WO2003012030A3 - Isoform-selective inhibitors and activators of pde3 cyclic - Google Patents

Isoform-selective inhibitors and activators of pde3 cyclic Download PDF

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Publication number
WO2003012030A3
WO2003012030A3 PCT/US2002/019319 US0219319W WO03012030A3 WO 2003012030 A3 WO2003012030 A3 WO 2003012030A3 US 0219319 W US0219319 W US 0219319W WO 03012030 A3 WO03012030 A3 WO 03012030A3
Authority
WO
WIPO (PCT)
Prior art keywords
pde3
activators
methods
selective inhibitors
isoform
Prior art date
Application number
PCT/US2002/019319
Other languages
French (fr)
Other versions
WO2003012030A2 (en
Inventor
Matthew Movsesian
Original Assignee
Univ Utah Technology Transfer
Matthew Movsesian
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 Univ Utah Technology Transfer, Matthew Movsesian filed Critical Univ Utah Technology Transfer
Priority to DE60237696T priority Critical patent/DE60237696D1/en
Priority to AT02739923T priority patent/ATE481497T1/en
Priority to EP02739923A priority patent/EP1430140B1/en
Priority to AU2002312543A priority patent/AU2002312543A1/en
Priority to JP2003517208A priority patent/JP2004536614A/en
Publication of WO2003012030A2 publication Critical patent/WO2003012030A2/en
Publication of WO2003012030A3 publication Critical patent/WO2003012030A3/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/18—Carboxylic ester hydrolases (3.1.1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/916—Hydrolases (3) acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)

Abstract

The present invention concerns methods and compositions related to type 3 phosphodiesterases (PDE3). Certain embodiments concern isolated peptides corresponding to various PDE3A isiforms and/or site-specific mutants of PDE3A isoforms, along with expression vectors encoding such isoforms or mutants. In specific embodiments, methods for identifying isoform selective inhibitors or activators of PDE3 are provided, along with methods of use of such inhibitors or activators in the treatment of dilated cardiomyopathy, pulmonary hypertension and/or other medical conditions related to PDE3 effects on cAMP levels in different intracellular compartments.
PCT/US2002/019319 2001-08-01 2002-06-19 Isoform-selective inhibitors and activators of pde3 cyclic WO2003012030A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
DE60237696T DE60237696D1 (en) 2001-08-01 2002-06-19 AT N-TERMINUS TRUNCATED ISOFORMS OF CYCLIC PHOSPHODIESTERASES PDE3A
AT02739923T ATE481497T1 (en) 2001-08-01 2002-06-19 N-TERMINUS TRUNCATED ISOFORMS OF CYCLIC PHOSPHODIESTERASES PDE3A
EP02739923A EP1430140B1 (en) 2001-08-01 2002-06-19 N-terminally truncated isoforms of pde3a cyclic phosphodiesterases
AU2002312543A AU2002312543A1 (en) 2001-08-01 2002-06-19 Isoform-selective inhibitors and activators of pde3 cyclic
JP2003517208A JP2004536614A (en) 2001-08-01 2002-06-19 PDE3 cyclic nucleotide phosphodiesterase isoform-selective inhibitors and activators

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US30927101P 2001-08-01 2001-08-01
US60/309,271 2001-08-01

Publications (2)

Publication Number Publication Date
WO2003012030A2 WO2003012030A2 (en) 2003-02-13
WO2003012030A3 true WO2003012030A3 (en) 2004-04-08

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/019319 WO2003012030A2 (en) 2001-08-01 2002-06-19 Isoform-selective inhibitors and activators of pde3 cyclic

Country Status (7)

Country Link
US (3) US20030158133A1 (en)
EP (1) EP1430140B1 (en)
JP (1) JP2004536614A (en)
AT (1) ATE481497T1 (en)
AU (1) AU2002312543A1 (en)
DE (1) DE60237696D1 (en)
WO (1) WO2003012030A2 (en)

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PROC. NATL. ACAD. SCI. USA, vol. 89, 1992, pages 3721 - 3725 *

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