10934261B2 (en) 2016-09-28 2021-03-02 Blade Therapeutics, Inc. Calpain modulators and therapeutic uses thereof
SG11202008773PA (en) * 2018-03-28 2020-10-29 Blade Therapeutics Inc Method of treating fibrotic disease
AU2019242387A1 (en) * 2018-03-28 2020-11-19 Blade Therapeutics, Inc. Calpain modulators and therapeutic uses thereof
WO2023165334A1 (en) * 2022-03-01 2023-09-07 成都威斯克生物医药有限公司 Keto amide derivatives and pharmaceutical use thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0275101A2 (en) * 1987-01-16 1988-07-20 Merrell Dow Pharmaceuticals Inc. Novel peptidase inhibitors
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
EP0650368A1 (en) 1995-05-03
WO1994000095A2 (en) 1994-01-06
CA2138124A1 (en) 1994-01-06
AU4544993A (en) 1994-01-24
JPH09500087A (en) 1997-01-07

Similar Documents

Publication Publication Date Title
WO1994000095A3 (en) Use of calpain inhibitors in the inhibition and treatment of medical conditions associated with increased calpain activity
Lund et al. Glyceryl trinitrate is an effective treatment for anal fissure
ATE287271T1 (en) USE OF VEGF FOR PRODUCING A MEDICATION FOR TREATING OR PREVENTING INTIMAL HYPERPLASIA AND ADMINISTRATION DEVICE
RU2008150750A (en) MEDICINES ADMINISTRATION SYSTEMS CONTAINING RAPAMICIN AND ITS DERIVATIVES THAT ARE INTENDED FOR THE PREVENTION AND TREATMENT OF VASCULAR DISEASES
ATE245434T1 (en) USE OF A DIPEPTIDE FOR RESTORATION PROCESSES
WO1998033491A3 (en) Treatment of arrhythmias via inhibition of a multifunctional calcium/calmodulin-dependent protein kinase
EP1297840A3 (en) Methods for treating sex hormone-dependent conditions with LHRH antagonists
EA200401043A1 (en) Treatment of benign prostatic hyperplasia by the selective modulator of the androgen receptor (sarm)
GB9106678D0 (en) Wound healing
WO2009129437A3 (en) Methods and compositions for treating post-operative pain comprising clonidine
NO20014046L (en) Gabapentin derivatives for the prevention and treatment of visceral pain
DE3853459T2 (en) Treatment of glaucoma.
UA35567C2 (en) Pharmaceutical preparation for treating patients with coagulation impairment, method for treatment, method for pharmaceutical manufacturing
FR2712811B1 (en) Method for combating adipositis and compositions which can be used for this purpose.
CA2156481A1 (en) 5-ht2 receptor antagonist compositions useful in treating venous conditions
DE69808131T2 (en) METHOD FOR PREVENTING AND TREATING MYOCARDIAL STUNNING
MY118986A (en) Use of (alpha)-1-adrenoreceptor antagonists in the prevention and treatment of benign prostatic hyperplasia
SE9703929D0 (en) Therapeutic use and method
Francesco et al. Effects of gabexate mesilate, a protease inhibitor, on human sphincter of Oddi motility
CA2136953A1 (en) A method for using lipoprotein associated coagulation inhibitor to treat sepsis
CA2289017A1 (en) The use of a nitroxide or a prodrug thereof in the prophylactic and therapeutic treatment of cancer
NO965247L (en) Use of cross-linked hemoglobin in the treatment of subarakuoid hemorrhage
WO1997026880A3 (en) Use of a combination of delavirdine and one or more protease inhibitors in hiv-1 infected patients
WO2003044040A3 (en) Alpha-fetoprotein peptides and uses thereof
NO20016301L (en) Therapeutic agents

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AT AU BB BG BR CA CH CZ DE DK ES FI GB HU JP KP KR KZ LK LU MG MN MW NL NO NZ PL PT RO RU SD SE SK UA US VN

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

AK Designated states

Kind code of ref document: A3

Designated state(s): AT AU BB BG BR CA CH CZ DE DK ES FI GB HU JP KP KR KZ LK LU MG MN MW NL NO NZ PL PT RO RU SD SE SK UA US VN

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 253962

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 2138124

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 1993915482

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 1993915482

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 1995 362578

Country of ref document: US

Date of ref document: 19950505

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 1995 459753

Country of ref document: US

Date of ref document: 19950602

Kind code of ref document: A

WWW Wipo information: withdrawn in national office

Ref document number: 1993915482

Country of ref document: EP