CA2223595A1 - Prevention and treatment of cardiovascular pathologies with tamoxifen analogues - Google Patents

Prevention and treatment of cardiovascular pathologies with tamoxifen analogues

Info

Publication number
CA2223595A1
CA2223595A1 CA002223595A CA2223595A CA2223595A1 CA 2223595 A1 CA2223595 A1 CA 2223595A1 CA 002223595 A CA002223595 A CA 002223595A CA 2223595 A CA2223595 A CA 2223595A CA 2223595 A1 CA2223595 A1 CA 2223595A1
Authority
CA
Canada
Prior art keywords
alkyl
beta
tgf
ethyl
formula
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.)
Granted
Application number
CA002223595A
Other languages
French (fr)
Other versions
CA2223595C (en
Inventor
David J. Grainger
James C. Metcalfe
Lawrence L.. Kunz
Paul R. Kemp
Robert W. Schroff
Peter L. Weissberg
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.)
Poniard Pharmaceuticals Inc
Original Assignee
Neorx Corporation
David J. Grainger
James C. Metcalfe
Lawrence L.. Kunz
Paul R. Kemp
Robert W. Schroff
Peter L. Weissberg
Poniard 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
Priority claimed from US08/476,735 external-priority patent/US5595722A/en
Priority claimed from US08/486,334 external-priority patent/US5770609A/en
Priority claimed from US08/477,393 external-priority patent/US6395494B1/en
Application filed by Neorx Corporation, David J. Grainger, James C. Metcalfe, Lawrence L.. Kunz, Paul R. Kemp, Robert W. Schroff, Peter L. Weissberg, Poniard Pharmaceuticals, Inc. filed Critical Neorx Corporation
Publication of CA2223595A1 publication Critical patent/CA2223595A1/en
Application granted granted Critical
Publication of CA2223595C publication Critical patent/CA2223595C/en
Anticipated expiration legal-status Critical
Expired - Fee Related 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/32—Cardiovascular disorders
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/32—Cardiovascular disorders
    • G01N2800/324—Coronary artery diseases, e.g. angina pectoris, myocardial infarction

Abstract

A method for treating or preventing cardiovascular pathologies by administering a compound of formula (I), wherein Z is C=O or a covalent bond; Y is H or O(C1-C4)alkyl, R1 and R2 are individually (C1-C4)alkyl or together with N are a saturated heterocyclic group, R3 is ethyl or chloroethyl, R4 is H, R5 is I, O(C1-C4)alkyl or H and R6 is I, O(C1-C4)alkyl or H with the proviso that when R4, R5, and R6 are H, R3 is not ethyl; or a pharmaceutically acceptable salt thereof, effective to elevate the level of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke is provided. Useful compounds include idoxifene, toremifene or salts thereof. Further provided is a method for identifying an agent that elevates the level of TGF-beta. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro. Also provided is a therapeutic method comprising inhibiting smooth muscle cell proliferation associated with procedural vascular trauma employing the administration of tamoxifen or structural analogs thereof, including compounds of formula (I).
CA002223595A 1995-06-07 1996-06-07 Prevention and treatment of cardiovascular pathologies with tamoxifen analogues Expired - Fee Related CA2223595C (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US47893695A 1995-06-07 1995-06-07
US08/476,735 US5595722A (en) 1993-01-28 1995-06-07 Method for identifying an agent which increases TGF-beta levels
US08/486,334 US5770609A (en) 1993-01-28 1995-06-07 Prevention and treatment of cardiovascular pathologies
US08/486,334 1995-06-07
US08/477,393 US6395494B1 (en) 1993-05-13 1995-06-07 Method to determine TGF-β
US08/476,735 1995-06-07
US08/478,936 1995-06-07
US08/477,393 1995-06-07
PCT/US1996/010211 WO1996040098A2 (en) 1995-06-07 1996-06-07 Prevention and treatment of cardiovascular pathologies with tamoxifen analogues

Publications (2)

Publication Number Publication Date
CA2223595A1 true CA2223595A1 (en) 1996-12-19
CA2223595C CA2223595C (en) 2008-08-05

Family

ID=27504217

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002223595A Expired - Fee Related CA2223595C (en) 1995-06-07 1996-06-07 Prevention and treatment of cardiovascular pathologies with tamoxifen analogues

Country Status (7)

Country Link
US (3) US6197789B1 (en)
EP (1) EP0833624B1 (en)
JP (1) JPH11510479A (en)
AT (1) ATE377418T1 (en)
AU (1) AU6277396A (en)
CA (1) CA2223595C (en)
WO (1) WO1996040098A2 (en)

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