Abstract: A process is disclosed for the production of polyphenol oligomers having n polyphenol monomeric units, n being an integer from 2-18. The process includes coupling of a protected polyphenol, having protected phenolic hydroxyl groups, with a C-4 functionalized polyphenol monomer. The protected polyphenol may be a protected polyphenol monomer or a protected polyphenol oligomer having 2-17 monomeric units. Advantageously, polyphenol monomeric units forming the polyphenol oligomers may be the same or different flavanoid compounds.

Abstract: Various processes are disclosed for preparing procyanidin oligomers having (4,8)-interflavan linkages. In an improved process, a tetra-O-protected-epicatechin or -catechin monomer or oligomer is coupled with a protected, C-4 alkoxy-activated-epicatechin or -catechin monomer in the presence of an acidic clay instead of a Lewis acid. In a second process, a 5,7,3?,4?-tetra-O-protected or preferably penta-O-protected-epicatechin or -catechin monomer or oligomer is reacted with a tetra-O-protected or preferably penta-O-protected-epicatechin or -catechin monomer having a thio activating group at the C-4 position; the coupling is carried out in the presence of silver tetrafluoroborate. In third process, two molecules of a penta-O-protected-epicatechin or -catechin monomer activated with a 2-(benzothiazolyl)thio group at the C-4 position are self-condensed in the presence of silver tetrafluoroborate.

Abstract: The present invention provides 4-substituted-2-azetidinone compounds, bicyclic 2-5-diketopiperazine compounds, and pharmaceutical compositions thereof that are potent, safe and effective neuroprotective agents. Due to their strong central nervous system (CNS) activity, the compounds can be used to enhance memory and to treat a variety of neurological disorders. The compounds are particularly useful for treating neurological disorders caused by, or associated with, CNS trauma.

Abstract: The present invention relates to the preparation and biological activity of 3-deoxy-Dmyo-inositol ether lipid analogs as inhibitors of phosphatidylinositol-3-kinase signaling and cancer cell growth. The compounds of the present invention are useful as anti-tumor 5 agents which effectively inhibit the growth of mammalian cells.

Abstract: Oligomeric procyanidins containing 4?-linked epicatechin units are rare in nature and have hitherto not been accessible through stereoselective synthesis. Provided herein is the preparation of the prototypical dimer, epicatechin-4?,8-epicatechin, by reaction of the protected 4-ketones with aryllithium reagents derived by halogen/metal exchange from the aryl bromides. Removal of the 4-hydroxyl group from the resulting tertiary benzylic alcohols is effected by tri-n-butyltin hydride and trifluoroacetic acid in a completely stereoselective manner, resulting in hydride delivery exclusively from the ? face.

Abstract: Various processes are disclosed for preparing protected epicatechin oligomers having (4?,8)-interflavan linkages. In one process, a tetra-O-protected epicatechin monomer or oligomer is coupled with a protected, C-4 activated epicatechin monomer in the presence of an acidic clay such as a mortmorillonite clay. In another process, a 5,7,3?,4?-benzyl protected or a 3-acetyl-, 5,7,3?,4?-benzyl protected epicatechin or catechin monomer or oligomer is reacted with 3-O-acetyl-4-[(2-benzothiazolyl)thio]-5,7,3?,4?-tetra-O-benzylepicatechin in the presence of silver tetrafluoroborate. In another process, two 5,7,3?,4?-benzyl protected epicatechin monomers activated with 2-(benzothiazolyl)thio groups at the C-4 positions are cross-coupled in the presence of silver tetrofluoroborate. A process is also disclosed for reacting an unprotected epicatechin or catechin monomer with 4-(benzylthio)epicatechin or catechin.

Abstract: The present invention provides compounds, specifically novel tropane analogs, capable of acting as inhibitors of reuptake of monoamines. In preferred embodiments, these compositions are selective inhibitors of serotonin and/or norepinephrine reuptake. Also provided herein are pharmaceutical compositions comprising novel tropane analogs and a pharmaceutically acceptable carrier, and methods for treating conditions in which inhibition of reuptake of monoamines is desired. The inventive compositions as described herein are also useful for medical therapy and diagnosis.

Abstract: A process is disclosed for the production of polyphenol oligomers having n polyphenol monomeric units, n being an integer from 2-18. The process includes coupling of a protected polyphenol, having protected phenolic hydroxyl groups, with a C-4 functionalized polyphenol monomer. The protected polyphenol may be a protected polyphenol monomer or a protected polyphenol oligomer having 2-17 monomeric units. Advantageously, polyphenol monomeric units forming the polyphenol oligomers may be the same or different flavanoid compounds.

Abstract: The present invention provides bicyclic metabotropic glutamate receptor ligands, as well as compositions comprising such ligands, and methods for their use.

Abstract: A process is disclosed for the production of polyphenol oligomers having n polyphenol monomeric units, n being an integer from 2-18. The process includes coupling of a protected polyphenol, having protected phenolic hydroxyl groups, with a C-4 functionalized polyphenol monomer. The protected polyphenol may be a protected polyphenol monomer or a protected polyphenol oligomer having 2-17 monomeric units. Advantageously, polyphenol monomeric units forming the polyphenol oligomers may be the same or different flavanoid compounds.

Abstract: The invention provides a compound of formula (I): wherein R1, R2, R3, and Y have any of the meanings defined in the specification; as well a pharmaceutical composition comprising a compound of formula I; intermediates and methods useful for preparing a compound of formula I; and therapeutic methods for treating drug addiction, Parkinson's disease or depression comprising administering a compound of formula I, to a mammal in need of such treatment.

Abstract: The present invention relates to the preparation and biological activity of 3-deoxy-Dmyo-inositol ether lipid analogs as inhibitors of phosphatidylinositol-3-kinase signaling and cancer cell growth. The compounds of the present invention are useful as anti-tumor 5 agents which effectively inhibit the growth of mammalian cells.

Abstract: Various processes are disclosed for preparing protected epicatechin oligomers having (4&bgr;,8)-interflavan linkages. In one process, a tetra-O-protected epicatechin monomer or oligomer is coupled with a protected, C-4 activated epicatechin monomer in the presence of an acidic clay such as a mortmorillonite clay. In another process, a 5,7,3′,4′-benzyl protected or a 3-acetyl-, 5,7,3′,4′-benzyl protected epicatechin or catechin monomer or oligomer is reacted with 3-O-acetyl-4-[(2-benzothiazolyl)thio]-5,7,3′,4′-tetra-O-benzylepicatechin in the presence of silver tetrafluoroborate. In another process, two 5,7,3′,4′-benzyl protected epicatechin monomers activated with 2-(benzothiazolyl)thio groups at the C-4 positions are cross-coupled in the presence of silver tetrofluoroborate. A process is also disclosed for reacting an unprotected epicatechin or catechin monomer with 4-(benzylthio) epicatechin or catechin.

Abstract: Oligomeric procyanidins containing 4&agr;-linked epicatechin units are rare in nature and have hitherto not been accessible through stereoselective synthesis. Provided herein is the preparation of the prototypical dimer, epicatechin-4&agr;,8-epicatechin, by reaction of the protected 4-ketones with aryllithium reagents derived by halogen/metal exchange from the aryl bromides. Removal of the 4-hydroxyl group from the resulting tertiary benzylic alcohols is effected by tri-n-butyltin hydride and trifluoroacetic acid in a completely stereoselective manner, resulting in hydride delivery exclusively from the &bgr; face.

Abstract: The present invention relates to compounds particularly asymmetric urea compounds which are labeled with one or more radioisotopes and which are suitable for imaging or therapeutic treatment of tissues, organs, or tumors which express NAALADase and/or PSMA. In another embodiment, the invention relates to methods of imaging tissues, organs, or tumors using radiolabeled compounds of the invention, particularly tissues, organs, or tumors which express NAALADase and/or PSMA to which the compounds of the invention have an affinity.

Abstract: The invention concerns compounds of formula CH3—R1—(CH2)2—R2 wherein: R1 is selected among a tertiary alcohol; a 1,2-diol; a halohydrine; an epoxide; an alkene; an aldehyde or an &agr;-hydroxyaldehyde; and R2 is selected among a methylenediphosphonate; a difluoromethylenediphosphonate; or a monofluoromethylenediphosphonate. The invention also concerns the uses of said compounds as selective inhibitors of T&ggr;9&dgr;2 lymphocytes, and their uses, in particular for therapeutic purposes.

Abstract: The present invention relates to novel compounds and formulations thereof which compounds are ligands, e.g., agonists or antagonists, for a metabotropic glutamate receptor or a NAALADase enzyme or both. The present invention also relates to methods of modulating the activity of a metabotropic glutamate receptor or a NAALADase enzyme or both, e.g., in a subject in need thereof, using a compound or formulation of the present invention. The present invention also relates to methods of treating a subject suffering from a chronic or acute disease, malady or condition due at least in part to an abnormality in the activity of an endogenous metabotropic glutamate receptor or a NAALADase enzyme or both, using a compound or formulation of the present invention.

Abstract: The present invention relates to the preparation and biological activity of 3-deoxy-Dmyo-inositol ether lipid analogs as inhibitors of phosphatidylinositol-3-kinase signaling and cancer cell growth. The compounds of the present invention are useful as anti-tumor 5 agents which effectively inhibit the growth of mammalian cells.

Abstract: The invention concerns compounds CH3—R1—(CH1)2—R2 wherein: R1 is selected among a tertiary alcohol; a 1,2-diol; a halohydrine; an apoxide; an alkene; an aldehyde or an &agr;-hydroxyaldehyde; and R2 is selected among a methylenediphosphonate; a difluoromethylenediphosphonate; or a monofluoromethylenediphosphoneate. The invention also concerns the uses of said compounds as selective inhibitors of T&ggr;9&dgr;2 lymphocytes, and their uses, in particular for therapeutic purposes.

Abstract: A process is disclosed for the production of polyphenol oligomers having n polyphenol monomeric units, n being an integer from 2-18. The process includes coupling of a protected polyphenol, having protected phenolic hydroxyl groups, with a C-4 functionalized polyphenol monomer. The protected polyphenol may be a protected polyphenol monomer or a protected polyphenol oligomer having 2-17 monomeric units. Advantageously, polyphenol monomeric units forming the polyphenol oligomers may be the same or different flavanoid compounds.