G.d. Searle & Company

Other

Continental Pharma Incorporated

Alexis A Cordi

Claude L Gillet

Michael L Vazquez

Joseph L Roba

Georges E Lambelin

William R Van Dorsser

Roberto Pellicciari

Michel R Franz

Paul J Niebes

Hugo J Gorissen

Michel P Snyers

Thomas H Lanthorn

Maura Marinozzi

Benedetto Natalini

Robert G Cavalier

Philippe M Janssens De Varebeke

Piedad Calderon

A class of phosphono-hydroisoquinoline compounds is described for treatment to reduce neurotoxic injury associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a phosphono-hydroisoquinoline compound alone or in a composition in an amount effective as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of the formula: ##STR1## wherein each of R.sup.1 through R.sup.4 is hydrido, each of Z.sup.1 and Z.sup.2 is hydroxyl and wherein the A ring is saturated.

Phosphono-hydroisoquinoline compounds useful in reducing neurotoxic

A class of diphenylmethylaminoacetamide derivatives is described having use in treatment of CNS dysfunctions such as epilepsy and convulsive disorders. Compounds of most interest are those of the formula ##STR1## wherein each of X and Y is independently selected from hydrido and halo; and wherein each of R.sup.1, R.sup.2 and R.sup.3 is hydrido; or a pharmaceutically-acceptable salt thereof.

Diphenylmethylaminoacetamide derivatives as anti-convulsants

Compounds, compositions and methods are described for treating a CNS disorder such as a cognitive disorder, epilepsy, depression, Parkinson's disease, Alzheimer's disease, a neurodegenerative disease or neurotoxic injury. Compound of interest are 2-amino-4,5-methyleneadipic acid compounds and derivatives defined by the formula I: ##STR1## wherein R.sup.1 is selected from hydrido, alkyl, cycloalkyl, aralkyl, aryloxyalkyl, arylthioalkyl, ##STR2## with each of R.sup.2, R.sup.3, R.sup.4 and R.sup.5 being independently selected from hydrido, alkyl, cycloalkyl, aryl and aralkyl; wherein each of X and Y is independently selected from hydroxyl, alkoxy, alkylthio, amino and ##STR3## with each of R.sup.6 and R.sup.7 being independently selected from hydrido, alkyl, cycloalkyl, aryl and aralkyl; wherein any of R.sup.1 through R.sup.7 groups having a substitutable position may be substituted with one or more substituents selected from hydroxyl, halo, alkyl, haloalkyl, cyano, alkoxy, alkylthio, sulfinyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, amino, acyl, acyloxy, alkoxycarbonyl and aminocarbonyl; or a pharmaceutically-acceptable salt thereof.

2-amino-4,5-methyleneadipic acid compounds for treatment of CNS disorders

A class of phosphono-hydroisoquinoline compounds is described for treatment to reduce neurotoxic injury associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a phosphono-hydroisoquinoline compound alone or in a composition in an amount effective as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of Formula I: ##STR1## wherein each of R.sup.1 through R.sup.4 is hydrido, wherein each of Z.sup.1 and Z.sup.2 is hydroxyl, wherein W is a single bond connecting the phosphorus atom with the aromatic ring and wherein the A ring is aromatic. Also disclosed are two classes of intermediate compounds having a fully unsaturated A ring, which intermediate compounds are useful in methods to make product compounds of Formula I.

o-Phosphono(alkyl)-N-sulfonyl-phenyl-alanine derivatives useful as

A class of tricyclic glycinamide derivatives is described having use in treatment of CNS dysfunctions such as epilepsy and convulsive disorders. Compounds of most interest are those of the formula ##STR1## wherein each of X and Y is hydrido; wherein Z is selected from methylene, ethylene, ethenylene, thiomethylene and thioethylene; and wherein each of R.sup.1, R.sup.2 and R.sup.3 is hydrido; or a pharmaceutically-acceptable salt thereof.

Tricyclic glycinamide derivatives as anti-convulsants

A class of phosphono-hydroisoquinoline componds is described for treatment to reduce neurotoxic injury associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a phosphono-hydroisoquinoline compound alone or in a composition in an amount effective as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of the formula: ##STR1## wherein each of R.sup.1 through R.sup.4 is hydrido, each of Z.sup.1 and Z.sup.2 is hydroxyl and wherein the A ring is aromatic.

A compound of the formula: ##STR1## wherein X.sup.1, X.sup.2, Y.sup.1 and Y.sup.2, whether or not identical are hydrogen, a halogen such as fluoro, chloro or bromo, linear or branched alkyl of 1 to 3 carbon atoms, linear or branched alkoxy of 1 to 3 carbon atoms, carboxy, alkoxy-carbonyl of 1 to 3 carbon atoms or phenyl;

.alpha..sub.2 -blocking derivatives of imidazole

2-Pentanoylaminoacetic acid and pharmaceutically suitable salts thereof are claimed for use as pharmaceuticals. The compounds are useful in producing an effect on the central nervous system, especially in the treatment of various forms of epilepsy, of disninesiae, of parkinsonism, of memory troubles, of psychic troubles and of cerebral anoxia.

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St. Louis, MO, United States of America

Alexis A Cordi