The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Apr. 05, 2016

Filed:

Jul. 23, 2014
Applicants:

University of Connecticut, Farmington, CT (US);

The United States of America, As Represented BY the Secretary, Department of Health and Human Serivces, Washington, DC (US);

Inventors:

Bruce Liang, Avon, CT (US);

Kenneth A. Jacobson, Silver Spring, MD (US);

Assignee:

UNIVERSITY OF CONNECTICUT, Farmington, CT (US);

Attorney:
Primary Examiner:
Assistant Examiner:
Int. Cl.
CPC ...
C07F 9/6561 (2006.01); A61K 31/675 (2006.01);
U.S. Cl.
CPC ...
C07F 9/65616 (2013.01); A61K 31/675 (2013.01);
Abstract

Phosphonate and phosphinate N-methanocarba derivatives of AMP including their prodrug analogs are described. MRS2339, a 2-chloro-AMP derivative containing a (N)-methanocarba(bicyclo[3.1.0]hexane) ring system in place of ribose, activates P2X receptors, ligand-gated ion channels. Phosphonate analogues of MRS2339 were synthesized using Michaelis-Arbuzov and Wittig reactions, based on the expectation of increased half-life in vivo due to the stability of the C—P bond. When administered to calsequestrin-overexpressing mice (a genetic model of heart failure) via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in vivo, as assessed by echocardiography-derived fractional shortening (FS) as compared to vehicle-infused mice. The range of carbocyclic nucleotide analogues for treatment of heart failure has been expanded.


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