Abstract: Disclosed are uses of carboxamide, sulfonamide and amine compounds for the treatment and amelioration of disorders and conditions related to oxidative stress, mitochondrial dysfunction, free radical damage and metabolic inefficiency, among others. Also described are methods for increasing exercise endurance, exercise efficiency and aerobic workload using the compounds described herein.

Abstract: Survival of, or axon regeneration in a lesioned mature central nervous system (CNS) neuron is promoted by (a) contacting the neuron with a therapeutically effective amount of an exogenous activator of protein translation; and (b) detecting the resultant promotion of the survival of, or axon regeneration in the neuron.

Abstract: Hydrogenated pyrido[4,3-b]indoles, pyrido[3,4-b]indoles and azepino[4,5-b]indoles are described. The compounds may bind to and are adrenergic receptor ?2B antagonists. The compounds may also bind to and antagonize adrenergic receptor ?1B. The compounds may find use in therapy, e.g., to (i) reduce blood pressure and/or (ii) promote renal blood flow and/or (iii) decrease or inhibit sodium reabsorption. The compounds may also be used to treat diseases or conditions that are, or are expected to be, responsive to a decrease in blood pressure. Use of the compounds to treat cardiovascular and renal disorders is particularly described.

Abstract: Substituted pyridoindoles for incorporation in pharmaceutical compositions employed in the treatment of various diseases correspond to formula (I) wherein R1 is H or optionally substituted alkyl; R2, R3, R4 are each independently selected from H, —O-alkyl, —S-alkyl, alkyl, halo, —CF3, and —CN; G is —CR12R13—NR5— or —NR5—CR12R13; R5 is H, optionally substituted alkyl, optionally substituted heterocycle, —C(?O)—R6, —C(?O)—O—R7, or —C(?O)—NR19R20; R6 and R7 are each optionally substituted alkyl or optionally substituted heterocycle; R8, R9, R10, R11, R12, R13, R19 and R20 are each independently selected from H or optionally substituted alkyl; R14 and R15 are each independently H or halogen; L is —CH2—O—, —CH2CH2—, —CH?CH— or a bond; and B is aryl or heteroaryl or cycloalkyl; with the proviso that, when L is a direct bond, B cannot be unsubstituted heteroaryl or heteroaryl monosubstituted with fluorine.

Abstract: This disclosure is directed to pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. The compounds may bind to and antagonize receptor ?2B, ?1B or ?2A. The compounds may find use in therapy, e.g., to (i) reduce blood pressure and/or (ii) promote renal blood flow and/or (iii) decrease or inhibit sodium reabsorption, or to regulate blood glucose level, increase insulin secretion and treat diseases or conditions that are, or are expected to be, responsive to an increase in insulin production. The compounds may also be used to treat diseases or conditions that are expected to be responsive to a decrease in blood pressure. Use of the compounds to treat cardiovascular, renal disorders or type 2 diabetes is particularly described.

Abstract: Provided are methods of treating an overactive bladder in a patient which include: administering a Myosin II ATPase inhibitor compound; or administering an X group and Y group substituted (3a-hydroxy-1-phenyl-1,2,3,3a-tetrahydro-4H-pyrollo[2, 3b] quinolin-4-one) compound of Formula 1 or administering an X group and Y group substituted (3a-hydroxy-1-phenyl-1,2,3,3a-tetrahydro-4H-pyrollo[2,3b] quinolin-4-one) compound of Formula II; or administering pharmaceutically-acceptable salts, racemic mixtures, enantiomers, or prodrugs of said compounds, useful in their active form as inhibitors of Myosin H ATPase related to over-active bladder. Optionally the compounds are administered intervesicularly into the bladder. Also provided are pharmaceutical compositions comprising said compounds useful in their active form, as methods of treating a patient suffering from an over-active bladder related to inhibition of Myosin II ATPase.

Abstract: The invention relates to compositions, methods, and kits for treating subjects infected by or at risk of infection with a DNA virus (e.g., a JC Virus or a BK virus). Aspects of the invention are useful to prevent or treat DNA virus associated conditions (e.g., PML) in subjects that are immunocompromised. Compositions are provided that inhibit intracellular replication of DNA viruses.

Abstract: Compounds that are specifically toxic to cancer stem cells are disclosed.

Abstract: This disclosure relates to new tetracyclic compounds that may be used to modulate a histamine receptor in an individual. The compounds in one embodiment are tetracyclic[4,3-b]indoles. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

Abstract: This application relates to a compound of Formula ! (or a pharmaceutically acceptable salt thereof) as defined herein, pharmaceutical compositions thereof, and its use as an antagonist of receptor CRTH2, as well as a process for its preparation and intermediates therefor.

Abstract: Compounds of the formula (I) useful as 11-Beta Hydroxysteroid Dehydrogenase Inhibitors

Abstract: The present invention relates to cosmetic or dermatological compositions containing PQQ or its esters, methods of treating or promoting skin changes by topical application of these compositions, and methods of synthesis of PQQ esters. The PQQ ester-containing compositions of the present invention are unexpectedly effective in treating skin, particularly with respect to skin tolerance. When included in a topical composition, the PQQ esters of the present invention have an antioxidant effect that is useful in treating a skin change.

Abstract: Disclosed is an antidepressant, neuroprotectant, amyloid ? deposition inhibitor, or age retardant composition containing a heterocyclic compound having the general formula (I):

Abstract: The present invention is directed to novel aminopyrrolidines of formula I pharmaceutically acceptable salts thereof, metabolites thereof, isomers thereof, stereoisomers thereof or pro-drugs thereof, wherein the variables are as defined herein. The compounds of formula (I) are useful as chemokine receptor antagonists and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, cancers.

Abstract: Beta-carboline derivatives of structural formula I are selective antagonists of the somatostatin subtype receptor 3 (SSTR3) and are useful for the treatment of Type 2 diabetes mellitus and of conditions that are often associated with this disease, including hyperglycemia, insulin resistance, obesity, lipid disorders, and hypertension. The compounds are also useful for the treatment of depression and anxiety.

Abstract: Disclosed is a new use for sphingosine-1-phosphate (S1P) receptor agonists in the treatment of progressive dementia or brain degenerative diseases.

Abstract: Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, —C(?O), —S(?O)2—, —C(?O)O—, —C(O)NR3—, —C(?S)—NR3, —C(?NH)NR3 or —S(?O)2NR3— wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula —X2-Q1- or -Q1-X2— wherein X2 is —O—, S— or NRA— wherein RA is hydrogen or optionally substituted C1-C3 alkyl, and Q1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic r

Abstract: Compound of formula (I) and methods of treating disorders by administering a compound of formula (I) are described herein. Examples of disorders include neoplastic disorders, fat-cell related disorders, neurodegenerative disorders, and metabolic disorders.

Abstract: Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a neurological disease, traumatic brain injury, stroke, malaria, an autoimmune disease, autism, and inflammation, also are disclosed.

Abstract: The present invention provides compounds of formula I: or a pharmaceutically acceptable salt, tautomer, or stereoisomer, thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a Plasmodium parasite, such as malaria.

Abstract: Hydrogenated pyrido[4,3-b]indoles, pyrido[3,4-b]indoles and azepino[4,5-b]indoles are described. The compounds may bind to and are antagonists of the adrenergic receptor a2A. The compounds may also bind to and are an antagonist of the adrenergic receptor ?2B; or the compounds are not antagonists of the adrenergic receptor ?2? and the compounds are administered in conjunction with a second agent that reduces, or is expected to reduce, blood pressure in an individual. The compounds may find use in therapy, e.g., to regulate blood glucose level, increase insulin secretion and treat diseases or conditions that are, or are expected to be, responsive to an increase in insulin production. Use of the compounds to treat type 2 diabetes is particularly described.

Abstract: Bridged bicyclic aryl or heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed.

Abstract: An agent for the prophylaxis or treatment of stress urinary incontinence, which contains a substance that activates a serotonin 5-HT2C receptor, an agent for the prophylaxis or treatment of stress urinary incontinence, which contains a substance that stimulates an androgen binding site, and a method of screening for a drug for the prophylaxis or treatment of abdominal pressure incontinence, which includes electrostimulating the abdominal muscles or a nerve controlling them of an animal to increase the abdominal pressure, and measuring the leak point pressure at that time.

Abstract: New heterocyclic compounds that may be used to modulate a histamine receptor in an individual are described. Pyrido[4,3-b]indoles are described, as are pharmaceutical compositions comprising the compounds and methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

Abstract: The disclosure relates to methods for treating hyperlipidemia in a mammal. The present disclosure also relates to methods for treating and/or controlling obesity in a mammal. The methods involve combination therapies using a microsomal triglyceride transfer protein (MTP) inhibitor (for example, AEGR-733 and implitapide) and a DGAT inhibitor (for example, JTT-553 or PF-04415060). Co-administration of the MTP inhibitor with the DGAT inhibitor produces a therapeutic benefit, for example, a reduction in the concentration of cholesterol and/or triglycerides in the blood stream, but with fewer or reduced side effects than when higher dosages of the MTP inhibitor are used during monotherapy to provide the same or similar therapeutic benefit.

Abstract: The present invention relates to compounds of formulas III and V that are useful as pharmaceutical agents, particularly as autophagy inhibitors.

Abstract: The present invention relates to antibacterial compounds of formula (I) wherein “----” is a bond or is absent, V is CH, CR6 or N; R0 is H or, if “----” is a bond, may also be alkoxy; R1 is cyano, alkyl, or ethynyl; U is CH or N when “----” is a bond, or, if “----” is absent, U is CH2, NH or NH9; R2 is H, alkylcarbonyl or CH2—R3; R3 is H, alkyl or hydroxyalkyl; R4 is H or, if n is not 0 and R5 is H, may also be OH; R5 is H, alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, carboxy or alkoxycarbonyl; R6 is hydroxyalkyl, carboxy, alkoxycarbonyl or —(CH2)q—NR7R8, q being 1, 2 or 3 and each of R7 and R8 independently being H or alkyl or R7 and R8 forming with the N atom bearing them a ring; R9 is alkyl or hydroxyalkyl; A is —(CH2)p—, —CH2CH2CH(OH)— or —COCH2CH(OH)—; G is substituted phenyl or G1 or G2, wherein Q is O or S and X is CH or N; and Y1, Y2 and Y3 may each be CH or N; and n is 0 when A is —CH2CH2CH(OH)— or —COCH2CH(OH)—, and n is 0, 1 or 2 when A is —(CH2)p—, p being 1, 2, 3 or 4, with the proviso that the s

Abstract: The present invention provides a computer-assisted method of generating a protonophore requiring the use of a computer including a processor. The method includes: designing the protonophore, calculating, using the processor, an estimated protonophoric activity; producing the protonophore if the estimated protonophoric activity corresponds to an U50 of about 20 ?M or less; and determining the uncoupling activity of the protonophore. The present invention also provides novel protonophores that meet the above requirement and their methods of use.

Abstract: An object of the present invention is to provide a composition that enables extension of the concentration range in which pyrroloquinoline quinone exerts cell growth-promoting function, and an efficient method of producing the composition. According to the present invention, there is provided a liposome composition comprising liposomes individually containing pyrroloquinoline quinone or a salt thereof and sugar, 50% or more of the liposomes having a particle diameter in the range of from 1 to 10 ?m, and a method of producing the composition.

Abstract: Bridged bicyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed.

Abstract: Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure: enantiomers, diastereomers, solvates, salts, tautomers or prodrugs thereof wherein, A, W, X, Y and R1 are defined herein.

Abstract: Substituted pyridoindoles for incorporation in pharmaceutical compositions employed in the treatment of various diseases correspond to formula (I) wherein R1 is H or optionally substituted alkyl; R2, R3, R4 are each independently selected from H, —O-alkyl, —S-alkyl, alkyl, halo, —CF3, and —CN; G is —CR12R13—NR5— or —NR5—CR12R13; R5; is H, optionally substituted alkyl, optionally substituted heterocycle, —C(?O)—R6, —C(?O)—O—R7, or —C(?O)—NR19R20; R6 and R7 are each optionally substituted alkyl or optionally substituted heterocycle; R8, R9, R10, R11, R12, R13, R19 and R20 are each independently selected from H or optionally substituted alkyl; R14 and R15 are each independently H or halogen; L is —CH2—O—, —CH2CH2—, —CH?CH— or a bond; and B is aryl or heteroaryl or cycloalkyl; with the proviso that, when L is a direct bond, B cannot be unsubstituted heteroaryl or heteroaryl monosubstituted with fluorine.

Abstract: Physical crystal structures of a compound of the formula I: are provided including the free base monohydrate thereof (form H-1) and the hydrochloric acid salt thereof, including hydrochloric acid salt containing 0.75 equivalent of H2O (form H0.75-3) and hydrochloric acid salt containing 2 equivalents of H2O (form H2-1), and hydrochloric acid salt Pattern P-5, preferably in substantially pure form, and other forms as described herein, pharmaceutical compositions containing structures of compound I or IA, processes for preparing same, intermediates used in preparing same, and methods of treating diseases such as diabetes using such structures.

Abstract: The present invention pertains generally to methods of preparing certain 9-(arylalkyl)-1,2,3,4-tetrahydro-?-carboline compounds and their analogues, and especially to methods of preparing dimebon. The present invention also pertains to methods of preparing certain intermediate compounds which find use in the synthesis of the 9-(arylalkyl)-1,2,3,4-tetrahydro-?-carboline compounds.

Abstract: Improved medical devices and methods are provided comprising an anabolic agent for healing an injury. These improved medical devices and methods can enhance healing in injuries from traumatic soft tissue injury, surgical injuries, burn, traumatic brain injuries, musculotendinous injuries, musculoskeletal conditions, bone injury or other injuries or maladies, which can be chronic or non-chronic in origin. In some embodiments, the medical device comprises a drug depot that releases the anabolic agent over at least 2 days to enhance healing of an injury.

Abstract: The present invention is directed to a composition including N-Coumaroyldopamine and a catechol-o-methyltransferase (COMT) inhibitor for promoting weight loss in a user.

Abstract: Imidazopyridine, imidazoquinoline, and imidazonaphthyridine compounds having an amide substituent at the 1-position, pharmaceutical compositions containing the compounds, intermediates, and methods of making and methods of use of these compounds as immunomodulators, for modulating cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases are disclosed.

Abstract: The present invention is directed to isoindolone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

Abstract: Methods are provided for identifying molecules that can be used to positively and negatively manipulate quorum-sensing-mediated communication to control bacterial behavior. Small-molecule antagonists that disrupt quorum-sensing-mediated activities are identified. Methods are provided for disrupting detection of acyl-homoserine lactone autoinducer in Gram-negative bacteria by contacting the bacteria with the antagonists. Methods of inhibiting quorum sensing-mediated activity in Gram-negative bacteria are provided wherein the activity is pathogenicity, bioluminescence, siderophore production, type III secretion, or metalloprotease production.

Abstract: This invention relates generally to stimulating neurogenesis (e.g., post-natal neurogenesis, e.g., post-natal hippocampal neurogenesis) and protection from neuron cell death.

Abstract: In one embodiment, the present application discloses 2-aza-, 2-oxa- and 2-thia-2,3-dihydro-6-azaphenalene compounds and compositions, and methods for treating a neurological disease in a patient in need thereof using the compounds and compositions as disclosed herein.

Abstract: Compound of formula (I) in which R1, R2 and R3 are defined in the following description, and the pharmaceutically acceptable acid-addition or base-addition salts thereof. The invention also relates to a process and an intermediate for preparing it, and to a pharmaceutical composition comprising it. The invention also relates to the use of a novel 2H-pyrrolo[3,4-c]quinoline compound for preparing a pharmaceutical composition that is active in the treatment of disturbances of the serotoninergic system.

Abstract: The invention is directed to ?-carboline sulphonylurea derivatives as EP4 receptor antagonists useful for the treatment of EP4 mediated diseases or conditions, such as acute and chronic pain, inflammation, osteoarthritis, and rheumatoid arthritis. Pharmaceutical compositions and methods of use are also included.

Abstract: Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof, formula (I) are useful as kinase modulators, including Btk modulation.

Abstract: Hydrogenated pyrido[4,3-b]indoles, pyrido[3,4-b]indoles and azepino[4,5-b]indoles are described. The compounds may bind to and are adrenergic receptor ?2B antagonists. The compounds may also bind to and antagonize adrenergic receptor ?1B. The compounds may find use in therapy, e.g., to (i) reduce blood pressure and/or (ii) promote renal blood flow and/or (iii) decrease or inhibit sodium reabsorption. The compounds may also be used to treat diseases or conditions that are, or are expected to be, responsive to a decrease in blood pressure. Use of the compounds to treat cardiovascular and renal disorders is particularly described.

Abstract: The invention provides methods for reducing growth and/or metastasis of androgen-independent (castration resistant) prostate cancer in a tissue in an animal. In one embodiment the method comprises administering to the animal a therapeutically effective amount of a compound that reduces the number of B cells, and/or the function of B cells, in the tissue. In yet another embodiment, the invention provides methods for reducing androgen-induced growth of prostate epithelial cells in prostate tissue in an animal. In one embodiment, the method comprises administering to the animal a therapeutically effective amount of a compound that reduces the number of B cells, and/or the function of B cells, in the tissue.

Abstract: Provided are bis-quaternary ammonium cyclophane compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and or gastrointestinal tract disorders.

Abstract: The invention provides tricyclic sulfonamide compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.

Abstract: There is provided a pharmaceutical agent, food, or beverage for treating or preventing a disease or condition that can be ameliorated by inhibiting serotonin reuptake, comprising a clinically-effective amount of (1S,3S)-1-methyl-1,2,3,4-tetrahydro-?-carboline-3-carboxylic acid.

Abstract: Compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.