Syntex Pharmaceuticals, Ltd.

Laroche Navarron S.a.

Syntex Pharmaceutical Ltd.

Jean C Pascal

Henri Pinhas

Roger L Whiting

Chi-Ho Lee

Brian J Alps

Serge Beranger

Calum B Macfarlane

Robert J Dow

Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, m, n and q are defined as in the specification, and the pharmaceutically acceptable salts thereof. The compounds have calcium entry blocking activity with selectivity for cerebral blood vessels, and have protective activity against some of the deleterious effects resultant upon cerebral ischemia.

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

Sustituted imidazolyl-alkyl-piperazine and -diazepine derivatives for

The invention relates to compounds having the formula: ##STR1## in which: the substituents R.sub.1, R.sub.2 and R.sub.3 represent independently from each other a hydrogen atom, a halogen atom, a trifluoromethyl radical, a saturated or unsaturated straight- or branched-chain C.sub.1-6 alkyl radical, a C.sub.1-6 alkoxy radical the alkyl moiety of which may be saturated or unsaturated and straight- or branched-chained, a benzyloxy radical or a hydroxy radical; the substituents R.sub.5, R.sub.6 and R.sub.7 represent independently from each other a hydrogen atom, a halogen atom, a trifluoromethyl radical, a straight- or branched-chain saturated or unsaturated C.sub.1-6 alkyl radical, a C.sub.1-6 alkoxy radical the alkyl moiety of which may be saturated or unsaturated and straight- or branched-chained, or a hydroxy radical; the substituent R.sub.4 represents a hydrogen atom, a C.sub.1-6 alkyl radical or a hydroxy radical, m and n represent independently a number equal to 0, 1 or 2, X represents an oxygen atom, a sulfur atom or a single bond, and their pharmaceutically acceptable acid addition salts. These compounds are therapeutically useful for the control of the cardiovascular system.

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Cachan, France

Jean C Pascal