Methods For Avoiding Edema in the Treatment of Metabolic, Inflammatory, and Cardiovascular Disorders

Abstract

Compounds, compositions, and methods of treating or preventing PPARγ-mediated diseases, including cancer, using phenoxy acetic acid derivatives and prodrugs are provided.

Description

[0001]This application claims benefit under 35 U.S.C. §112(e) of U.S. Provisonal Application Ser. No. 60 / 663,977, filed Mar. 21, 2005, and of U.S. Provisional Application Ser. No. 60 / 664,515 filed Mar. 22, 2005, the disclosure of each of which is incorporated herein in its entirety for all purposes to the extent not inconsistent with the present disclosure. This application is related in subject matter to a PCT application of the same inventorship and assignment as the present application, entitled “Methods for Avoiding Edema in the Treatment or Prevention of PPARγ-Responsive Diseases, including Cancer,” filed Mar. 21, 2006 (Attorney-Client Matter No. 016325-020210PC), which is incorporated herein by reference.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT[0002]NOT APPLICABLEREFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED ON A COMPACT DISKBACKGROUND OF THE INVENTION[0003]Peroxisome proliferato...

AI Technical Summary

Benefits of technology

[0041]In yet another embodiment, the invention provides a method for preventing peripheral edema, ascites, cardiac enlargement, excess body fluid retention, or pulmonary edema in a subject having a metabolic or cardiovascular disorder by administering to a subject in need thereof a compound of any one of Formula I, II, III, IVa, IVb, V, VI, or VII. In a further embodiment, the edema was not caused or exacerbated by administration of insulin or an insulin sensitizer or another anti-diabetic agent to the subject. In another embodiment, the edema was caused or exacerbated by administration of an insulin or an insulin sensitizer or another anti-diabetic agent to the subject.

[0048]In another aspect, the invention provides methods of providing a beneficial hemodynamic effect. In some embodiments, the invention provides a method of lowering systolic and diastolic blood pressure and to reduce cardiac afterload. In addition, the invention provides methods of reducing intravascular volume and the cardiac preload. In other embodiments, the invention provides a means of increasing cardiac output and / or increasing renal blood flow without an increase in heart rate. In addition, the invention provides a method of reducing cardiovascular mortality by improving hemodynamics. These effects can be accomplished by administering therapeutic amounts of PPARγ partial agonists and compounds of formulae I, II, III, IVa, IVb, V, VI, or VII.

Problems solved by technology

Subjects with elevated C-reactive protein levels are at an increased risk of cerebrovascular and cardiovascular events thromboembolism, myocardial infarction (MI) and cerebrovascular accident (CVA).

The risk of edema may be evidenced by a prior history of edema or by co-administration of a drug which is capable of causing edema.

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