Abstract: Novel CFTR corrector compounds that are effective in rescuing halide efflux in a cell are provided. Also provided are methods for treating protein folding disorders (e.g., cystic fibrosis). The methods include administering a CFTR corrector compound or pharmaceutically acceptable salt or prodrug thereof. Methods of screening for CFTR corrector compounds are also described herein. The methods of screening include contacting a cell that endogenously expresses a CFTR mutation with the compound to be screened and detecting a rescue of halide efflux from the cell.

Abstract: Disclosed are methods for treating Vascular Leak Syndrome. Further disclosed are methods for treating vascular leakage due to inflammatory diseases, inter alia, sepsis, lupus, irritable bowel disease. Yet further disclosed are methods for treating renal cell carcinoma and melanoma. Still further disclosed are methods for reducing metastasis of malignant cells and/or preventing the proliferation of carcinoma cells via spreading due to vascular leakage.

Abstract: A method of treating a movement abnormality associated with the pathology of a neurological movement disorder, such as Parkinson's disease or Restless Leg(s) Syndrome by administering a therapeutically effective amount of a PDE7 inhibitory agent. An aspect of the invention provides for the administration of a PDE& inhibitory agent in conjunction with a dopamine agonist or precursor, such as levodopa. In another aspect of the invention, the PDE7 inhibitory agent may be selective for PDE7 relative to other molecular targets (i) known to be involved with the pathology of Parkinson's disease or (ii) at which other drug(s) that are therapeutically effective to treat Parkinson's disease act.

Abstract: Compositions that are effective in inhibiting gamma-glutamyl transpeptidase are disclosed. Methods of producing and using these compositions are also disclosed.

Abstract: This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders.

Abstract: Compounds which modulate the CB2 receptor are disclosed. Compounds according to the invention bind to and are agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain (I).

Abstract: The present invention relates generally to the field of therapy. The invention particularly relates to insulin sensitisers and methods of regulating glucose homeostasis and to the therapeutic or prophylactic treatment of diseases and associated conditions, in which impaired glucose uptake due to insulin resistance is involved or implicated, such as diabetes, syndrome X, hyperglycaemia, vascular disease and kidney disease. The present invention further relates to compounds and agents and compositions thereof for use in the treatment methods.

Abstract: This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders.

Abstract: The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of liver X receptors (LXRs).

Abstract: The present invention is directed to a method of treating a subject for a pulmonary disease by administering a therapeutically effective amount of a compound of the formula: wherein R1, R2 or R3 are each independently a C1 to C6 alkyl, a halogen, a sulfate, or a phosphate. The pulmonary disease in the subject can be hypoxic pulmonary vasoconstriction, pulmonary edema, pulmonary hypertension, asthma, chronic obstructive pulmonary disease, cystic fibrosis, interstitial fibrosis, high altitude residence, sleep apnea syndrome, atrial septal defects, and pulmonary diseases associated with other conditions. If this same compound is modified so that R1, R2 or R3 each independently is a C1 to C6 alkyl and the compound is not a carbonic acid inhibitor, it can be administered to a subject to block hypoxic pulmonary vasoconstriction and/or prevent high altitude pulmonary edema.

Abstract: Disclosed are compounds of Formula I: and the pharmaceutically acceptable salts thereof, wherein “A” is S—; —SO—, —SO2—, —O— or NRa-, and Ra, and R1 through R5 are defined herein. Also disclosed are pharmaceutical formulations comprising a compound of Formula I and methods of treating, managing, or ameliorating diseases amenable to treatment, management, or amelioration by inhibition of LRRK2 kinase activity, for example, Parkinson's disease.

Abstract: Disclosed are methods for treating Vascular Leak Syndrome. Further disclosed are methods for treating vascular leakage due to inflammatory diseases, inter alia, sepsis, lupus, irritable bowel disease. Yet further disclosed are methods for treating renal cell carcinoma and melanoma. Still further disclosed are methods for reducing metastasis of malignant cells and/or preventing the proliferation of carcinoma cells via spreading due to vascular leakage.

Abstract: The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treatment using the novel heterocyclic compounds of the invention.

Abstract: The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein R?1, X, X?, L and Y are defined herein. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Abstract: Biocompatible intraocular drug delivery systems include a carbonic anhydrase inhibitor therapeutic agent and a polymeric component in the form of an implant, a microparticle, a plurality of implants or microparticles, and combinations thereof. The therapeutic agent is released in a biologically active form, for example, the therapeutic agent may retain its three dimensional structure when released into an eye of a patient, or the therapeutic agent may have an altered three. The implants may be placed in an eye to treat or reduce the occurrence of one or more ocular conditions, such as retinal damage, including glaucoma and proliferative vitreoretinopathy among others.

Abstract: This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders.

Abstract: Compounds of the formula I in which R1, R2, R3 and R4 have the meanings indicated in Claim 1, are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumours.

Abstract: The invention relates to N-arylaminomethylenebenzothiophenones of General Formula (I) for use as a drug for the treatment of cardiovascular diseases: wherein E is S, O, or CH2, D is CH or NH, and Ar is a phenyl or naphtyl moiety substituted by an electron-withdrawing group, an unsubstituted heteroaryl residue, or a heteroaryl residue substituted by alkyl or an electron-withdrawing group.

Abstract: The invention relates to compounds of formula (I): useful for treating disorders mediated by acyl coA-diacylglycerol acyl transferase 1 (DGAT1), e.g. metabolic disorders. The invention also provides methods of treating such disorders, and compounds and compositions etc. for their treatment.

Abstract: The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of liver X receptors (LXRs).

Abstract: There is provided compounds of formula (I), wherein Z, M, R1, X, R2, R3 and B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein kinase (e.g. a PIM family kinase or PI3-K) is desired and/or required, and particularly in the treatment of cancer.

Abstract: Certain multi-cyclic compounds and compositions thereof are useful for reducing or inhibiting the growth of bacterial biofilms and for controlling bacterial biofilm infections. Such compounds and compositions are also useful in methods for reducing or inhibiting the growth of biofilms and for controlling bacterial biofilm infections involving biofilms.

Abstract: Premature termination codons readthrough compounds, composition thereof, and methods of making and using the same are provided.

Abstract: This disclosure is directed to treatment of addictions and primary impulse-control disorders using phosphodiesterase 7 (PDE7) inhibitors, alone or in combination with other therapeutic agents.

Abstract: The invention relates to compounds of the formula (I) either (i) in the state of a base or an acid addition salt, or (ii) in the state of an acid or a base addition salt, as well as to a method for preparing same and to the therapeutic applications thereof.

Abstract: The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Abstract: The present invention is directed to the use of a compound of formula (I) or pharmaceutically acceptable salt thereof, for the treatment of disorders mediated by the melanocortin-5 receptor, particularly dermatological disorders; and further directed to pharmaceutical compositions containing the compound of formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection. Thus, in one specific aspect the invention relates to formulas (II), (III), (IV), (V), (VI), (VII), (VIII), (IX).

Abstract: A compound of Formula (I) wherein: either X is N and Y is CR5 or X is C and Y is S; Z is selected from N and CH; R1 is selected from H and Me; R2 is selected from H, OH, OMe and Me; each R3 is independently selected from C1-3alkyl, F, Cl, Br, CF3 and NH2; R4 is selected from Me, CF3, NO2 and CHF2; R5 is selected from H, Me and CHF2; R6 is selected from H and Me; and p is 0-3, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.

Abstract: Novel Alpha-halo- and Alpha-alkyl-cyclopropylcarboxy compounds, and uses of these and related compounds in the treatment of a variety of neurological diseases and disorders, and particularly epilepsy, are provided.

Abstract: The present invention relates to compounds useful as inhibitors of voltage-gated sodium channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

Abstract: The present invention concerns 2-oxo-1-pyrrolidine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.

Abstract: The invention relates to compositions and methods for inhibiting RNA binding proteins (e.g., MEX-3, MEX-5 and POS-1), as well as methods for treating and preventing disorders associated with parasitic infections and inflammatory disorders.

Abstract: Disclosed herein are compositions and methods for the treatment of otic diseases or conditions with antimicrobial agent compositions and formulations administered locally to an individual afflicted with an otic disease or condition, through direct application of these compositions and formulations onto or via perfusion into the targeted auris structure(s).

Abstract: Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

Abstract: A compound of Formula (I) or a pharmaceutically acceptable salt thereof: Wherein: Het is a 5 to 10-membered heteroaromatic ring; Either X is N and Y is CR5; or X is C and Y is S; Z is selected from N and CH; R1 is selected from H and C1-2alkyl; R2 is selected from H, C1-2alkyl, OH, —CH2OH and C1-2alkoxy; Each R3 is independently selected from OH, C1-3alkyl, F, Cl, Br, NH2, and C1-3alkoxy; R4 is selected from C1-3alkyl and haloC1-3alkyl; R5 is selected from H, C1-3alkyl and haloC1-3alkyl; R6 and R7 are either i) each independently selected from H, C1-3alkyl and C1-3alkoxy; or ii) R6 and R7 together with the ring to which they are attached form a 9-membered bicyclic ring; p is 0-3; and RA is selected from H and C1-3alkyl, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.

Abstract: Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

Abstract: The present application relates to novel bisaryl-linked 5-aryl-1,2,4-triazolone derivatives, to processes for preparing them, to their use alone or in combinations for the treatment and/or prevention of diseases and also to their use for the production of medicaments for the treatment and/or prevention of diseases, more particularly for the treatment and/or prevention of cardiovascular disorders.

Abstract: Disclosed herein are compounds of formula (I) wherein Ring A and R1 are as defined in the specification. Pharmaceutical compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and pharmaceutical compositions are also disclosed.

Abstract: The present invention relates to novel heterocyclic compounds, including oxadiazole compounds, pharmaceutical compositions and their use in the inhibition of reverse transcriptase and the treatment of HIV (1 and 2) infections, AIDS and ARC and other viral infections.

Abstract: The present invention aims to provide a glucokinase activator useful as a pharmaceutical agent such as an agent for the prophylaxis or treatment of diabetes, obesity and the like, and the like. A glucokinase activator containing a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.

Abstract: Pleckstrin homology domain binding compounds, pharmaceutical compositions including such compounds, and methods for their use are described herein.

Abstract: The present invention relates to compounds useful as inhibitors of voltage-gated sodium channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

Abstract: Compounds of formula (I) and formula (II) are disclosed. Compounds according to the invention bind to and are agonists, antagonists or inverse agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.

Abstract: Provided is a pharmaceutical composition including as an active component a compound of formula (I): wherein X and (R1)n are as defined, and a physiological acceptable carrier. Also provided is a method for treating cancer including administering to an individual in need of such treatment an effective amount of the presently described pharmaceutical composition.

Abstract: The method of treating impaired wound healing in diabetics comprises the step of administering an effective amount of a glycogen synthase kinase 3-? (GSK-3?) inhibitor to a diabetic patient in need thereof to activate the NF-E2-related factor 2 (Nrf2) and genes downstream of Nrf2 that normally regulate the expression and coordination of antioxidant responses during wound healing, but are suppressed in the diabetic patient undergoing the oxidative stress that can occur during wound healing. The GSK-3? inhibitor may be lithium or a pharmaceutically acceptable salt thereof, or TDZD-8 (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione). The method may further comprise the step of testing the diabetic patient for the presence of oxidative stress and decreased Nrf2, which enables the early or prophylactic treatment of the patient with a GSK-3? inhibitor when the patient first presents with a wound, rather than waiting for other symptoms of impaired wound healing to occur.

Abstract: The present invention is directed to ?-ketoamide derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by endothelial lipase, for example, cardiovascular disorders.

Abstract: The present invention is directed to compounds for use in the treatment or prevention of influenza virus infection.

Abstract: Compounds represented by formula I: or pharmaceutically acceptable salts and solvates thereof, wherein A, B, B?, X, Y, R1, R1?, R2, R2?, R3, R3?, R5, R5?, R6, m, n, or p are as defined herein, are useful for treating flaviviridae viral infections.

Abstract: The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treatment using the novel heterocyclic compounds of the invention.