WO2008130632A3 - Procédés d'augmentation des niveaux de camp et leurs utilisations - Google Patents

Procédés d'augmentation des niveaux de camp et leurs utilisations Download PDF

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Publication number
WO2008130632A3
WO2008130632A3 PCT/US2008/005026 US2008005026W WO2008130632A3 WO 2008130632 A3 WO2008130632 A3 WO 2008130632A3 US 2008005026 W US2008005026 W US 2008005026W WO 2008130632 A3 WO2008130632 A3 WO 2008130632A3
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WO
WIPO (PCT)
Prior art keywords
present
methods
cilostazol
akt
camp levels
Prior art date
Application number
PCT/US2008/005026
Other languages
English (en)
Other versions
WO2008130632A2 (fr
Inventor
Yochai Birnbaum
Original Assignee
Univ Texas
Yochai Birnbaum
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 Texas, Yochai Birnbaum filed Critical Univ Texas
Publication of WO2008130632A2 publication Critical patent/WO2008130632A2/fr
Publication of WO2008130632A3 publication Critical patent/WO2008130632A3/fr

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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
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne les effets bénéfiques supplémentaires du cilastazol, un inhibiteur de la phosphodiestérase 3, par rapport à l'atorvastatine sur le remodelage myocardique par l'induction et la préservation de la phosphorylation de eNOS. La présente invention concerne un effet cardioprotecteur du ciltazol indiquant le pouvoir thérapeutique de ce médicament. De plus, la présente invention concerne l'effet supplémentaire de la thérapie du cilostazol et de l'atorvastatine contre l'ischémie due à l'augmentation de la signalisation de la phosphatodylicositol 3-kinase/AKT(PI3-/AKT), de la PKA et de la eNOS phosphorylée.
PCT/US2008/005026 2007-04-19 2008-04-18 Procédés d'augmentation des niveaux de camp et leurs utilisations WO2008130632A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US92534207P 2007-04-19 2007-04-19
US60/925,342 2007-04-19

Publications (2)

Publication Number Publication Date
WO2008130632A2 WO2008130632A2 (fr) 2008-10-30
WO2008130632A3 true WO2008130632A3 (fr) 2008-12-11

Family

ID=39876126

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/005026 WO2008130632A2 (fr) 2007-04-19 2008-04-18 Procédés d'augmentation des niveaux de camp et leurs utilisations

Country Status (1)

Country Link
WO (1) WO2008130632A2 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130131088A1 (en) * 2010-01-13 2013-05-23 University Health Network Treating cancer with statins and compounds having dipyridamole activity

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999026657A1 (fr) * 1997-11-25 1999-06-03 Musc Foundation For Research Development Inhibiteurs de la monoxyde d'azote-synthase

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999026657A1 (fr) * 1997-11-25 1999-06-03 Musc Foundation For Research Development Inhibiteurs de la monoxyde d'azote-synthase

Non-Patent Citations (24)

* Cited by examiner, † Cited by third party
Title
ATAR S. ET AL.: "Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2", AMERICAN JOURNAL OF PHYSIOLOGY - HEART AND CIRCULATORY PHYSIOLOGY, vol. 290, 2006, pages H1960 - H1968 *
BELL R.M. ET AL.: "Atorvastatin, Administerd at the Onset of Reperfusion, and Independent of Lipid Lowering, Protects the Myocardium by Up-Regulating a Pro-Survival Pathway", JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, vol. 41, no. 3, 2003, pages 508 - 515 *
BIRK S. ET AL.: "Analysis of the effects of phosphodiesterase type 3 and 4 inhibitors in cerebral arteries", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 489, 2004, pages 93 - 100 *
BIRNBAUM Y. ET AL.: "Reduction of Infarct Size by Short-Term Pretreatment with Atorvastatin", CARDIOVASCULAR DRUGS AND THERAPY, vol. 17, 2003, pages 25 - 30 *
BIRNBAUM Y. ETAL.: "Prostagladins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury", CARDIOVASCULAR RESEARCH, vol. 65, 2005, pages 345 - 355, XP004705727 *
CHAE H.-J. ET AL.: "Cyclic Adenosine Monophosphate Inhibits Nitric Oxide-Induced Apoptosis of Cardiac Muscle Cells in a c-Jun Terminal Kinase-Dependent Manner", IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY, vol. 26, no. 2, 2004, pages 249 - 263 *
CHANANI N.K. ET AL.: "Differential Effects of Amrinone and Milrinone Upon Myocardial Inflammatory Signaling", CIRCULATION, vol. 106, no. SUPPL. I, 2002, pages I-284 - I-289 *
EFTHYMIOU C.A. ET AL.: "Atorvastatin and myocardial reperfusion injury: new pleiotropic effect implicating multiple prosurvival signaling", JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 45, no. 3, 2005, pages 247 - 252 *
GERTZ K. ET AL.: "Withdrawal of statin treatment abrogates stroke protection in mice", STROKE, vol. 34, no. 2, 2003, pages 551 - 557 *
HAKAIM A.G. ET AL.: "Selective type III phosphodiesterase inhibition prevents elevated compartment pressure after ischemia/reperfusion injury", JOURNAL OF TRAUMA, vol. 46, no. 5, 1999, pages 869 - 872 *
HAUSENLOY D.J. ET AL.: "New directions for protecting the heart against ischemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway", CARDIOVASCULAR RESEARCH, vol. 61, 2004, pages 448 - 460, XP002407967 *
HOBBS S.D. ET AL.: "The effect of supervised exercise and cilostazol on coagulation and fibrinolysis intermittent claudication: A randomized controlled trial", JOURNAL OF VASCULAR SURGERY, vol. 45, no. 1, January 2007 (2007-01-01), pages 65 - 70, XP005821236 *
HONG H. ET AL.: "Atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in ischemic stroke", AMERICAN JOURNAL OF PHYSIOLOGY - HEART AND CIRCULATORY PHYSIOLOGY, vol. 291, 2006, pages H2210 - H2215 *
HONG K.W. ET AL.: "Cilostazol: Therapeutic Potential Against Focal Cerebral Ischemic Damage", CURRENT PHARMACEUTICAL DESIGN, vol. 12, no. 5, 2006, pages 565 - 573 *
LAUFS U. ET AL.: "Atorvastatin Upregulates Type III Nitric Oxide Synthase in Thrombocytes, Decreases Platelet Activation, and Protects From Cerebral Ischemia in Normocholesterolemic Mice Editorial Comment", STROKE, vol. 31, 2000, pages 2442 - 2449 *
LAUFS U. ET AL.: "Rosuvastatin, a novel HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice", BRAIN RESEARCH, vol. 942, 2002, pages 23 - 30 *
LEE J.H. ET AL.: "Cilostazol Prevents Focal Cerebral Ischemia Injury by Enhancing Casein Kinase 2 Phosphorylation and Suppression of Phosphatase and Tensin Homolog Deleted from Chromosome 10 Phosphorylation in Rats", THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 308, no. 3, 2004, pages 896 - 903 *
LEE J.H. ET AL.: "Cilostazol reduces brain lesion induce by focal cerebral ischemia in rats-an MRI study", BRAIN RESEARCH, vol. 994, 2003, pages 91 - 98 *
LEE J.H. ET AL.: "Neuroprotective Effect of Cilostazol against Focal Cerebral Ischemia via Antiapoptotic Action in Rats", THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 300, no. 3, 2002, pages 787 - 793 *
MENSAH K. ET AL.: "Failure of Protect the Myocardium Against Ischemia/Reperfusion Injury After Chronic Atorvastatin Treatment Is Recaptured by Acute Atorvastatin Treatment - A potential role for phosphatase and tensin homolog deleted on chromosome ten?", JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, vol. 45, no. 8, 2005, pages 1287 - 1291, XP004851914 *
NISHIMATSU H. ET AL.: "Endothelial dysfunction and hypercontractility of vascular myocytes are ameliorated by fluvastatin in obese Zucker rats", AMERICAN JOURNAL OF PHYSIOLOGY - HEART AND CIRCULATORY PHYSIOLOGY, vol. 288, 2005, pages H1770 - H1776 *
OZACMAK V.H. ET AL.: "Attenuation of contractile dysfunction by atorvastatin after intestinal ischemia reperfusion injury in rats", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 562, 2007, pages 138 - 147, XP022004270 *
YE Y. ET AL.: "Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanism and possible interactions", AMERICAN JOURNAL OF PHYSIOLOGY - HEART AND CIRCULATORY PHYSIOLOGY, vol. 291, 2006, pages H1158 - H1169 *
ZHAI W. ET AL.: "Ischemia/reperfusion injury: the role of CD26/dipeptidyl-peptidase-iv-inhibition in lung transplantation", TRANSPLANTATION PROCEEDINGS, vol. 38, no. 10, 2006, pages 3369 - 3371, XP005804042 *

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