Zhen M Cheng

US Patent:

7704990, Apr 27, 2010

Filed:

Aug 25, 2005

Appl. No.:

11/212413

Inventors:

Donald W. Landry - New York NY, US
Shixian Deng - White Plains NY, US
Zhen Zhuang Cheng - Elmhurst NY, US

Assignee:

The Trustees of Columbia University in the City of New York - New York NY

International Classification:

C07D 281/02
A61K 31/554

US Classification:

51421105, 51421109, 540490, 540552

Abstract:

The present invention provides novel compounds of Formula I.

US Patent:

7718644, May 18, 2010

Filed:

Mar 25, 2004

Appl. No.:

10/809089

Inventors:

Andrew Robert Marks - Larchmont NY, US
Donald W. Landry - New York NY, US
Shixian Deng - White Plains NY, US
Zhen Zhuang Cheng - Elmhurst NY, US

Assignee:

The Trustees of Columbia University in the City of New York - New York NY

International Classification:

A01N 43/00
A61K 31/00

US Classification:

51421105, 540552

Abstract:

The present invention provides methods for limiting or preventing a decrease in the level of RyR2-bound FKBP12. 6 in a subject. The present invention further provides methods for treating and preventing atrial and ventricular cardiac arrhythmias, heart failure, and exercise-induced sudden cardiac death in a subject. Additionally, the present invention provides use of JTV-519 in a method for limiting or preventing a decrease in the level of RyR2-bound FKBP12. 6 in a subject who has, or is a candidate for, atrial fibrillation. Also provided are uses of 1,4-benzothiazepine derivatives in methods for treating and preventing atrial and ventricular cardiac arrhythmias and heart failure in a subject, and for preventing exercise-induced sudden cardiac death. The present invention also provides methods for identifying agents for use in treating and preventing atrial fibrillation and heart failure, and agents identified by these methods.

US Patent:

20040229781, Nov 18, 2004

Filed:

Oct 7, 2003

Appl. No.:

10/680988

Inventors:

Andrew Marks - Larchmont NY, US
Donald Landry - New York NY, US
Shi Deng - White Plains NY, US
Zhen Cheng - Elmhurst NY, US

International Classification:

A61K038/17

US Classification:

514/012000

Abstract:

The present invention provides a method for limiting or preventing a decrease in the level of RyR2-bound FKBP12.6 in a subject, a method for treating or preventing exercise-induced cardiac arrhythmia in a subject, and a method for preventing exercise-induced sudden cardiac death in a subject. Also provided are uses of JTV-519 in these methods. The present invention further provides methods for identifying agents for use in preventing exercise-induced sudden cardiac death, as well as agents identified by such methods. Also provided are methods for preventing exercise-induced sudden cardiac death by administering these agents. Additionally, the present invention provides methods for synthesizing JTV-519, radio-labeled JTV-519, and 1,4-benzothiazepine intermediates and derivatives.

US Patent:

20050186640, Aug 25, 2005

Filed:

Mar 23, 2005

Appl. No.:

11/088123

Inventors:

Andrew Marks - Larchmont NY, US
Donald Landry - New York NY, US
Shi Deng - White Plains NY, US
Zhen Cheng - Elmhurst NY, US

International Classification:

G01N033/53
G01N033/567

US Classification:

435007200

Abstract:

The present invention provides novel 1,4-benzothiazepine intermediates and derivatives, methods for synthesizing same, and methods for assaying same. The present invention also provides methods for using these novel compounds to limit or prevent a decrease in the level of RyR2-bound FKBPl2.6 in a subject; to prevent exercise-induced sudden cardiac death in a subject; and to treat or prevent heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia in a subject. The present invention further provides methods for identifying an agent that enhances binding of RyR2 and FKBP12.6, and agents identified by these methods. Additionally, the present invention provides methods for identifying agents for use in treating or preventing heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia, and in preventing exercise-induced sudden cardiac death. Also provided are agents identified by such methods.

US Patent:

20050187386, Aug 25, 2005

Filed:

Mar 23, 2005

Appl. No.:

11/088058

Inventors:

Andrew Robert Marks - Larchmont NY, US
Donald Landry - New York NY, US
Shi Xian Deng - White Plains NY, US
Zhen Zhuang Cheng - Elmhurst NY, US

International Classification:

C07D267/02

US Classification:

540546000

Abstract:

The present invention provides novel 1,4-benzothiazepine intermediates and derivatives, methods for synthesizing same, and methods for assaying same. The present invention also provides methods for using these novel compounds to limit or prevent a decrease in the level of RyR2-bound FKBP12.6 in a subject; to prevent exercise-induced sudden cardiac death in a subject; and to treat or prevent heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia in a subject. The present invention further provides methods for identifying an agent that enhances binding of RyR2 and FKBP12.6, and agents identified by these methods. Additionally, the present invention provides methods for identifying agents for use in treating or preventing heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia, and in preventing exercise-induced sudden cardiac death. Also provided are agents identified by such methods.

US Patent:

20060194767, Aug 31, 2006

Filed:

Aug 25, 2005

Appl. No.:

11/212309

Inventors:

Andrew Marks - Larchmont NY, US
Donald Landry - New York NY, US
Shixian Deng - White Plains NY, US
Zhen Cheng - Elmhurst NY, US
Stephan Lehnart - New York NY, US

Assignee:

THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK - New York NY

International Classification:

A61K 31/675
A61K 31/655
C07D 291/08
C07D 417/02

US Classification:

514081000, 514211090, 514151000, 540552000

Abstract:

The present invention provides novel compounds of Formula I and salts, hydrates, solvates, complexes, and prodrugs thereof. The present invention further provides methods for synthesizing compounds of Formula I. The invention additionally provides pharmaceutical compositions comprising the compounds of Formula I and methods of using the pharmaceutical compositions of Formula I to treat and prevent disorders and diseases associated with the RyR receptors that regulate calcium channel functioning in cells. Such disorders and diseases include, by way of example only, cardiac disorders and diseases, skeletal muscular disorders and diseases, cognitive disorders and diseases, malignant hyperthermia, diabetes, and sudden infant death syndrome. Cardiac disorder and diseases include, but are not limited to, irregular heartbeat disorders and diseases; exercise-induced irregular heartbeat disorders and diseases; sudden cardiac death; exercise-induced sudden cardiac death; congestive heart failure; chronic obstructive pulmonary disease; and high blood pressure. Irregular heartbeat disorders and diseases include and exercise-induced irregular heartbeat disorders and diseases include, but are not limited to, atrial and ventricular arrhythmia; atrial and ventricular fibrillation; atrial and ventricular tachyarrhythmia; atrial and ventricular tachycardia; catecholaminergic polymorphic ventricular tachycardia (CPVT); and exercise-induced variants thereof. Skeletal muscular disorder and diseases include, but are not limited to, skeletal muscle fatigue, exercise-induced skeletal muscle fatigue, muscular dystrophy, bladder disorders, and incontinence. Cognitive disorders and diseases include, but are not limited to, Alzheimer's Disease, forms of memory loss, and age-dependent memory loss.

US Patent:

20090292119, Nov 26, 2009

Filed:

Oct 31, 2008

Appl. No.:

12/263435

Inventors:

Donald W. Landry - New York NY, US
Shixian Deng - White Plains NY, US
Zhen Z. Cheng - Elmhurst NY, US

Assignee:

THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK - New York NY

International Classification:

C07D 417/02
C07D 285/36
C07D 413/02

US Classification:

540552

Abstract:

The present invention provides improved methods for synthesizing novel benzothiazepine compounds. In particular, the invention relates to a new method that generally is used to make the substituted 2,3,4,5-tetrahydro-1,4-benzothiazepine compounds of a general formulawhich then may be used to make many other benzothiazepine compounds.

US Patent:

20100152440, Jun 17, 2010

Filed:

Jun 8, 2009

Appl. No.:

12/480396

Inventors:

Andrew Robert Marks - Larchmont NY, US
Donald W. Landry - New York NY, US
Shi Xian Deng - White Plains NY, US
Zhen Zhuang Cheng - Elmhurst NY, US

International Classification:

C07D 417/06
C07D 281/08

US Classification:

540552

Abstract:

The present invention provides novel 1,4-benzothiazepine intermediates and derivatives, methods for synthesizing same, and methods for assaying same. The present invention also provides methods for using these novel compounds to limit or prevent a decrease in the level of RyR2-bound FKBP12.6 in a subject; to prevent exercise-induced sudden cardiac death in a subject; and to treat or prevent heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia in a subject. The present invention further provides methods for identifying an agent that enhances binding of RyR2 and FKBP12.6, and agents identified by these methods. Additionally, the present invention provides methods for identifying agents for use in treating or preventing heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia, and in preventing exercise-induced sudden cardiac death. Also provided are agents identified by such methods.