E. R. Squibb Sons, Inc.

Bristol-myers Squibb Compnay

Atwal, Karnail

Grover, Gary J.

Kim, Kyoung S.

Gary J Grover

Karnail S Atwal

James L Bergey

William A Schumacher

John Krapcho

Saleem Ahmad

David L Green

John E Lloyd

Kyoung S Kim

Philip D Stein

Charles Z Ding

Lawrence Friedhoff

Martin L Ogletree

Francis N Ferrara

John R McCullough

Albert J D'Alonzo

Irvin E Fulmor, Iii

Lawrnce G Hamann

Compounds having the formula (I), and pharmaceutically acceptable salts thereof,are useful for modulating mitochondrial FFATPase activity and treating ischemic conditions including myocardial infarction, congestive heart failure, and cardiac arrhythmias.

(1-phenyl-2-heteoaryl)ethyl-guanidine compounds as inhibitors of mitochondrial F1F0 ATP hydrolase

A method for the concomitant treatment of ischemia and arrhythmia in mammalian species which includes administering a combination of a potassium channel opener having little or no effect on action potential duration in the heart and a class III antiarrhythmic compound.

Combination of a potassium channel activator and an antiarrhythmic agent

In accordance with the present invention novel methods for cardiopulmonary bypass and organ transplant, each employing a potassium channel activator, are disclosed. The use of a potassium channel activator has been found to reduce the damage or ischemia induced by the bypass and transplant procedures.

Cardiopulmonary bypass and organ transplant using a potassium channel

A method is provided for inhibiting myocardial cell necrosis and improving myocardial function during myocardial ischemia and/or reperfusion by locally administering to the heart a potent potassium channel activator such as pinacidil or cromakalim.

Method for inhibiting myocardial cell necrosis and preserving heart

A method for the treatment and prevention of fibrillation using one or more potassium channel activators. Also, disclosed is a process for the preparation of compounds of the formula ##STR1## and the tautomeric forms ##STR2## wherein R''and R' are as defined herein.

Method of treating or prevention of fibrillation of the heart

A method is provided for treating ischemia in a mammalian species by administering a combination of a calcium channel blocker such as diltiazem, SQ 31,765 or SQ 32,324 and a thromoboxane A.sub.2 receptor antagonist such as SQ 30,741 or a thromboxane synthetase inhibitor such as dazoxiben.

Combination of a calcium channel blocker and thromboxane A.sub.2

Novel compounds having the formula ##STR1## wherein ##STR2## are disclosed. These compounds have potassium channel activating activity and are useful, for example, as cardiovascular agents, especially as antiischemic agents.

Pyranyl cyanoguanidine derivatives

A novel pharmaceutical composition and method is disclosed for the treatment of cardiovascular diseases, e.g. myocardial ischemia and/or arrhythmia. The method and composition include an effective amount of a compound of the formula ##STR1## wherein X, Y, R, R.sub.1, A, A', m, n, p, p' and B are as defined herein.

Pharmaceutical composition and method for treating cardiovascular

A method is provided for preventing reducing or reversing adverse reactions, such as pulmonary hypertension produced when protamine interacts with heparin, by administering a thromboxane A.sub.2 receptor antagonist.

Method of preventing or reducing adverse reactions to protamine using a

Novel compounds of the formula ##STR1## and tautomers thereof, wherein at least one of R.sub.2, R.sub.3 and R.sub.4 is a strong electron withdrawing group, are disclosed. These compounds possess potassium channel activating activity and, as such, are useful as antihypertensive agents. Advantageously, the compounds of the present invention have shown less cardiac effects than known potassium channel activators. Also disclosed is a process for preparing these and other compounds.

Aryl cyanoguanidines: potassium channel activators and method of making

Zofenopril, fosinopril, (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-pro line or a pharmaceutically acceptable salt thereof alone or in combination with a thrombolytic, antiarrhythmic, or antifibrillatory agent is employed to reduce pre- and post-ischemic myocardial arrhythmias and fibrillations as well as reducing arrhythmias associated with congestive heart failure.

Method of reducing pre- and post-ischemic myocardial arrhythmias and

A method is provided for improving post-ischemic myocardial function such as contractile dysfunction or reperfusion injury by administering a thromboxane receptor antagonist which is a 7-oxabicycloheptane substituted diamide prostaglandin analog in combination with a thrombolytic agent before, during or immediately after an ischemic attack.

Method of improving post-ischemic myocardial function using a

Zofenopril, fosinopril, (S)-1-[6-amino-2-[[hydroxy (4-phenylbutyl) phosphinyl]oxy]-1-oxohexyl]-L-proline or a pharmaceutically acceptable salt thereof alone or in combination with a thrombolytic, antiarrhythmic, or antifibrillatory agent is employed to reduce pre-and post- ischemic myocardial arrhythmias and fibrillations as well as reducing arrhythmias associated with congestive heart failure.

Method of reducing pre-and post-ischemic myocardial arrhythmias and

Zofenopril, fosinopril, (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-oxohexyl]-L-proli ne or a pharmaceutically acceptable salt thereof alone or in combination with a thrombolytic, antiarrhythmic, or antifibrillatory agent is employed to reduce pre- and post- ischemic myocardial arrhythmias and fibrillations as well as reducing arrhythmias associated with congestive heart failure.

Growing community of inventors

Stockton, NJ, United States of America

Gary J Grover