The Dupont Merck Pharmaceutical Company

E.i. Dupont De Nemours and Company

Wendell W Wilkerson

Richard A Earl

Christopher A Teleha

Matthew Ernst Voss

James David Rodgers

Paul R Hartig

Peter John Gillies

Jeffrey T Billheimer

Robert Zaczek

Simon Piers Aiken

Barry Stephen Brown

Compounds of Formula (I) have been shown to enhance the release of the neurotransmitter acetylcholine, and thus may be useful in the treatment of diseases of man where subnormal levels of this neurochemical are found, such as in Alzheimer's disease, and other conditions involving learning and cognition. This invention describes compounds, pharmaceutical compositions and methods of treatment comprising compounds of Formula (I): ##STR1##

Polycyclic systems, and derivatives thereof, as neurotransmitter release

Compounds which block neuronal M-channels are useful for treating conditions involving neurotransmitter deficiencies, traumatic brain injury, or the depressive phase of bipolar disorder. Compounds can be evaluated for utility in treating these conditions by determining whether they are capable of blocking neuronal M-channels.

Blockade of neuronal m-channels as a therapeutic approach to the

Compounds of Formula I have been shown to enhance the release of the neurotransmitter acetylcholine, and thus may be useful in the treatment of diseases of man, such as in Alzheimer's disease and other conditions involving learning and cognition, where subnormal levels of this neurochemical are found. The compounds of this invention can be described as shown in Formula I ##STR1## where Q is ##STR2## R.sup.1 is 4-, 3-, or 2-pyridyl, pyrimidyl, pyrazinyl, or fluoro-4-pyridyl;

Disubstituted polycyclic systems as cognition enhancers

Compounds of Formula I have been shown to enhance the release of the neurotransmitter acetylcholine, and thus may be useful in the treatment of diseases of man, such as in Alzheimer's disease and other conditions involving learning and cognition, where subnormal levels of this neurochemical are found. The compounds of this invention can be described as shown in Formula I ##STR1## where Q is ##STR2## R.sup.1 is 4-,3-, or 2-pyridyl, pyrimidyl, pyrazinyl, or fluoro-4-pyridyl; R.sup.2 and R.sup.3 are independently H, F, Cl, Br, NO.sub.2, OH, --R.sup.4, --O--R.sup.4, --CO.sub.2 R.sup.4, --COR.sup.4, --CONH.sub.2, --CONHR.sup.4, --CONR.sup.4 R.sup.4', --S(O).sub.m2 -- R.sup.4, NH.sub.2, CF.sub.3, NHR.sup.4, NR.sup.4 R.sup.4' ;

Compounds of Formula I have been shown to enhance the release of the neurotransmitter acetylcholine and thus may be useful in the treatment of diseases learning and cognition. The compounds of this invention are ##STR1## where Q is ##STR2## A and B are independently selected from H, R.sup.4, --OH and --OCOR.sup.4, or

Neurotransmitter releasers useful for cognition enhancement

This invention relates to the preparation of cyclic urea compounds. More specifically, this invention is directed to methods for selectively alkylating diamines, methods for selectively converting a mixture of alkylated and non-alkylated diamines to cyclic urea compounds, methods to purify cyclic urea compounds having a single N-substitution, methods to convert a cyclic urea compound having a single N-substitution to a cyclic urea compound having either symmetrical or non-symmetrical N,N'-disubstitution, and methods to remove protecting groups from cyclic urea compounds.

Preparation of cyclic urea compounds

Compounds of the following formula have been shown to enhance the release of the neurotransmitter acetylcholine, and thus may be useful in the treatment of diseases of man involving learning and cognition, where subnormal levels of this neurochemical are found ##STR1## wherein R.sup.1 is 4-,3-, or 2-pyridyl, 2-fluoro-4-pyridyl or 3-fluoro-4-pyridyl;

This invention relates to monoamine oxidase-B (MAO-B) inhibitory 5-substituted 2,4-thiazolidinediones, such as Formula I, to pharmaceutical compositions thereof, process of preparation, and methods of use in mammals to treat cognitive disorders, neurological dysfunction, and/or mood disturbances such as, but not limited to degenerative nervous system diseases. ##STR1##

Monoamine oxidase-B (MAO-B) inhibitory 5-substituted

Compounds of Formula I have been shown to enhance the release of the neurotransmitters acetylcholine, dopamine and serotonin; and thus may be useful in the treatment of diseases of man where subnormal levels of this neurochemical are found such as in Alzheimer's disease and other conditions involving learning and cognition; and Parkinson's disease. The compounds of this invention can be described as shown in Formula I ##STR1## where A is a heteroaromatic system.

3,3'-disubstituted-1,3-dihydro-2H-pyrrolo[2,3-b]heterocyclic-2-one

The invention relates to benylalcohol phospholipase A.sub.2 inhibitors, pharmaceutical compositions containing them, and methods of treating phospholipase A.sub.2 -mediated conditions in mammals by administration of a therapeutically effective amount of such a benzylalcohol phospholipase A.sub.2 inhibitor.

Benzylalcohol phospholipase A.sub.2 inhibitors

The invention relates to benzylketone phospholipase A.sub.2 inhibitors, pharmaceutical compositions containing them, and methods of treating phospholipase A.sub.2 -mediated conditions in mammals by administration of a therapeutically effective amount of such a benzylketone phospholipase A.sub.2 inhibitor. These compounds are also intermediates in the synthesis of other PLA.sub.2 inhibitors.

Benzylketone phospholipase A.sub.2 inhibitors

The invention relates to benzylamine phosphilipase A.sub.2 inhibitors, pharmaceutical compositions containing them, and methods of treating phospholipase A.sub.2 -mediated conditions in mammals by administration of a therapeutically effective amount of such a benzylamine phospholipase A.sub.2 inhibitor.

Antiinflammatory PLA.sub.2 inhibitors

Antihypercholesterolemic thioimidazoles of the formula ##STR1## or a pharmaceutical acceptable salt thereof, wherein R.sup.1 and R.sup.2 independently are H, F, Cl, CF.sub.3, alkyl of 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms;

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New Castle, DE, United States of America

Wendell W Wilkerson