Syntex Pharmaceuticals, Ltd.

Syntex (u.s.a.) Inc.

Syntex Pharmaceutical Ltd.

Robert J Dow

Henri Pinhas

Roger L Whiting

Serge Beranger

Brian J Alps

Jean C Pascal

Chi-Ho Lee

Calum B Macfarlane

Pierre Ferrandon

Piperazine derivatives, particularly ranolazine, are useful for treatment of tissues experiencing a physical or chemical insult, and specifically for treating cardioplegia, hypoxic and/or reperfusion injury to cardiac or skeletal muscle or brain tissue, and for use in transplants.

Methods of treatment using ranolazine and related piperazine derivatives

Substituted imidazolyl-alkyl-piperazine and diazepine derivatives and the pharmaceutically acceptable salts thereof are useful for treating mammals having any of a variety of disease states. These disease states include: 1) diseases treated by direct neuronal protection, including focal and global ischemia, spinal injuries, and head trauma, and neurological diseases including Alzheimer's and Huntington's chorea; 2) uraemic and hyponatraemic encephalopathy; 3) diseases treated by diuresis; 4) diseases treated by calcium channel antagonism, including cardiovascular diseases (i.e. hypertension, angina, stable and unstable angina, Prinzmetal angina, arrhythmia, thrombosis, embolism, and congestive heart failure including chronic or acute cardiac failure), diseases characterized by ischemia of lower legs due to peripheral vascular disease (e.g., intermittent claudication), diseases characterized by spasms of smooth muscle (i.e., spasms of the ureter, spasms of the bladder, uterine cramps, and irritable bowel syndrome), and prevention of vasoconstriction and/or ischemic tissue damage during a surgical procedure (i.e., bypass grafts, angiography, angioplasty, organ preservation during transplant, hypertensive crisis or post operative hypertension).

Substituted imidazolyl-alkyl-piperazine and -diazepine derivatives

Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: ##STR1## wherein: R.sup.1 is aryl, lower alkyl, cycloalkyl or hydrogen;

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Edinburgh, United Kingdom

Robert J Dow