Abstract: Disclosed herein are substituted cyclohexanone-based NMDA receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: By disrupting a natural process used by developing mammalian brains to prune and delete surplus neurons, surgical anesthetics and other drugs that suppress brain activity in fetuses and infants can trigger permanent pathological brain damage. That type of damage can be prevented by drug interventions that block one or more “upstream” events that otherwise would lead to the release of “Cytochrome C”, a messenger molecule that triggers apoptosis (programmed cell death) among immature neurons. Lithium is a potent protective agent that can be coadministered along with ketamine or other NMDA-acting or GABA-acting anesthetics and anticonvulsants. Xenon gas triggers only mild damage, and can enable improved anesthesia when combined with other drugs. Other protective drugs (also called safener drugs), and treatments that can prevent or minimize fetal alcohol syndrome, also are disclosed.

Abstract: Disclosed herein are compounds of Formula (I), (II), and (III) pharmaceutical compositions comprising the same, methods of modulating the activity a thrombopoietin receptor using the same, methods of identifying compounds as thrombopoietin receptor modulators, and methods of treating disease by administering a compound of the invention to a patient in need thereof.

Abstract: Administration of 1,3-dimethoxymethyl-5,5-diphenylbarbituric acid and its related compounds with food increases the bioavailability of these compounds. The ratios (fasting/fed) for geometric mean AUC0-t were 35.6% (DMMDPB), 36.6% (MMMDPB) and 65.3% (DPB) and the geometric mean Cmax were 14.6% (DMMDPB), 31.9% (MMMDPB) and 62.9% (DPB). The cyclic ureides may be administered to a subject before or after ingestion of food within a defined time period.

Abstract: A pharmaceutical composition comprises a pharmaceutically effective amount of an active ingredient and low crystallinity cellulose having a crystallinity index of less than about 75% as measured by X-ray diffraction. The compositions advantageously may be provided in tablet form or granulate form and provide good stability against moisture degradation.

Abstract: The present invention relates to compounds of formula (I): useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Abstract: The present invention relates to compounds of formula (I): useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Abstract: The invention provides novel scoring patterns for a wide variety of tablets that contain specific drugs or contain drugs in certain drug classes, and methods of treatment with layered tablets and fractional tablets derived from breaking said tablets.

Abstract: This invention relates to a chemical compound that inhibits the apoptotic activity of the protease Omi/HtrA2 and homologous proteins. This protease Omi/HtrA2 is present in all mammalian cells so that inhibition of apoptosis in this fashion results enhanced cellular health and therapeutic effects.

Abstract: A method of treating movement disorders comprises administering to a human or animal subject in need of treatment a therapeutically effective amount of at least one compound according to the following formula: wherein R3 and R4 are each independently selected from the group consisting of lower alkyl, phenyl and lower alkyl substituted phenyl, and R1 and R2 are each independently either a hydrogen atom or a radical of the formula wherein R5 and R6 are each independently selected from the group consisting of H, lower alkyl, phenyl and lower alkyl substituted phenyl, its pharmaceutically acceptable salts, prodrugs, and metabolites thereof.

Abstract: The present invention relates to triaryl-oxy-aryloxy-pyrimidine-2,4,6-trione; metalloproteinase inhibitors of the formula wherein X, A, Y, B, G, W, and R1 are as defined in the specification, and to pharmaceutical compositions and methods of treating inflammation, cancer and other disorders.

Abstract: The subject invention concerns novel compounds that are useful as ultrashort acting hypnotic barbiturates. Specifically exemplified are derivatives of barbituric and thiobarbituric acids. They are rapidly metabolized by blood and tissue enzymes to form polar metabolites with no hypnotic activity and which are rapidly eliminated.

Abstract: The present invention relates to novel non-sedating barbituric acid derivatives, pharmaceutical compositions containing them and methods of neuroprotection in cases of cerebral ischemia, head trauma and other acute neurologic injuries, and prevention of resulting neuronal damage. The invention also relates to the use of non-sedating barbituric acid derivatives given in a manner and dosage effective to produce blood levels and brain levels of these drugs and/or their active metabolites sufficient to provide a therapeutic effect.

Abstract: The present application describes novel barbituric acid derivatives of formula I: or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, B, L, R1, W, Z, Ua, Xa, Ya, and Za are defined in the present specification, which are useful as TNF-? converting enzyme (TACE) and matrix metalloproteinases (MMP) inhibitors.

Abstract: The present invention relates to N-substituted-heteroaryloxy-aryloxy-2,4,6-trione metalloproteinase inhibitors of the formula wherein X, A, Y, B, G, and R1 are as defined in the specification, and to pharmaceutical compositions and methods of treating inflammation, cancer and other disorders.

Abstract: A method of N-alkoxyalkylating ureides according to the invention comprises reacting a ureide of structure I: with an alkylating agent of structure III: in the presence of a basic catalyst in an aprotic reaction medium. The ureide may be a 5,5-disubstituted barbituric acid, or it may be phenytoin, glutethimide, and ethosuximide. The alkylating agent is an ester of a sulfonic acid. The base may be a hydride or amine. A preferred process comprises N-alkoxyalkylating 5,5-diphenyl-barbituric acid with methoxymethyl methanesulfonate in the presence of di-isopropyl ethyl amine and isolating the resultant N,N?-bismethoxymethyl-5,5-diphenyl-barbituric acid. The invention also contemplates the novel compounds N-methoxymethyl-5,5-diphenylbarbituric acid, N-methoxymethyl ethosuximide, and N-methoxymethyl glutethimide, and a method comprising administering them to a patient.

Abstract: Non-peptide GnRH agents that inhibit the effect of gonadotropin-releasing hormone are described. Such agents are useful for treating mammalian reproductive disorders and steroid hormone-dependent tumors as well as for regulating fertility, where suppression of gonadotropin release is indicated.

Abstract: A method for minimizing scarring and preventing excessive scar formation at an injury site is disclosed. The method involves the topical and/or local application of a therapeutically effective amount of a defibrinogenating agent or of a fibrinolytic agent that may be delivered in an appropriate vehicle in a controlled- or timed-release manner. In accordance with the principles of the invention, the defibrinogenating agent or fibrinolytic agent is applied as a coating on, or is irradiated or impregnated into or onto a delivery vehicle such as, for example, sutures, dissolvable sutures, bandages, gauze pads, or other types of first aid bandaging materials. Such application may take the form of a controlled- or timed-release aspect of either the vehicle, the delivery material or the therapeutic agent, such that the release of the therapeutic agent may be regulated to produce an appropriate therapeutic pattern or defibrinogenation or fibrinolysis.

Abstract: The invention relates to a pharmaceutical composition comprising a compound of the formula (I): 1

Abstract: A method of treating movement disorders comprises administering to a human or animal subject in need of treatment a therapeutically effective amount of at least one compound according to the following formula: 1

Abstract: The present invention relates to the discovery of a novel class of compounds that inhibit the replication of human immunodeficiency virus (HIV) and approaches to identify these compounds. More specifically, it has been found that enzymatically prepared alpha-hydroxyglycinamide and synthetically prepared alpha-hydroxyglycinamide inhibit the replication of HIV in human serum. Embodiments include methods to identify modified glycinamide compounds that inhibit HIV, methods to isolate and synthesize modified glycinamide compounds, and therapeutic compositions comprising these compounds.

Abstract: Neonatal mice with classic inherited retinal degeneration (Pdebrd1/Pdebrd1) are disclosed which fail to mount reactive retinal neovascularization in a mouse model of oxygen-induced proliferative retinopathy. Also disclosed is a comparable human paradigm: spontaneous regression of retinal neovascularization associated with long-standing diabetes mellitus which occurs when retinitis pigmentosa becomes clinically evident. Both mouse and human data indicate that reactive retinal neovascularization either fails to develop or regresses when the number of photoreceptor cells is markedly reduced. The results show that a functional mechanism underlying this anti-angiogenic state is failure of the predicted up-regulation of vascular endothelial growth factor (VEGF), although other growth factors may also be involved. Preventive and therapeutic methods useful against both proliferative and degenerative retinopathies are also disclosed.

Abstract: The invention is directed to methods and compositions for inhibiting caspase-independent apoptosis. In particular, methods and compositions for inhibiting Omi/HtrA2 activity, as well as method for identifying other inhibitors of Omi/HtrA2. Also disclosed are Omi/HtrA2 specific substrates and methods for identifying other substrates of Omi/HtrA2.

Abstract: The subject invention concerns novel compounds that are useful as ultrashort acting hypnotic barbiturates. Specifically exemplified are derivatives of barbituric and thiobarbituric acids. They are rapidly metabolized by blood and tissue enzymes to form polar metabolites with no hypnotic activity and which are rapidly eliminated.

Abstract: An antibacterial composition is provided which comprises a base, an antibacterial agent consisting of a silver-supporting inorganic compound and a water-soluble salt of a nitrogen atom-containing 6-membered heterocyclic compound. In the antibacterial composition, the silver component susceptible to discoloration is effectively stabilized by the use of the water-soluble salt of a nitrogen atom-containing 6-membered heterocyclic compound and therefore, the antibacterial composition never or hardly undergoes any discoloration with the lapse of time.

Abstract: Methods of providing neuroprotection are disclosed comprising administering a non-sedative barbiturate compound in an amount sufficient to achieve neuroprotection in a mammalian subject. Preferred compounds are in the family of diphenylbarbituric acid and analogs.

Abstract: Disclosed herein are compounds of Formula I, 1

Abstract: The invention relates to the use of pharmaceutical compositions comprising GABA-receptor modulators in ophthalmology, for the prevention and/or treatment of neurodegenerative diseases of the eye, whereby the GABA-receptor modulators are selected from the group comprising benzodiazepines, benzodiazepine-receptor ligands of various structures, beta-carbolines, barbiturates, barbituric acid derivatives and/or neurosteriods.

Abstract: The present invention pertains to derivatives of 5,5-disubstituted pyrimidine-2,4,6,-trianones having the formula: wherein R1, R2, R3, and R4 are described herein. These compounds have antitumor and antimetastatic activity.

Abstract: This invention provides compounds defined by Formula I

Abstract: Buccal aerosol sprays or capsule using polar and non-polar solvent have now been developed which provide biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprises formulation I: polar solvent 37-98.58%, active compound 0.005-55%, optionally containing flavoring agent 0.1-10%.

Abstract: One aspect of the present invention relates to compositions and methods for discouraging improper use of habit-forming and addictive drugs, such as oxycodone. In a preferred embodiment, a habit-forming or addictive drug is chemically modified to block its physiological activity until the drug is transformed to a physiologically active form in the mammalian gastrointestinal tract.

Abstract: The present invention relates to pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula wherein X, Y, A, B and R1 are as defined in the specification, and to pharmaceutical compositions and methods of treating inflammation, cancer and other disorders.

Abstract: Compound having the formula (I), 1

Abstract: Methods are disclosed for improving age-related decreases in cortical function by increasing the activity of inhibitory pathways, such as GABA-ergic pathways, in the central nervous system. In particular examples, subjects with age-related decreases in cortical function are treated by administering therapeutically effective amounts of a GABA-ergic agonist. The disclosed methods also enable screening for drugs that inhibit an age-related decline in cortical function, for example by exposing a subject to a test agent, and measuring an increase in GABA-ergic cortical inhibitory activity.

Abstract: The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.

Abstract: The subject invention concerns novel compounds that are useful as ultrashort acting hypnotic barbiturates. Specifically exemplified are derivatives of barbituric and thiobarbituric acids. They are rapidly metabolized by blood and tissue enzymes to form polar metabolites with no hypnotic activity and which are rapidly eliminated.

Abstract: The present invention relates to triaryl-oxy-aryloxy-pyrimidine-2,4,6-trione; metalloproteinase inhibitors of the formula 1

Abstract: Method of producing thiobarbituric acid derivatives of formula I wherein R1 is SH, S−M+ or CH3S—, and M+ is an alkali metal ion, by hydrogenolysis of a compound of formula II wherein R2 is chlorine or CH3O—, with a) a hydrogenolysis agent in the presence of an inert solvent and by a direct reaction of the hydrogenolysis product with an alkali metal methylate in methanol, or b) with a hydrogenolysis agent in the presence of an inert solvent and in the presence of a methylation reagent, and subsequently with an alkali metal methylate in methanol, as well as the use of these compound of formula I in the production of 7-[(4,6-dimethoxy-pyrimidin-2-yl)thio]-3-methylphthalide.

Abstract: The present invention relates to N-substituted-heteroaryloxy-aryloxy-2,4,6-trione metalloproteinase inhibitors of the formula 1

Abstract: A method of N-alkoxyalkylating ureides according to the invention comprises reacting a ureide of structure I: with an alkylating agent of structure III: in the presence of a basic catalyst in aprotic reaction medium. The ureide may be a 5,5-disubstituted barbituric acid, or it may be phenytoin, glutethimide, and ethosuximide. The alkylating agent is an ester of a sulfonic acid. The base may be a hydride or amine. A preferred process comprises N-alkoxyalkylating 5,5-diphenyl-barbituric acid with methoxymethyl methanesulfonate in the presence of di-isopropyl ethyl amine and isolating the resultant N,N′-bismethoxymethyl-5,5-diphenyl-barbituric acid. The invention also contemplates the novel compounds N-methoxymethyl-5,5-diphenylbrbituric acid, N-methoxymethyl ethosuximide, and N-methoxymethyl glutethimide, and a method comprising administering them to a patient.

Abstract: This invention pertains to active barbituric acid analogs which inhibit HIF-1 activity (e.g., the interaction between HIF-1&agr; and p300) and thereby inhibit angiogenesis, tumorigensis, and proliferative conditions, such as cancer. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HIF-1 activity, and to inhibit angiogensis, tumorigensis, and proliferative conditions, such as cancer.

Abstract: The present invention relates to the treatment of depression and/or anxiety by the administration of a combination of a specific class of NK-1 receptor antagonists and an antidepressant or anti-anxiety agent.

Abstract: Buccal aerosol sprays or capsule using polar and non-polar solvent have now been developed which provide biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprises formulation I: aqueous polar solvent 30-99.89%, active compound 0.001-60%, optionally containing flavoring agent 0.1-10%. Propellant 2-10%. The non polar composition of the invention comprises formulation II: non-polar solvent 20-85%, active compound 0.005-50%, and optionally flavoring agent 0.1-10% and propellant 50-80%.

Abstract: Novel “bispolyamine” inhibitor compounds of polyamine transport are disclosed. These compounds are useful pharmaceutical agents for treating diseases where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. These compounds display desirable activities both for diagnostic and research assays and therapy.

Abstract: The present invention provides a method of treating a visceral pain syndromes in a mammal. The method includes administering to the mammal an effective amount of a selective norepinephrine (NE)-serotonin (5-HT) reuptake inhibitor (NSRI), e.g., milnacipran.

Abstract: The present invention relates to therapeutically active novel amino, carboxy, alkyl derivatives of barbituric acid of Formula (I), wherein at least one of R1, R2, R3 or R4 comprises an NH2 moiety and at least one of R1, R2, R3 or R4 comprises one COOH moiety. Also provided is a method of preparing compounds of formula (I), and pharmaceutical compositions comprising the compounds. The novel compounds act as modulators of metabotropic glutamate receptors and, as such, are useful in treating diseases of the central nervous system related to the metabotropic glutamate receptor system.

Abstract: The present invention relates to novel non-sedating barbituric acid derivatives, pharmaceutical compositions containing them and methods of neuroprotection in cases of cerebral ischemia, head trauma and other acute neurologic injuries, and prevention of resulting neuronal damage. The invention also relates to the use of non-sedating barbituric acid derivatives given in a manner and dosage effective to produce blood levels and brain levels of these drugs and/or their active metabolites sufficient to provide a therapeutic effect.

Abstract: Methods of providing neuroprotection are disclosed comprising administering a non-sedative barbiturate compound in an amount sufficient to achieve neuroprotection in a mammalian subject. Preferred compounds are in the family of diphenylbarbituric acid and analogs.

Abstract: A method of N-alkoxyalkylating ureides according to the invention comprises reacting a ureide of structure I with an alkylating agent of structure III in the presence of a basic catalyst in an aprotic reaction medium. The ureide may be a 5,5-disubstituted barbituric acid, or it may be phenytoin, glutethimide, and ethosuximide. The alkylating agent is an ester of a sulfonic acid. The base may be a hydride or amine. A preferred process comprises N-alkoxyalkylating 5,5-diphenyl-barbituric acid with methoxymethyl methanesulfonate in the presence of di-isopropyl ethyl amine and isolating the resultant N,N?-bismethoxymethyl-5,5-diphenyl-barbituric acid. The invention also contemplates the novel compounds N-methoxymethyl-5,5-diphenylbarbituric acid, N-methoxymethyl ethosuximide, and N-methoxymethyl glutethimide, and a method comprising administering them to a patient.