Abstract: The invention encompasses the novel class of compounds represented by the formula below, which are inhibitors of the PTP-1B enzyme. The invention also encompasses pharmaceutical compositions which include the compounds shown (Formula I) above and methods of treating or preventing PTP-1B mediated diseases, including diabetes.

Abstract: The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of antimicrobials and antimicrobial-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

Abstract: The present invention relates to compounds of the Formula (I) that are useful antimicrobial agents and effective against a variety of multi-drug resistant bacteria:

Abstract: Chemical entities that modulate smooth muscle myosin and/or non-muscle myosin, pharmaceutical compositions and methods of treatment of diseases and conditions associated with smooth muscle myosin and/or non-muscle myosin are described.

Abstract: The present invention relates to the use of compounds, in which the pharmacophores of quinolone and oxazolidinone are chemically linked together through a linker that is stable under physiological conditions, for the treatment of anthrax and other infections.

Abstract: The invention relates to a compound of formula (I) wherein the substituents are as described in the specification, which are useful as farnesyl pyrophosphate synthase modulators, e.g. in the treatment of proliferative diseases, to methods of manufacturing such compounds and to intermediates thereof.

Abstract: Provided are quinolone derivatives having a lower alkyl or cycloalkyl at the 1-position; —N(R0)C(O)-lower alkylene-CO2R0, lower alkylene-CO2R0, lower alkenylene-CO2R0, —O-lower alkylene-CO2R0, —O-(lower alkylene which may be substituted with —CO2R0)-aryl or —O-lower alkenylene-CO2R0 (wherein R0 is H or lower alkyl) at the 3-position; halogen at the 6-position; and amino group substituted with a substituent group having a ring structure at the 7-position, respectively, or pharmaceutically acceptable salts thereof. Pharmaceutical composition containing the quinolone derivatives and methods of using the compositions are provided.

Abstract: The present application includes novel inhibitors of HCV, compositions containing such compounds, therapeutic methods that include the administration of such compounds.

Abstract: Low molecular weight compound exhibiting an osteogenesis-promoting action having the general formula (I) or a pharmacologically acceptable salt thereof:

Abstract: The present invention includes compositions and methods for modulating a regulator of IFNAR1. The invention includes inhibitors and activators of PERK, PTP1B, and/or PKD2 wherein inhibition, or activation, of at least one of PERK, PTP1B, and PKD2 modulates the stability of IFNAR1.

Abstract: A compound of Formula I is disclosed as follows: or a pharmaceutically acceptable salt, prodrug, solvate, or metabolite thereof, wherein R is hydrogen, P(?O)(OH)2, P(?O)(O(C1-C18)alkylene(C6-C20)aryl)2, P(?O)(OH)(OM), P(?O)(OM)2, P?O(O2M), S(?O)(OH)2, S(?O)(O(C1-C18)alkylene(C6-C20)aryl)2, S(?O)(OH)(OM), S(?O)(OM)2; M is a monovalent or divalent metal ion, or alkylammonium ion; W is (C6-C20)aryl, (C6-C20)heteroaryl, (C1-C18)alkyl(C6-C20)aryl, (C1-C18)alkyl(C6-C20)heteroaryl, hydroxy(C6-C20)aryl, hydroxy(C6-C20)heteroaryl, (C1-C18)alkoxy(C6-C20)aryl, (C1-C18)alkoxy(C6-C20)heteroaryl, (C1-C18)alkylenedioxy(C6-C20)aryl, (C1-C18)alkylenedioxy(C6-C20)heteroaryl, halo(C6-C20)aryl, halo(C6-C20)heteroaryl, (C1-C18)alkylamino(C6-C20)aryl, (C1-C18)alkylamino(C6-C20)heteroaryl, (C1-C18)cycloalkylamino(C6-C20)aryl, or (C1-C18)cycloalkylamino(C6-C20)heteroaryl, and their OR8 substutes; R5 is (C1-C18alkoxy, hydrogen, hydroxyl, O—(C1-C18)alkyl(C6-C20)aryl, halo or OR8, or R5 and R6 are (C1-C18)dioxy provided that R7 i

Abstract: The present invention provides a quinolone compound that inhibits the chronic progression of Parkinson's disease or protects dopamine neurons from disease etiology, thereby suppressing the progression of neurological dysfunction, so as to prolong the period of time until L-dopa is administered while also improving neuronal function; the quinolone compound of the invention is represented by Formula (1): wherein: R1 represents hydrogen or the like; R2 represents hydrogen or the like; R3 represents substituted or unsubstituted phenyl or the like; R4 represents halogen or the like; R5 represents hydrogen or the like; R6 represents hydrogen or the like; and R7 represents hydrogen or the like.

Abstract: A method of supplementing a diet and ameliorating oxidative stress in a mammal includes administering a pharmaceutically effective amount of lipid soluble, hydrophobic active compounds having a chemical structure: wherein R1 is an aromatic backbone and R2 is a sulfur containing ligand. Through formation of disulfide linkages other moieties can be attached to R2 converting the hydrophobic base into a water soluble entity, for ease of delivery, which can be reconverted back to the original compound by biochemical reduction in the blood stream.

Abstract: The disclosure provides, inter alia, novel bisphosphonate compounds and methods of making and using such compounds. In certain embodiments, compounds of the invention include bisphosphonates that are capable of selectively inhibiting one or more of farnesyl diphosphate synthase (FPPS), geranylgeranyl diphosphate synthase (GGPPS), and decaprenyl pyrophosphate synthase (DPPS). In preferred embodiments, compounds of the invention are capable of selectively inhibiting two or more of FPPS, GGPPS, and DPPS. In embodiments, compounds and methods of the invention demonstrate superior activity levels, such as in the anti-cancer context, immunostimulation context, and other contexts, which in several cases exceed the activity levels of previous generation bisphosphonate drugs by orders of magnitude. In embodiments, the invention provides compounds and methods in connection with research and therapeutic applications, e.g.

Abstract: The present invention is directed to pro-drugs of (E)-7-(3-(2-amino-1-fluoroethylidene)piperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, pharmaceutical compositions containing them and the use of said pro-drugs and pharmaceutical compositions as antimicrobial agents against pathogenic microorganisms, particularly against resistant microbes.

Abstract: The invention is related to a method of treating disorders associated with hepatitis C by administering to an individual a pharmaceutical composition which comprises a therapeutically effective amount of an anti-viral phosphinate compound.

Abstract: The invention is related to anti-viral phosphinate compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: The invention provides well-defined aryl and/or heteroaryl substituted indoles that are useful as spingosine-1-phosphate agonists or antagonists. As such, the compounds described herein are useful in treating a wide variety of disorders associated with modulation of sphingosine-1-phosphate receptors.

Abstract: Lactam compounds of Formula I and their use for the treatment of neurological and psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorder and insomnia is disclosed.

Abstract: This invention relates to combinations of Compound 1 and Compound 2 which are useful for treating hepatitis C virus infection.

Abstract: Compounds of formula (IA) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.

Abstract: Bisphosphonate compounds and related methods of making and using are disclosed, including pyridinium-1-yl, quinolinium-1-yl, and related compounds. The activity of compounds is disclosed in the context of functional assays such as Leishmania major farnesyl diphosphate synthase (FPPS) inhibition, Dictyostelium discoideum growth inhibition, human gamma delta T cell activation, and bone resorption. The applicability of bisphosphonate compounds in the context of parasitic infections, for example against trypanosomes, is disclosed. Further potential applications of the invention are disclosed regarding the treatment of one or more conditions such as bone resorption disorders, cancer, bone pain, infectious diseases, and in immunotherapy.

Abstract: The invention relates to substituted arylsulphonylaminomethylphosphonic acid derivatives of general formula (I) wherein the groups Ra to Rf, A and Z are defined as mentioned in the specification and claims, which are suitable for preparing a medicament for the treatment of metabolic disorders, particularly type 1 or type 2 diabetes mellitus.

Abstract: The invention provides well-defined aryl and/or heteroaryl substituted indoles that are useful as spingosine-1-phosphate agonists or antagonists. As such, the compounds described herein are useful in treating a wide variety of disorders associated with modulation of sphingosine-1-phosphate receptors.

Abstract: The invention relates to novel and known substituted phosphonates for use in ameliorating amyloid aggregates, particularly for use in the treatment of Alzheimer's disease.

Abstract: The present invention relates to a method for identifying a drug candidate for enhancing expression of p21ctpl/wafl in a human patient suffering from a medical condition that can be treated by enhancing expression of p21C?l/wafl. The method includes (a) providing a cell line comprising a nucleic acid sequence that comprises a p21ctpl/wafl promoter operationally ligated to a reporter domain; (b) exposing the cell line to a compound; and (c) identifying a compound that induces expression of the reporter domain. The compound that induces expression of the reporter domain is a drug candidate for treating a medical condition that can be treated by enhancing expression of p21cipl/wafl.

Abstract: The present invention provides compounds of formula (I), their use as PARP inhibitors as well as pharmaceutical compositions comprising said compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, n, m and X have defined meanings.

Abstract: 2-aryl-4-quinolones are converted into phosphates by reacting with tetrabenzyl pyrophosphate to form dibenzyl phosphates thereof, which are then subject to hydrogenation to replace dibenzyl groups with H, followed by reacting with Amberlite IR-120 (Na+ form) to form disodium salts. The results of preliminary screening revealed that these phosphates showed significant anti-cancer activity. A novel intermediate, 2-selenophene 4-quinolone and ?/, ?/-dialkylaminoalkyl derivatives of 2-phenyl-4-quinolones are also synthesized. These novel intermediates exhibited significant anticancer activities.

Abstract: Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is R is —C(O)—N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a ?-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

Abstract: Compositions and uses associated with the MT477 family of compounds are disclosed. Particular structural features and properties of the compounds are described in detail. Uses include administering an MT477 family member to a patient for therapeutic purposes. Compositions include chemicals belonging to the MT477 family and pharmaceuticals that contain such chemicals.

Abstract: Certain embodiments disclosed relate to compositions, including therapeutic compositions, methods, devices, and systems that modulate at least one inflammatory response or reaction. According to various embodiments, the compositions, methods, devices, and systems relate to modulating one or more of Toll-like receptors, Src family kinases, NF-kB molecules, proteases, or proteasomes.

Abstract: A mutual prodrug of a MRA and a (?-agonist for formulation for delivery by aerosolization to inhibit pulmonary bronchoconstriction is described. The mutual prodrug is preferably formulated in a small volume solution (10-500 ?L) dissolved in a quarter normal saline having pH between 5.0 and 7.0 for the treatment of respiratory tract bronchoconstriction by an aerosol having mass median average diameter predominantly between 1 to 5?, produced by nebulization or by dry powder inhaler.

Abstract: The invention provides methods and compounds for the treatment of neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS (Amyotrophic Lateral Sclerosis), traumatic brain injury, ischemic brain injury or a stroke. In one aspect the compounds are HDAC1 activators. Exemplary HDAC1 activators include metal chelators, iron chelators, deferoxamin, flavonoids, compounds comprising a catechol moity, ginkgetin K, Chembridge 5104434, sciadopilysin, tetrahydrogamboic acid, TAM-11, LY 235959, CGS 19755, SK&F 97541, etidronic acid, levonordefrin, methyldopa, ampicillin trihydrate, D-aspartic acid, gamma-D-glutamylaminomethylsulfonic acid, phenazopyridine to hydrochloride, oxalamine citrate salt, podophyllotoxin, SK&F 97541, (+-)-4-amino-3-(5-chloro-2-thienyl)-butanoic acid, (RS)-(tetrazol-5-yl) glycine, R(+)-SKF-81297, gambogic acid, and derivatives thereof.

Abstract: Methods for disrupting amyloid fibrils in a subject, comprising combining an effective amount of a ?-2 microglobulin fibril disrupting compound with a medium associated with the subject, are disclosed. The invention also relates to combining the ?-2 microglobulin fibril disrupting compound ex vivo with the blood during dialysis treatment of an animal. It also relates to methods for determining which compounds are effective at disrupting amyloid fibrils in a medium.

Abstract: The invention encompasses the novel class of compounds represented by the formula below, which are inhibitors of the PTP-1B enzyme. The invention also encompasses pharmaceutical compositions which include the compounds shown (Formula I) above and methods of treating or preventing PTP-1B mediated diseases, including diabetes.

Abstract: Chemical entities that modulate smooth muscle myosin and/or non-muscle myosin, pharmaceutical compositions and methods of treatment of diseases and conditions associated with smooth muscle myosin and/or non-muscle myosin are described.

Abstract: Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain ether and urea functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.

Abstract: Novel quinolinone farnesyl transferase inhibitors are provided. These new compounds are useful in the treatment or prevention of synucleinopathies, such as Parkinson's Disease, Diffuse Lewy Body Disease, multiple system atrophy, and disorders of brain iron concentration including pantothenate kinase-associated neurodegeneration (e.g., PANK1), or other neurodegenerative/neurological diseases. Provided compounds are also useful in the treatment of proliferative diseases such as cancer, and in the treatment of neurological diseases, such as cognitive impairment, depression, and anxiety. The treatment including administering to a subject a therapeutically effective amount of an inventive farnesyl transferase inhibitor compound.

Abstract: [Problem] To provide a compound having excellent platelet aggregation inhibitory activity. [Means for Resolution] It was found that quinolone derivatives characterized in that these have lower alkyl, cycloalkyl or the like at the 1-position; —N(R0)C(O)-lower alkylene-CO2R0, lower alkylene-CO2R0, lower alkenylene-CO2R0, —O-lower alkylene-CO2R0, —O-(lower alkylene which may be substituted with —CO2R0)-aryl or —O-lower alkenylene-CO2R0 (wherein R0 is H or lower alkyl) at the 3-position; halogen at the 6-position; and amino group substituted with a substituent group having a ring structure at the 7-position, respectively, or pharmaceutically acceptable salts thereof, has excellent P2Y12 inhibitory activity. In addition, it was confirmed that these quinolone derivatives also have excellent platelet aggregation inhibitory activity. Based on the above, these quinolone derivatives or pharmaceutically acceptable salts thereof are useful as platelet aggregation inhibitors.

Abstract: The present invention provides methods and compositions for prophylaxis and treatment of a variety of disorders including DNA damage related disorders, cancer, ischemia, oxidative stress, atherosclerosis, and stroke using a chloroquine compound.

Abstract: Compounds of the formula (I) were synthesized. They were found to down-regulate or inhibit the expression or function of the IGF-1 receptor.

Abstract: Provided herein are phosphadiazine polymerase inhibitor, for example, of any of Formula I, II, III, I?, II?, I?, II?, Ia, IIa, or IIIa, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Abstract: The present invention is directed to a compound of formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof, and methods for treating inflammatory and serine protease mediated disorders.

Abstract: Bisphosphonate compounds and related methods of making and using are disclosed, including pyridinium-1-yl, quinolinium-1-yl, and related compounds. The activity of compounds is disclosed in the context of functional assays such as Leishmania major farnesyl diphosphate synthase (FPPS) inhibition, Dictyostelium discoideum growth inhibition, human gamma delta T cell activation, and bone resorption. The applicability of bisphosphonate compounds in the context of parasitic infections, for example against trypanosomes, is disclosed. Further potential applications of the invention are disclosed regarding the treatment of one or more conditions such as bone resorption disorders, cancer, bone pain, infectious diseases, and in immunotherapy.

Abstract: The invention provides novel phosphoantigen salts and novel crystalline phases of phosphoantigens salts, that the latter including non-solvated polymorphs, and solvates useful as pharmaceuticals. The invention also provides pharmaceutical compositions comprising, and processes for making, novel phosphoantigen crystalline phases. Methods of using such compositions for the treatment of disease, immunostimulatory or immune response modifying use are also provided. The invention also provides method for obtaining phosphoantigen crystals as well as highly pure phosphoantigen compositions.

Abstract: The present invention relates to phosphonated fluoroquinolones, antibacterial analogs thereof, and methods of using such compounds. These compounds are useful as antibiotics for prevention and/or the treatment of bone and joint infections, especially for the prevention and/or treatment of osteomyelitis.

Abstract: Ionic compounds which are liquids at room temperature are formed by the method of mixing a neutral organic liqand with the salt of a metal cation and its conjugate anion. The liquids are hydrophobic, conductive and stable and have uses as solvents and in electrochemical devices.

Abstract: The invention provides a drug combination for the treatment of diseases associated with bone metastasis. The combination provides adenosine or a derivative thereof, a bisphosphonate, and a targeting agent(s) to decrease the signs or symptoms associated with such diseases.

Abstract: The intention relates to bacterial antibiotic resistance and, in particular, to compositions and methods for overcoming bacterial antibiotic resistance. The invention provides novel ?-lactamase inhibitors, which are structurally unrelated to the natural product and semi-synthetic ?-lactamase inhibitors presently available, and which do not require a ?-lactam pharmacophore. The invention also provides pharmaceutical compositions and methods for inhibiting bacterial growth.

Abstract: The invention relates to pharmaceutical compositions for topical administration comprising a topically acceptable antiviral substance and an antiinflammatory glucocorticoid in a pharmaceutically acceptable carrier. The pharmaceutical composition can be used in the prophylactic and curative treatment of herpesvirus infections in mammals including man. The invention also relates to the use of a combination of a topically acceptable antiviral substance and an antiinflammatory glucocorticoid for the manufacture of a medicament for said prophylactic and curative treatment.