Abstract: The present disclosure relates to the use of 2-iminobiotin for treating brain cell injury, in particular in adults. The treatment may be used for the treatment of cerebral hypoxia-ischemia and/or reperfusion injury, including one or more symptoms thereof. Provided are methods of treatment comprising administering a therapeutically effective dose of 2-iminobiotin to an individual in need thereof.

Abstract: The present disclosure relates to the use of 2-iminobiotin for treating brain cell injury, in particular in adults. The treatment may be used for the treatment of cerebral hypoxia-ischemia and/or reperfusion injury, including one or more symptoms thereof. Provided are methods of treatment comprising administering a therapeutically effective dose of 2-iminobiotin to an individual in need thereof.

Abstract: The present disclosure relates to the use of 2-iminobiotin for treating brain cell injury, in particular in adults. The treatment may be used for the treatment of cerebral hypoxia-ischemia and/or reperfusion injury, including one or more symptoms thereof. Provided are methods of treatment comprising administering a therapeutically effective dose of 2-iminobiotin to an individual in need thereof.

Abstract: Compounds for the treatment of bacterial and parasitic infections which are hybrid compounds of compounds having antibacterial or antiparasitic activity and compounds that decrease the absorption of the hybrid compound from the gastrointestinal tract. The compounds are preferably for use against C. difficile infections and comprise a hybrid molecule of an anti-C. difficile compound such as a nitroimidazole and a tetramic acid derivative.

Abstract: Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including those mediated by inhibition of fatty acid synthase (FASN) enzyme, such as, cancer, obesity or related discorders, and liver related disorders. Such compounds are represented by formula (I) as follows: wherein L1, a, b, m, n, R1, R2, R3, R4, and R5 are defined herein.

Abstract: Provided are tris-quaternary ammonium 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 novel, water-soluble 2-aminoimidazoline derivatives having general Formula (I) as well as some precursors of Formula (I), which are very potent inducers of G2/M cell cycle arrest. In treated tumor cells, compounds of Formula (I) give gene expression profile distinct from known antimitotic agents. The invention also provides methods for preparing the compounds, and methods of using the compounds for the treatment of cancer or other mammalian diseases characterized by undesirably high levels of cell proliferation. The compounds of the invention are also expected to have utility as research tools.

Abstract: The invention provides novel, water-soluble 2-aminoimidazoline derivatives having general Formula (I) as well as some precursors of Formula (I), which are very potent inducers of G2/M cell cycle arrest. In treated tumor cells, compounds of Formula (I) give gene expression profile distinct from known antimitotic agents. The invention also provides methods for preparing the compounds, and methods of using the compounds for the treatment of cancer or other mammalian diseases characterized by undesirably high levels of cell proliferation. The compounds of the invention are also expected to have utility as research tools.

Abstract: The present invention relates to pyrrolidine derivatives of the formula (I), or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such pyrrolidine derivatives, and the use of such pyrrolidine derivatives for therapeutic purposes. The pyrrolidine derivatives are GlyT1 inhibitors.

Abstract: The invention relates to inhibition of SDF-1? expression in subacromial bursa cells by CXCR-4 inhibitors. Bursal cell migration in response to SDF-? stimulation is also decreased in the presence of CXCR4 inhibitors. Accordingly, provided are methods for treating or ameliorating a musculoskeletal disorder.

Abstract: Disclosed are compounds of Formula I or pharmaceutically acceptable salts thereof, wherein X1, X2, X3, R1, R2 and R3 are as described in this application, and methods of using the compounds in the treatment of cancer.

Abstract: Provided are tris-quaternary ammonium compounds which are modulators of nicotinic acetylocholine 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 present invention relates to spirocyclic acylguanidines and their use as inhibitors of the ?-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of ?-amyloid aggregates.

Abstract: The invention provides compounds represented by the formula I, each of which compounds may have sphingosine-1-phosphate receptor agonist and or antagonist biological activity: and wherein the variables Y, R4, n, o, A, A1, A2, X, Z, R1, R3, R2, p, q and r are as defined in the specification.

Abstract: Methods and products for treating or preventing erythema or a symptom associated with erythema in a subject are described. The methods involve topically applying to an affected skin area a topical aqueous gel composition comprising about 0.01% to about 10% by weight of at least one ?-adrenergic receptor agonist and a pharmaceutically acceptable carrier.

Abstract: Topoisomerase II alpha (topo II?) is exported from the cell nucleus in human myeloma cells by a chromosome-maintenance protein-1 (CRM1)-dependent mechanism, resulting in topo II inhibitor resistance. The nuclear export signal (NES) of topo II? is unique, making it a potential target for small molecule inhibitors. Small molecules NES inhibitors were identified, which inhibited binding of topo II? to the export receptor CRM1. Inhibition was specific to topo II? as p53 trafficking was unaffected along with topo II? protein expression and function (decatenation). These topo II?-specific nuclear export inhibitors may potentially lead to a new approach in circumventing drug resistance in multiple myeloma. The compounds provide a protocol for treating multiple myeloma or an oncogenic disease. Further, the topoisomerase II nuclear export signal inhibitor may be combined with a topoisomerase II inhibitor.

Abstract: Biocompatible intraocular implants include an alpha-2 adrenergic receptor agonist and a polymer associated with the alpha-2 adrenergic receptor agonist to facilitate release of the alpha-2 adrenergic receptor agonist into an eye for an extended period of time. The alpha-2 adrenergic receptor agonist may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. The implants can be placed in an eye to treat one or more ocular conditions, such as an ocular vasculopathy or glaucoma, including reduction of an elevated intraocular pressure.

Abstract: A pharmaceutical composition comprising idazoxan or derivatives and their therapeutically acceptable salts, racemates, optically active isomers and polymorphs.

Abstract: Methods and products for treating or preventing erythema or a symptom associated with erythema in a subject are described. The methods involve topically applying to an affected skin area a topical aqueous gel composition comprising about 0.01% to about 10% by weight of at least one ?-adrenergic receptor agonist and a pharmaceutically acceptable carrier.

Abstract: In its many embodiments, the present invention provides a novel class of biaryl spiroaminooxazoline analogues as modulators of ?2C adrenergic receptor agonists, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more conditions associated with the ?2C adrenergic receptors using such compounds or pharmaceutical compositions.

Abstract: The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

Abstract: Provided are tris-quaternary ammonium compounds which are modulators of nicotinic acetylocholine 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: Methods, compounds, and topical formulations for treatment of telangiectasias are disclosed. The methods comprise topically applying a composition comprising an ?-adrenergic receptor agonist to telangiectatic skin. Amelioration of telangiectasia symptoms begins within minutes after topical application of a disclosed composition. A single application can significantly lessen telangiectasia discoloration for at least about 2 hours.

Abstract: The present invention relates to a method for treating a disorder selected from depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders which comprises administering to an individual a therapeutically effective amount of a compound of formula I wherein R1, R2, Q, W, X, Y, m, and n are as defined in the specification, and their pharmaceutically active salts, racemic mixtures, enantiomers, optical isomers and tautomeric forms.

Abstract: Pharmaceutical composition comprising 5 to 20% of an idazoxan salt or of idazoxan hydrate, 10 to 40% of microcrystalline cellulose, 1 to 5% of lubricant, 0.1 to 0.5% of colloidal silica and from 29.5% to 84.8% of lactose, with respect to the total mass.

Abstract: The invention provides reagents and methods for conjugating a polymer specifically to the ?-amine of a polypeptide. The invention provides monofunctional, bifunctional, and multifunctional PEGs and related polymers having a terminal thioester moiety capable of specifically conjugating to the ?-amine of a polypeptide having a cysteine or histidine residue at the N-terminus. The invention provides reactive thioester-terminated PEG polymers that have suitable reactivity with an N-terminal cysteine or histidine residue of a polypeptide to produce an amide bond between the PEG molecule and the polypeptide.

Abstract: A method of treating cancer in a subject comprising the step of administering to the subject in need thereof an effective amount of a combination of a compound that binds a nuclear export signal (NES inhibitor) on topoisomerase II? and a topoisomerase inhibitor. Twenty small molecule inhibitors (SMI) that bind to the two nuclear export sequences (NES) topo II? have been identified from the NCI database using computer-generated molecular modeling. These SMI will improve the effectiveness of topo II directed therapeutics, particularly in the treatment of diseases such as multiple myeloma (MM). In vitro apoptosis assays indicate that these drugs may be effective as single agents or in combination with currently used cancer drugs that target topo II.

Abstract: The invention relates to compounds of formula (I) wherein R1, R1a, R1b, R2, R3 and X, X1, X2, X3 have the meaning as cited in the description and the claims. Said compounds are useful as Bradykinin B1 antagonists. The invention also relates to pharmaceutical compositions, the preparation of such compounds as well as the production and use as medicament.

Abstract: The invention provides compositions and methods for treating nasal congestion through ophthalmic delivery. The provided compositions and methods utilize low concentrations of selective ?-2 adrenergic receptor agonists. The compositions preferably include brimonidine.

Abstract: Disclosed herein are methods of inhibiting the activity of Botulinum neurotoxin A metalloprotease with the compounds disclosed herein. Also disclosed are methods of treating, inhibiting or preventing intoxication caused by bacteria of at least one bacterial strain in a subject, and pharmaceutical and cosmetic compositions comprising the compounds disclosed herein.

Abstract: The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: The pyrazole derivatives of formula (I) or salts thereof modulate P2X7 receptor function and are capable of antagonizing the effects of ATP at the P2X7 receptor (P2X7 receptor antagonists). The invention also relates to the use of such compounds or salts, or pharmaceutical compositions thereof, in the treatment or prevention of disorders/diseases mediated by the P2X7 receptor, for example pain, inflammation or a neurodegenerative disease.

Abstract: This invention relates to compounds, pharmaceutical compositions and methods for the treatment of a condition mediated by CB1 receptor activity in a mammalian subject including a human, which comprises administering to a mammal in need of such treatment a therapeutically effective amount of the compound of formula (I) wherein R1, R2 and R3 are as defined in this specification.

Abstract: The present invention relates a method for treating depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders which comprises administering to an individual a therapeutically effective amount of a compound of formula I wherein R, R1, R2, A and n are as defined in the specification and to their pharmaceutically active salts. The invention also relates to novel compounds of formula I, pharmaceutical compositions containing them, and methods for their preparation.

Abstract: The present invention relates to targets of loss of imprinting (LOI) affected IGF2 gene products in pre-malignant tissues, where methods of inhibiting those targets, including IGFR1, are disclosed to prevent tumor development in subjects at risk for developing colorectal cancer (CRC). The present invention also relates to methods of identifying increased risk in developing CRC in a subject, including methods of assessing the efficacy of a chemotherapeutic regimen. Further, the present invention relates to methods for identifying anti-neoplastic agents.

Abstract: The adrenergic receptors or adrenoceptors are a family of G-protein coupled receptors split into ? and ? subclasses. The adrenoceptors have important roles in regulating a myriad of physiological conditions and their malfunction has been implicated in the pathophysiology of a number of diseases. Disclosed herein are a series of novel guanidine and 2-aminoimidazoline compounds which are ligands of the alpha2-adrenoceptor (?2-ARs) subclass of adrenergic receptors. The invention also provides for pharmaceutical compositions comprising the novel compounds. The compounds are suitable for use in the manufacture of medicaments for the treatment of ?2-ARs associated disorders, such as depression, schizophrenia, glaucoma and analgesia.

Abstract: Aspects of the present invention relate to compounds and methods useful in modulating angiogenesis and methods of treating or preventing diseases associated with angiogenesis by administering a polycationic compound. The present invention relates to methods of use and compositions for inhibiting angiogenesis-mediated disorders in mammals including animals and humans. Additionally, this invention relates to the combined use of polycations with other anti-angiogenesis agents for the treatment of different angiogenesis-mediated disorders. Additionally, those polycationic compounds can be used with various anti-inflammatory and cytotoxic agents as well as with radio-therapeutic agents in cancer patients to prevent and treat tumor growth and metastasis.

Abstract: The present invention relates to 1-arylsulfonyl-3 substituted indole or indoline derivatives having the general formula (I) (I) wherein the dotted line represents an optional bond; n is 0 or 1; m is 0-5 and Ar, R6-R11 are defined in the description. The invention further relates to pharmaceutical compositions comprising said derivatives, and to the use of these 1-arylsulfonyl-3-substituted indole or indoline derivatives in the treatment of central nervous disorders such as psychosis, schizophrenia, manic depressions, depressions, neurological disorders, cognitive enhancement, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease and Huntington's disease.

Abstract: A new class of imidazolines as 4-position acids or esters with very potent anti-inflammatory as well as antimicrobial activity is described. The synthesis of these imidazolines includes a multicomponent reaction applicable to a combinatorial synthetic approach. The combination of these two key characteristics provides an effective therapeutic drug in the treatment of septic shock as well as many other inflammatory (arthritis and asthma) and infectious disorders. The use of this novel class of non-steroidal agents as anti-inflammatory agents (for the treatment of asthma etc.), antibacterial agents and antiseptic agents is described. The compounds are also useful in the treatment of tumors (such as cancers). The imidazolines are potent inhibitors of the transcription factor NF-?B as well as potent activity against the Gram (+) bacterium B. subtillus and B. cereus with MIC values in the range of 50 ?m/mL.

Abstract: It has now been found that certain novel heterocyclic derivitives have provided unexpected insecticidal activity. These compounds are represented by formula (I): R Preferred are those compounds of formula (I) where R2 and R3 taken together is ?NCH(R6)CH(R7)N(R8)—, ?NC(R6)?C(R7)N(R8)—, or ?CHN?C(R7)N(R8)—, and tautomers thereof, and where R4 and R5 taken together is —C(R11)?C(R12)C(R13)?C(R14) 1 12, -, where R,R,R6, R7, R8, RI1, R R13, R14, and X are described. In addition, compositions comprising an insecticidally effective amount of at least one compound of formula (I), and optionally, an effective amount of at least one of a second compound with at least one insecticidally compatable carrier are also disclosed; along with methods of controlling insects comprising applying said compositions to a locus where insects are present or are expected to be present.

Abstract: The adrenergic receptors or adrenoceptors are a family of G-protein coupled receptors split into ? and ? subclasses. The adrenoceptors have important roles in regulating a myriad of physiological conditions and their malfunction has been implicated in the pathophysiology of a number of diseases. Disclosed herein are a series of novel compounds which are ligands of the alpha2-adrenoceptor (?2-ARs) subclass of adrenergic receptors. The invention also provides for pharmaceutical compositions comprising the novel compounds. The compounds are suitable for use in the manufacture of medicaments for the treatment of ?2-ARs associated disorders, such as depression and schizophrenia.

Abstract: A new class of imidazolines as 4-position acids or esters with very potent anti-inflammatory as well as antimicrobial activity is described. The synthesis of these imidazolines includes a multicomponent reaction applicable to a combinatorial synthetic approach. The combination of these two key characteristics provides an effective therapeutic drug in the treatment of septic shock as well as many other inflammatory (arthritis and asthma) and infectious disorders. The use of this novel class of non-steroidal agents as anti-inflammatory agents (for the treatment of asthma etc.), antibacterial agents and antiseptic agents is described. The compounds are also useful in the treatment of tumors (such as cancers). The imidazolines are potent inhibitors of the transcription factor NF-?B as well as potent activity against the Gram (+) bacterium B. subtillus and B. cereus with MIC values in the range of 50 ?m/mL.

Abstract: Certain atypical antipsychotic medications (particularly clozapine) or combinations of medications are useful to treat alcohol or other substance abuse, particularly in the general (non-schizophrenic) population. Generally stated, one aspect of the invention features a method of treating a patient suffering from alcohol or other substance abuse by administering to the patient medication effective to rectify an abuse-associated dysfunction in the DA-mediated brain reward circuit. A second aspect of the invention features administering medication that strongly antagonizes ?2 andrenergic receptors and weakly antagonizes dopamine D2 receptors. Preferably, the ratio of ?2 receptor blockade to D2o receptor blockade is similar to that of clozapine. The medication may be a single compound (such as clozapine or risperidone), or it may include two or more compounds which together achieve the specified function.

Abstract: A new class of imidazolines as 4-position esters with very potent anti-inflammatory as well as antimicrobial activity is described. The synthesis of these imidazolines includes a multicomponent reaction applicable to a combinatorial synthetic approach. The combination of these two key characteristics provides an effective therapeutic drug in the treatment of septic shock as well as many other inflammatory (arthritis and asthma) and infectious disorders. The use of this novel class of non-steroidal agents as anti-inflammatory agents (for the treatment of asthma, etc.), antibacterial agents, and antiseptic agents is described. The compounds are also useful in the treatment of tumors (such as cancers). The imidazolines are potent inhibitors of the transcription factor NF-?B as well as potent activity against the Gram (+) bacterium. The compositions are also useful for treating autoimmune diseases and for inhibiting rejection of organ and tissue transplants.

Abstract: Compounds and methods useful for treating and prevention of cancer, particularly hormone-dependent breast cancer. Provided are compounds of formula I: wherein X is selected from O, N, S, SO, SO2, and S(CH2)n, wherein n=1-10; R1 and R2 may be the same or different and are selected from H, OH, OCH3, OCH2CH3, OCH2C6H5, NH2, NHCH3, N(CH3)2, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, NO2, F, Cl, Br, CF3, SH, SCH3, SCH2CH3, OCOCH3, OCOC(CH3)3, OCOCH2COOH, and CN; and R3 is a nitrogen-containing heterocyclic ring. Also provided are method for treating or preventing cancer in a subject by administering a therapeutically effective amount of a heteroaryl-containing isoflavone, or a pharmaceutically acceptable salt or prodrug thereof, to a subject in need of treatment.

Abstract: This invention relates to compounds of the Formula (I): or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, TNF-? or combinations thereof.

Abstract: A pharmaceutical composition comprising idazoxan or derivatives and their therapeutically acceptable salts, racemates, optically active isomers and polymorphs.

Abstract: A new class of imidazolines as 4-position esters with very potent anti-inflammatory as well as antimicrobial activity is described. The synthesis of these imidazolines includes a multicomponent reaction applicable to a combinatorial synthetic approach. The combination of these two key characteristics provides an effective therapeutic drug in the treatment of septic shock as well as many other inflammatory (arthritis and asthma) and infectious disorders. The use of this novel class of non-steroidal agents as anti-inflammatory agents (for the treatment of asthma, etc.), antibacterial agents, and antiseptic agents is described. The compounds are also useful in the treatment of tumors (such as cancers). The imidazolines are potent inhibitors of the transcription factor NF-?B as well as potent activity against the Gram (+) bacterium. The compositions are also useful for treating autoimmune diseases and for inhibiting rejection of organ and tissue transplants.

Abstract: It has now been found that certain novel heterocyclic derivatives have provided unexpected insecticidal activity. These compounds are represented by formula (I): R Preferred are those compounds of formula (I) where R2 and R3 taken together is ?NCH(R6)CH(R7)N(R8)—, ?NC(R6)=C(R7)N(R8)-, or ?CHN?C(R7)N(R8)—, and tautomers thereof, and where R4 and R5 taken together is —C(R11)=C(R12)C(R13)=C(R14) 112, -, where R, R, R6, R7, R8, R11, R R13, R14, and X are described. In addition, compositions comprising an insecticidally effective amount of at least one compound of formula (I), and optionally, an effective amount of at least one of a second compound, with at least one insecticidally compatible carrier are also disclosed; along with methods of controlling insects comprising applying said compositions to a locus where insects are present or are expected to be present.

Abstract: A pharmaceutical composition comprising idazoxan or derivatives and their therapeutically acceptable salts, racemates, optically active isomers and polymorphs.

Abstract: A method of treating a Mycobacterium tuberculosis infection in a subject in need thereof by administering to the subject an effective amount of a cationic substituted benzofuran compound. Methods of treating microbial infections, including infections from protozoan pathogens, such as Leishmania donovani, Trypanosoma brucei rhodesiense, a Trypanosoma cruzi, and Plasmodium falciparum, and fungal pathogens, such as Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, in a subject in need thereof by administering to the subject an effective amount of a cationic substituted benzofuran compound. Methods of synthesizing novel cationic substituted benzofuran compounds and the novel compounds themselves.