Laroche Navarron S.a.

Syntex Pharmaceuticals, Ltd.

Serdex-societe D'etudes, De Recherches, De Diffusion Et D'exploitation

Laboratoires Syntex

Recherche Syntex

Syntex Pharmaceutical Ltd.

Serge Beranger

Henri Pinhas

Roger L Whiting

Jean-Claude G Pascal

Jean C Pascal

Brian J Alps

Chi-Ho Lee

Colette Favier

Calum B Macfarlane

Robert J Dow

Bruno Francois

J Claude Pascal

Isabelle Jullien

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).

Aryl- and heterocyclic-methanamines are prepared by reacting a hydroxy-aryl carbinol or a heterocyclic carbinol with a primary or a secondary amine in the presence of a cationic effect reagent.

Cationic effect-driven carbinol/amine reaction

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

New compounds of formulas I and II ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein M is selected from the group consisting of hydrogen, morpholino, benzylamino, di-n-lower alkylamino, n-lower alkylamino and ##STR2## wherein Ar is optionally substituted phenyl; Z.sub.1 and Z.sub.2 are each independently selected from the group consisting of CH.sub.2, CHOB and C.dbd.O, wherein B is selected from the group consisting of hydrogen and alkanoyl;

Piperazine derivatives of theophylline and theobromine

New compounds of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein M is selected from the group consisting of hydrogen, morpholino, benzylamino, di-n-lower alkylamine, n-lower alkylamine, and aryl piperazino;

Piperazine derivatives of theophylline

New compounds of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein Z.sub.1 and Z.sub.2 are each independently selected from the group consisting of CH.sub.2, CHOB and C.dbd.O, wherein B is selected from the group consisting of hydrogen and alkanoyl;

Piperazine derivatives of theobromine

The present invention relates to compounds of the general formula: ##STR1## in which: R.sub.1 is selected from hydrogen and alkoxy having 1-7 carbon atoms,

Chromene derivatives useful as bronchodilators and anti-arrhythmics

The present invention provides compounds of formula: ##STR1## wherein R.sub.1 is selected from the group consisting of hydrogen, halog alkyl having from 1 to 6 carbon atoms, alcoxy having from 1 to 6 carbon atoms and alkylthio having from 1 to 6 carbon atoms, A taken separately is hydrogen and B is a radical with the formula ##STR2## , R.sub.3 being selected from the group consisting of hydrogen, halogen and alcoxy having from 1 to 6 carbon atoms, and A and B taken together form a radical --O--CH.sub.2 --, and the esters, N oxides and pharmacologically acceptable salts of the acids of Formula I. These compounds have analgesic and antiinflammatory properties.

Growing community of inventors

Bretigny-Sur-Orge, France

Serge Beranger