Substituted heterocyclic compounds
AssigneeCV Therapeutics, Inc.
InventorsPrabha Ibrahim, Kevin Shenk, Elfatih Elzein, Venkata Palle, Jeff Zablocki, Kenneth S. Rehder
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Abstract
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.
Claims29
A compound of the formula:
- 39
- wherein:
- R1, R2, R3, R4, R5, R6, R7, and R8 are hydrogen, lower alkyl, or —C(O)R;
- in which R1 is —OR9 or NR9R10, where R9 and R10 are hydrogen or lower alkyl;
- or
- R1 and R2, R3 and R4, R5 and R6, R7 and R8, when taken together with the carbon to which they are attached, represent carbonyl;
- or
- R1 and R5, or R1 and R7, or R3 and R5, or R3 and R7, when taken together form a bridging group —(CR12R13)n—, in which n is 1, 2 or 3, and R12 and R13 are independently hydrogen or lower alkyl;
- with the provisos that
- i. the maximum number of carbonyl groups is 2;
- ii. the maximum number of —C(O)NR9R10 groups is 1;
- and
- iii. the maximum number of bridging groups is 1;
- T is oxygen, sulfur, or NR11, in which R11 is hydrogen or lower alkyl;
- V is —N<, —CH<, or —N—CH<;
- X1 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 monocyclic heteroarylenyl;
- and
- Z1 and Z2 are independently optionally substituted alkylene of 1-4 carbon atoms.
25 A method of treating a disease state chosen from diabetes, damage to skeletal muscles resulting from trauma or shock and a cardiovascular disease in a mammal by administration of a therapeutically effective dose of a compound of claim 1.
The method of claim 25, wherein the cardiovascular disease is atrial arrhythmia, intermittent claudication, ventricular arrhythmia, Prinzmetal's (variant) angina, stable angina, unstable angina, congestive heart disease, or myocardial infarction.
The method of claim 25, wherein the disease state is diabetes.
29 A method of preserving donor tissue and organs used in transplants, comprising administering to a mammal in need thereof a therapeutically effective dose of a compound of claim 1.
Dependencies are inferred from the claim text.