Abstract: There is provided a transnasal anticonvulsive pharmaceutical composition including a poorly soluble anticonvulsant. The anticonvulsive pharmaceutical composition comprising a poorly soluble anticonvulsant as an active component, which is transnasally spray-administered, comprises diethylene glycol monoethyl ether and fatty acid ester, wherein the fatty acid ester is selected from the group consisting of caprylocaproyl polyoxylglyceride, isopropyl palmitate, oleoyl polyoxylglyceride, sorbitan monolaurate 20, methyl laurate, ethyl laurate, and polysorbate 20. Also, the anticonvulsive pharmaceutical composition comprising a poorly soluble anticonvulsant as an active component, which is transnasally spray-administered, comprises diethylene glycol monoethyl ether, fatty acid ester, methylpyrrolidone, water and alcohol. Therefore, the transnasal anticonvulsive pharmaceutical composition may be useful to highly enhance the bioavailability of the poorly soluble anticonvulsant.

Abstract: The present invention relates to methods for the prevention and/or treatment of memory impairment and for improving memory and particularly to methods for the prevention and/or treatment of memory impairment and improving memory comprising administering an agent that decreases activity of a GABAA receptor. The present invention also relates the use of an agent that decreases activity of a GABAA receptor for preventing or treating a memory deficit and for improving memory.

Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

Abstract: Described herein are methods for improving engraftment of hematopoietic cells in an individual following hematopoietic progenitor cell transplantation (e.g., via bone marrow or cord blood transplantation). Methods for increasing hematopoietic progenitor cell proliferation in individuals with bone marrow aplasia are also described. The methods involve administering an agent that inhibits adipogenesis, adipocyte growth, adipocyte differentiation and/or adipocyte proliferation.

Abstract: The present invention relates to substituted benzo-pyrido-triazolo-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-pyrido-triazolo-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds or pharmaceutical compositions to subjects in need thereof.

Abstract: This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those benzodiazepine derivatives and methods of using those derivatives or compositions in treating central nervous system (CNS) disorders with cognitive impairment that are responsive to agonists of ?5 subunit containing GABAA receptor, e.g., age-related cognitive impairment, Mild Cognitive Impairment (MCI), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia and cancer-therapy-related cognitive impairment.

Abstract: The present invention relates to apoptosis signal-regulating kinase 1 (“ASK1”) inhibiting compounds of the formula wherein the variables are as defined herein. The invention also relates to pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

Abstract: Disclosed are N-1-cyano-2-(phenyl)ethyl)-2-azabicyclo[2.2.1]heptane-3-carboxamides of formula I and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of respiratory diseases.

Abstract: The present invention relates to substituted benzo-pyrimido-tetrazolo-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-pyrimido-tetrazolo-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: Methods for treating a central nervous system (CNS) injury in a subject are provided. As of the methods include administering to the subject an effective amount of gamma aminobutyric acid (GABA) receptor signaling inhibitor to treat the subject for the CNS injury. Also provided are compositions useful in embodiments of the methods. Methods and compositions of the invention find use in the treatment of a variety of different CNS injuries, including but not limited to, treating a subject for CNS injury associated with the occurrence of stroke.

Abstract: This application discloses liquid compositions for administration to a patient comprising midazolam and a pharmaceutically acceptable carrier, wherein the pH of the composition is about 6 or higher, the composition comprises less than about 200 mg/ml cyclodextrin, and at least about 50% of the midazolam is present in solution. Uses of these compositions are also disclosed.

Abstract: The disclosure provides compounds of formula (I), including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.

Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

Abstract: Diseases and conditions associated with tissues of the body, including but not limited to tissues in the eye, can be effectively treated, prevented, inhibited, onset delayed, or regression caused by administering therapeutic agents to those tissues. Described herein are liquid formulations which deliver a variety of therapeutic agents, including but not limited to rapamycin, to a subject for an extended period of time; liquid formulations which form a non-dispersed mass when placed in an aqueous medium of a subject; non-dispersed mass-forming liquid formulations which form a gel or gel-like substance in an aqueous medium; liquid formulations, comprising a therapeutic agent and a plurality of polymers; and methods for delivering therapeutic agents to a subject for an extended period of time using the liquid formulations.

Abstract: Described herein are ?3 or ?2 or ?2/?3 GABAergic receptor subtype selective ligands, pharmaceutical compositions, and methods of use of such ligands and compositions in treatment of anxiety disorders, epilepsy and schizophrenia with reduced sedative and ataxic side effects. In embodiments, such as ?3 or ?2 or ?2/?3 GABAergic receptor subtype selective ligands lack ester linkages and may be thus relatively insensitive to hydrolysis by esterases.

Abstract: Compounds having inverse agonist functional selectivity for GABAA receptors containing the ?5 subunit for use as a medicament in the treatment of cognitive impairments in subjects suffering from Down syndrome. The use of these compounds is disclosed. Pharmaceutical compositions for such treatment can comprise these compounds or suitable pharmaceutically acceptable salt thereof, a polyethoxylated castor oil and dimethyl sulfoxide (DMSO). Methods are disclosed for enhancing cognitive function, or treating or lessening the severity of cognitive impairments, in subjects suffering from Down syndrome by administering to a subject in need thereof a pharmaceutically effective amount of one or more of these compounds.

Abstract: A class of compounds that inhibit Hepatitis C Virus (HCV) is disclosed, along with compositions containing the compound, and methods of using the composition for treating individuals infected with HCV.

Abstract: The present invention is concerned with a method of treating Alzheimer's disease by administering a therapeutically effective amount of a substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine of formula I wherein R1, R2, and R3 are as defined herein, and their pharmaceutically acceptable acid addition salts. The invention also provides novel compounds of formula I-A and pharmaceutical compositions containing them.

Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

Abstract: Fused [1,2]imidazo[4,5-c] ring compounds (e.g., imidazo[4,5-c]quinolines, 6,7,8,9-tetrahydroimidazo[4,5-c]quinolines, imidazo[4,5-c]naphthyridines, and 6,7,8,9-tetrahydroimidazo[4,5-c]naphthyridines) with a —CH(—X1—R1)— group in the fused ring at the 1-position of the imidazo ring, pharmaceutical compositions containing the compounds, intermediates, methods of making the compounds, and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases, are disclosed.

Abstract: Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

Abstract: Provided herein are fused imidazolyl compounds, methods of synthesis, and methods of use thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including, e.g., neurological disorders and metabolic disorders. Compounds provided herein inhibit the activity of histamine H3 receptors and modulate the release of various neurotransmitters, such as, e.g., histamine, acetylcholine, norepinephrine, and dopamine (e.g. at the synapse). Pharmaceutical compositions containing the compounds and their methods of use are also provided herein.

Abstract: S-t-butyl protected cysteine di-peptide analogs and related compounds and methods of using these compounds for the treatment of diseases and/or conditions, including but not limited to diseases and/or conditions of Central Nervous System (CNS).

Abstract: The present invention relates to the pharmaceutical use of selective GABA A ?5 negative allosteric modulators for the treatment, prevention and/or delay of progression of central nervous system (CNS) conditions related to excessive GABAergic inhibition in the brain.

Abstract: The present invention relates to substituted benzo-imidazo-pyrido-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-imidazo-pyrido-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: Method for therapeutic treatment of inflammatory bowel disease, including Crohn's disease, comprising administering to a patient in need thereof a therapeutically effective amount of a composition comprising a retinoid as an active ingredient to treat the inflammatory bowel disease, the retinoid being selected from the group consisting of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl]benzoic acid, 4-[(3,5-bis-trimethylsilylphenyl)carboxamido]benzoic acid, 4-[2,3-(2,5-dimethyl-2,5-hexano)dibenzo[b,f][1,4]thiazepin-11-yl]benzoic acid, and 4-(5H-7,8,9,10-tetrahydro-5,7,7,10,10-pentamethylbenzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid.

Abstract: Described herein are methods for improving engraftment of hematopoietic cells in an individual following hematopoietic progenitor cell transplantation (e.g., via bone marrow or cord blood transplantation). Methods for increasing hematopoietic progenitor cell proliferation in individuals with bone marrow aplasia are also described. The methods involve administering an agent that inhibits adipogenesis, adipocyte growth, adipocyte differentiation and/or adipocyte proliferation.

Abstract: The present invention relates to a tetracyclic fused heterocyclic compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

Abstract: The present invention relates to compounds having general Formula (I) or a pharmaceutically acceptable salt thereof. The present invention also relates to pharmaceutical compositions comprising said compounds and the use of these derivatives to modulate glucocorticoid receptor activity.

Abstract: Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein A, B, D, E, G, R1, R2, R3, R4, R5, R6 and R7 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Abstract: Provided herein are fused imidazolyl compounds, methods of synthesis, and methods of use thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders and metabolic disorders. Compounds provided herein inhibit the activity of histamine H3 receptors and modulate the release of various neurotransmitters, such as histamine, acetylcholine, norepinephrine, and dopamine (e.g. at the synapse). Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

Abstract: Compounds of the formula (I) wherein A, B, D, M, Ar, W, X, Y, Z and R1 are as defined herein, are useful in the prevention and treatment of hepatitis C infections. The compounds, their preparation, pharmaceutical compositions containing them and their use in medicine are disclosed.

Abstract: Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes.

Abstract: Provided herein are fused imidazolyl compounds, methods of synthesis, and methods of use thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders and metabolic disorders. Compounds provided herein inhibit the activity of histamine H3 receptors and modulate the release of various neurotransmitters, such as histamine, acetylcholine, norepinephrine, and dopamine (e.g. at the synapse). Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

Abstract: A thienotriazolodiazepine compound of the following formula (I) a pharmaceutical agent containing the compound as an active ingredient, and a production intermediate and a production method of the thienotriazolodiazepine compound. Since this compound has an inhibitory action on costimulatory signal from CD28 on T cell, it is useful for the prophylaxis or suppression of rejection reaction in transplantation of organ or bone marrow and the like, and the prophylaxis or treatment of autoimmune diseases or allergic diseases.

Abstract: The present invention provides compositions for the intranasal administration of zolpidem or a pharmaceutically acceptable salt thereof. Preferred compositions of the invention are in the form of aqueous solutions. Optionally the compositions of the invention comprise a cyclodextrin and/or chitosan, a salt or derivative thereof or a salt of a derivative of chitosan. The compositions can be used for the treatment or prevention insomnia or the treatment of neurological disorders such as those arising from brain trauma, stroke and spinocerebellar ataxia or in the treatment of Parkinson's disease.

Abstract: The present invention relates to substituted benzo-pyrido-triazolo-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-pyrido-triazolo-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds or pharmaceutical compositions to subjects in need thereof.

Abstract: This invention is directed to tricyclic spiro-oxindole derivatives of formula (I), wherein j, k, m, n, w, q, Y, Q, X, R1, R2 and R3 are as defined herein, as a stereoisomer, enantiomer, tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof, which are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain. Pharmaceutical compositions comprising the compounds and methods of preparing and using the compounds are also disclosed.

Abstract: The present invention relates to the use of staurosporines derivatives for the preparation of a drug for the treatment of diseases involving deregulated FLT3 receptor tyrosine kinase activity, especially for the curative and/or prophylactic treatment of leukemias and myelodysplastic syndromes, and to a method of treating diseases involving deregulated FLT3 receptor tyrosine kinase activity.

Abstract: Methods for treating a central nervous system (CNS) injury in a subject are provided. Aspects of the methods include administering to the subject an effective amount of gamma aminobutyric acid (GABA) receptor signaling inhibitor to treat the subject for the CNS injury. Also provided are compositions finding use in embodiments of the methods. Methods and compositions of the invention find use in the treatment of a variety of different CNS injuries, including but not limited to, treating a subject for CNS injury associated with the occurrence of stroke.

Abstract: A class of macrocyclic compounds of formula (I), wherein R7, A, Ar, B, D, F, M, Q1, Q2, W, X, Y and Z are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection.

Abstract: The present invention relates to substituted benzo-pyrimido-tetrazolo-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-pyrimido-tetrazolo-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: Compounds of formula I: (wherein variables A1, A2, A3, A4, A5, A6, A7, B1, B2, B3, B4, D1, D2, E1, E2, E3, E4, E5, G1, G2, R6, T, U, V, W, X, Y and Z are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Abstract: The present application provides methods and compositions that can be used to treat persistent pain and to identify compounds that can be used for treating persistent pain. More specifically, agonists of members of the Mrgpr receptor family, particularly agonists of MrgprX1, can identified and screened for use in treating persistent pain, such as pain caused by inflammation or nerve injury.

Abstract: Methods of treating an SCD-mediated skin disorder or condition in a mammal, preferably a human include administering to a mammal in need thereof a compound of formula (I): where x, y, W, V, R2, R3, R4, R5, R6, R6a, R7, R7a, R8, R8a, R9 and R9a are defined herein.

Abstract: Compounds that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.

Abstract: The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nAChR), activation of nAChRs, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds (indazoles and benzothiazoles), which act as ligands for the ?7 nAChR subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

Abstract: Provided herein are fused imidazolyl compounds, methods of synthesis, and methods of use thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including, e.g., neurological disorders and metabolic disorders. Compounds provided herein inhibit the activity of histamine H3 receptors and modulate the release of various neurotransmitters, such as, e.g., histamine, acetylcholine, norepinephrine, and dopamine (e.g. at the synapse). Pharmaceutical compositions containing the compounds and their methods of use are also provided herein.

Abstract: Methods for treatment of disease-induced ataxia and non-ataxic imbalance are disclosed. The methods involve treating a patient with a compound having nicotinic acetylcholine receptor activity.

Abstract: Piperazine, [1,4]diazepane, [1,4]diazocane, and [1,5]diazocane fused imidazo ring compounds (i.e., imidazoquinolines, tetrahydroimidazoquinolines, imidazonaphthyridines, tetrahydroimidazonaphthyridines, and imidazopyridines), pharmaceutical compositions containing the compounds, intermediates, methods of making, and methods of use of these compounds as immunomodulators, for inducing or inhibiting cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases are disclosed.