- New fatty acid oxidation inhibitors with increased potency lacking adverse metabolic and electrophysiological properties
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New inhibitors of palmitoylCoA oxidation were synthesized based on a structurally novel lead, CVT-3501 (1). Investigation of structure-activity relationships was conducted with respect to potency of inhibition of cardiac mitochondrial palmitoylCoA oxidation and metabolic stability. Potent and metabolically stable analogues 33, 42, and 43 were evaluated in vitro for cytochrome P450 inhibition and potentially adverse electrophysiological effects. Compound 33 was also found to have favorable pharmacokinetic properties in rat.
- Koltun, Dmitry O.,Marquart, Timothy A.,Shenk, Kevin D.,Elzein, Elfatih,Li, Yuan,Nguyen, Marie,Kerwar, Suresh,Zeng, Dewan,Chu, Nancy,Soohoo, Daniel,Hao, Jia,Maydanik, Victoria Y.,Lustig, David A.,Ng, Khing-Jow,Fraser, Heather,Zablocki, Jeffery A.
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Read Online
- Substituted heterocyclic compounds
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Disclosed are novel piperazine derivatives, useful for the treatment of various disease states, in particular diseases such as atrial and ventricular arrhythmias, diabetes, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angi
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Page/Page column 15
(2008/06/13)
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- UREA DERIVATIVES OF PIPERAZINES AND PIPERIDINES AS FATTY ACID OXIDATION INHIBITORS
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Disclosed are novel piperazine derivatives, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable
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Page/Page column 40
(2008/06/13)
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- 1-AKAN-2-OL SUBSTITUTED PIPERAZINE AND PIPERIDINE COMPOUNDS
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Disclosed are novel substituted heterocyclic derivatives having the structure of Formula (I): The compounds are useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermitt
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Page/Page column 42
(2008/06/13)
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- Substituted heterocyclic compounds
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Disclosed are novel heterocyclic derivatives, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes, and for increasing HDL plasma levels in mammals.
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- Novel inhibitors of fatty acid oxidation as potential metabolic modulators
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We describe the synthesis of novel inhibitors of fatty acid oxidation as potential metabolic modulators for the treatment of stable angina. Replacement of the 2H-benzo[d]1,3-dioxolene ring system in our initial lead 3 with different benzthiazoles, benzoxa
- Elzein, Elfatih,Shenk, Kevin,Ibrahim, Prabha,Marquart, Tim,Kerwar, Suresh,Meyer, Stephanie,Ahmed, Hiba,Zeng, Dewan,Chu, Nancy,Soohoo, Daniel,Wong, Shirley,Leung, Kwan,Zablocki, Jeff
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p. 973 - 977
(2007/10/03)
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS USEFUL IN THE TREATMENT OF CARDIOVASCULAR DISEASES
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wherein: a.o. T is oxygen, sulfur, or NR11 , in which R11 is hydrogen or lower alkyl; V is -N1 is hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; X2 is optionally substituted aryl or optionally substituted heteroaryl; Y is optionally substituted dihydroheteroarcyl; and Z1 and Z2 are independently optionally substituted alkylene of 1-4 carbon atoms, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal’s (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes.
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- Substituted heterocyclic compounds
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Disclosed are novel heterocyclic derivatives, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes, and for increasing HDL plasma levels in mammals.
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