Abstract: Disclosed are compounds of the formula: ##STR1## or pharmaceutically acceptable salts thereof; wherein n is zero or 1; R.sup.4, R.sup.5, R.sup.6 are independently hydrogen, nitro, amino, halo, haloalkyl, cyano, alkyl, cycloalkyl, alkenyl, alkynyl, azido, acylamino, alkylsulfonyl, aryl, substituted aryl, heteroaryl, alkoxy, trialkylsilyl-substituted alkoxy, aryloxy, substituted aryloxy, heteroaryloxy, a heterocyclic group, a heterocyclicoxy group, aralkoxy, or haloalkoxy; and R.sup.c and R.sup.d are defined in the specification. These compounds have high binding to the glycine site of the NMDA receptor. Also disclosed are methods of treating pathophysiologic conditions associated with neuronal degeneration, convulsions, anxiety, chronic pain, pyschosis, opiate tolerance, and inducing anesthesia.

Abstract: Methods for coating substrates are described. The methods comprise coating at least a portion of a substrate with particular coating materials. The coating materials can be crosslinked and coated onto a substrate. Alternatively, the coating materials may be covalently bonded to the substrates. The coating materials might themselves functionalize the substrate, or provide a biocompatible coating on the substrate. The coating materials might also include electrophilic or nucleophilic groups that allow for the subsequent reaction of the coating materials with additional reagents. The present invention also provides coated workpieces, particularly medical workpieces having a surface for contacting tissue or blood. These workpieces comprise a first layer and a second layer. The first layer comprises a molecular tether covalently bonded to the surface.

Abstract: Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Down's syndrome, treating or preventing adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, inducing anesthesia, and treating or preventing opiate tolerance are disclosed by administering to an animal in need of such treatment or prevention a substituted or unsubstituted pyridine and pyridine (N-oxide) analogs of 4-hydroxydihydroquinolones, tetrahydroquinoline-trione-oximes and quinoxalones, tautomers and pharmaceutically acceptable salts thereof, which have high binding to the glycine receptor.

Abstract: Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders.

Abstract: Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders.

Abstract: Disclosed are methods of preparing azepines by a multistep synthesis including a Diels-Alder reaction. Also disclosed are methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, inducing anesthesia and treating or preventing opiate tolerance are disclosed by administering to an animal in need of such treatment an azepine which has high binding to the NMDA glycine site.

Abstract: The invention relates to 5-(iminomethano)-10,11-dihydro-5H-dibenzo?a,d!cycloheptene and derivatives thereof. The invention also relates to the use of such compounds for the treatment or prevention of neuronal loss in ischemia, hypoxia, brain or spinal chord trauma, as well as for the treatment of Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome.

Abstract: Disclosed herein are substituted or unsubstituted 1,2,3,4-tetrahydroquinoline-2,3,4-trione-3 or 4-oximes or pharmaceutically acceptable salts thereof that have high binding to the glycine receptor and are usefully administered to animals for the treatment or prevention of the adverse consequences of the hyperactivity of the excitatory amino acids, or neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, for the treatment of anxiety, chronic pain, convulsions, and neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome; and for the inducement of anesthesia.

Abstract: Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders.

Abstract: Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, and inducing anesthesia are disclosed by administering to an animal in need of such treatment an alkyl or azido-substituted 1,4-dihydroquinoxaline-2,3-dione or pharmaceutically acceptable salts thereof, which have high binding to the glycine receptor.

Abstract: Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, inducing anesthesia and treating psychosis are disclosed by administering to an animal in need of such treatment a compound having high affinity for the glycine binding site, lacking PCP side effects and which crosses the blood brain barrier of the animal.Also disclosed are novel 1,4-dihydroquinoxaline-2,3-diones, and pharmaceutical compositions thereof. Also disclosed are highly soluble ammonium salts of 1,4-dihydroquinoxaline-2,3-diones.

Abstract: Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions and inducing anesthesia are disclosed by administering to an animal in need of such treatment a substituted or unsubstituted 4-hydroxy-3-nitro-1,2-dihydroquinolin-2-one or pharmaceutically acceptable salts thereof which have high binding to the glycine receptor.

Abstract: Disclosed is a method of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma or hypoglycemia. The method comprises administering to an animal a compound of the formula: ##STR1## or a pharmaceutically acceptable salt thereof; wherein n is zero or 1; R.sup.4, R.sup.5, R.sup.6 are independently hydrogen, nitro, amino, halo, haloalkyl, cyano, alkyl, cycloalkyl, alkenyl, alkynyl, azido, acylamino, alkylsulfonyl, aryl, substituted aryl, heteroaryl, alkoxy, trialkylsilyl-substituted alkoxy, aryloxy, substituted aryloxy, heteroaryloxy, a heterocyclic group, a heterocyclicoxy group, aralkoxy, or haloalkoxy; and R.sup.c and R.sup.d are defined in the specification. These compounds have high binding to the glycine site of the NMDA receptor.

Abstract: Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, inducing anesthesia and treating psychosis are disclosed by administering to an animal in need of such treatment a compound having high affinity for the glycine binding site, lacking PCP side effects and which crosses the blood brain barrier of the animal.Also disclosed are novel 1,4-dihydroquinoxaline-2,3-diones, and pharmaceutical compositions thereof. Also disclosed are highly soluble ammonium salts of 1,4-dihydroquinoxaline-2,3-diones.

Abstract: N,N-disubstituted-guanidines, e.g., of the formula ##STR1## wherein R and R' are substituted or unsubstituted hydrocarbon groups. Methods are provided for the treatment of psychosis and hypertension by administering an effective amount of an N,N'-disubstituted guanidine which, preferably, has a high affinity for the sigma receptor.

Abstract: Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions and inducing anesthesia are disclosed by administering to an animal in need of such treatment a compound which has high binding to the glycine receptor.

Abstract: A molecularly imprinted substrate and sensors employing the imprinted substrate for detecting the presence or absence of analytes are described. One embodiment of the invention comprises first forming a solution comprising a solvent and (a) a polymeric material capable of undergoing an addition reaction with a nitrene, (b) a crosslinking agent (c) a functionalizing monomer and (d) an imprinting molecule. A silicon wafer is spincoated with the solution. The solvent is evaporated to form a film on the silicon wafer. The film is exposed to an energy source to crosslink the substrate, and the imprinting molecule is then extracted from the film. The invention can be used to detect an analyte by forming films which are then exposed to a reaction energy to form a crosslinked substrate. The imprinting molecules are extracted from the crosslinked substrate. The film is exposed to one or more of the imprinting molecules for a period of time sufficient to couple the imprinting molecules to the film.

Abstract: Methods for covalently modifying surfaces of various substrates are disclosed, along with various substrates having surfaces modified by such methods. Candidate surfaces include various polymeric, siliceous, metallic, allotrophic forms of carbon, and semiconductor surfaces. The surfaces are exposed to a reagent, having molecules each comprising a nitrenogenic group and a functionalizing group, in the presence of energized charged particles such as electrons and ions, photons, or heat, which transform the nitrenogenic reagent to a nitrene intermediate. The nitrene covalently reacts with any of various chemical groups present on the substrate surface, thereby effecting nitrene addition of the functionalizing groups to the substrate surface. The functionalizing groups can then participate in downstream chemistry whereby any of a large variety of functional groups, including biological molecules, can be covalently bonded to the surface, thereby dramatically altering the chemical behavior of the surface.

Abstract: Methods for covalently modifying surfaces of various substrates are disclosed, along with various substrates having surfaces modified by such methods. Candidate surfaces include various polymeric, siliceous, metallic, allotrophic forms of carbon, and semiconductor surfaces. The surfaces are exposed to a reagent, having molecules each comprising a nitrenogenic group and a functionalizing group, in the presence of energized charged particles such as electrons and ions, photons, or heat, which transform the nitrenogenic reagent to a nitrene intermediate. The nitrene covalently reacts with any of various chemical groups present on the substrate surface, thereby effecting nitrene addition of the functionalizing groups to the substrate surface. The functionalizing groups can then participate in downstream chemistry whereby any of a large variety of functional groups, including biological molecules, can be covalently bonded to the surface, thereby dramatically altering the chemical behavior of the surface.

Abstract: The invention relates to a method for the treatment or prophylaxis of psychosis, depression, hypertension, or anxiety in an animal by administering an effective amount of an N,N'-disubstituted guanidine or 2-iminoimadazolidine having an affinity for the sigma receptor. The invention also relates to the novel guanidines of the invention as well as pharmaceutical compositions thereof.