Abstract: The present invention relates to cannabinoid-2-receptor (CB2R) agonist compounds. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them and to their use as therapeutic agents for the treatment and/or prevention of diseases or conditions in which CB2R stimulation is beneficial (especially inflammatory conditions).

Abstract: The ophthalmic drug delivery vehicles provide comfort and compliance; drug solubility, residence time and permeability; and reduce side effects. In addition, the delivery vehicle can be slightly modified to provide an artificial tear formulation.

Abstract: A method of rapid transbuccal delivery of an active agent into the bloodstream is provided. The method can include providing a pharmaceutical composition comprising the active agent, resin and a volatile solvent and, optionally, water. In some embodiments, the method achieves a Tmax 60 minutes or less, an onset of therapeutic effect of 60 minutes or less, and/or achieves therapeutic serum levels of the active agent within 60 minutes or less. Related compositions also are provided.

Abstract: The invention relates to the prevention and/or treatment of skeletal related disorders using heteroaryl compounds.

Abstract: The present application relates to novel substituted fused pyrimidines and triazines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.

Abstract: The present invention is directed to dihydrochloric acid and dibenzenesulfonic acid salts of the c-Met kinase inhibitor 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)-imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide, and pharmaceutical compositions thereof, useful in the treatment of cancer and other diseases related to the dysregulation of kinase pathways. The present invention further relates to processes and intermediates for preparing 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide, and salts thereof.

Abstract: The present methods and compositions are of use for treatment of conditions involving fibrosis, such as Peyronie's disease plaque, penile corporal fibrosis, penile veno-occlusive dysfunction, Dupuytren's disease nodules, vaginal fibrosis, clitoral fibrosis, female sexual arousal disorder, abnormal wound healing, keloid formation, general fibrosis of the kidney, bladder, prostate, skin, liver, lung, heart, intestines or any other localized or generalized fibrotic condition, vascular fibrosis, arterial intima hyperplasia, atherosclerosis, arteriosclerosis, restenosis, cardiac hypertrophy, hypertension or any condition characterized by excessive fibroblast or smooth muscle cell proliferation or deposition of collagen and extracellular matrix in the blood vessels and/or heart.

Abstract: The present application relates to novel fused pyrimidines and triazines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.

Abstract: Provided are methods of treating or preventing a fungal infection in a subject. The methods comprise identifying a subject with or at risk of developing a fungal infection and administering to the subject a therapeutically effective amount of an inhibitor or a fungal phosphoinositide-dependent kinase 1 (PDK-1) or a homolog thereof. Inhibition of the fungal PDK-1 or homolog thereof results in the treatment or prevention of a fungal infection in the subject. Also provided are compositions comprising an inhibitor of a fungal phosphoinositide-dependent kinase 1 (PDK-1) or a homolog thereof, and a pharmaceutically acceptable carrier.

Abstract: This invention relates to novel substituted 5-(1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives of formula (I) wherein R1 is hydrogen, chloro, methyl or methoxy, R2 is hydrogen or methoxy, with the proviso that at least one of R1 and R2 is other than hydrogen, G1 represents chloro, (C1-C4)-alkyl, (C1-C4)-alkoxycarbonyl, 5-membered aza-heteroaryl, or the group —CH2—OR3, —CH2—NR4R5 or —C(?O)—NR4R6, and G2 represents chloro, cyano, (C1-C4)-alkyl, or the group —CR8AR8B—OH, —CH2—NR2R10, —C(?O)—NR11R12 or —CH2—OR15, having protein tyrosine kinase inhibitory activities, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for treating proliferative disorders, in particular cancer and tumor diseases.

Abstract: The present invention is directed to novel substituted bicyclic aromatic compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.

Abstract: The present invention is directed to a new class of triazine derivatives as described by formula I below in which A, X, R1, R2, R3, and R4 are as defined herein and to the use of the compounds as PDE10 inhibitors.

Abstract: An additive mixture for fuels including a) at least one N-formal, b) at least one antioxidant and c) at least one corrosion inhibitor. The additive mixture ensures that the additized fuels and lubricants have biocidal and corrosion-inhibiting additization, especially when they include proportions of renewable raw materials, such as biodiesel, and when they are in contact with copper-containing surfaces.

Abstract: The present invention relates generally to the field of pharmacogenomics, and more specifically to methods and procedures to determine drug sensitivity in patients to allow the identification of individualized genetic profiles which will aid in selecting cancer patients that are responsive to IGF-1R/IR inhibition.

Abstract: The invention relates to a method of relieving nicotine craving comprising the steps of providing at least one chewing gum comprising tobacco alkaloid to a user, providing relief of nicotine craving to said user by transferring of tobacco alkaloid from the chewing gum to the human body of said user by chewing of said chewing gum, said chewing of said chewing gum comprising a chewing process involving a transfer of tobacco alkaloid from said chewing gum above a threshold transfer rate in the period of about ½ minute to about 2½ minutes from initiation of said chewing process.

Abstract: A compound of formula A having improved non-specific binding characteristics and pharmacokinetic properties is provided: or a pharmaceutically acceptable salt, stereoisomer, or hydrate thereof.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention relates to methods of treating multidrug resistance in cancerous cells with phosphodiesterase (PDE) inhibitors, e.g., PDE5 inhibitors. More specifically, the invention relates to methods of treating multidrug resistance that arises, e.g., during administration of chemotherapeutic/antineoplastic (anticancer) agents for treatment of cancer, with a PDE5 inhibitor (e.g., sildenafil, vardenafil, and tadalafil). The invention also relates to methods of treating cancer, e.g., multidrug resistant cancer, using a PDE5 inhibitor in combination with an antineoplastic therapeutic agent. Further, the invention relates to pharmaceutical compositions for treating multidrug resistant cancers comprising a PDE5 inhibitor, or a combination of a PDE5 inhibitor and an antineoplastic agent.

Abstract: The present invention relates to soluble guanylate cyclase (sGC) and to phosphodiesterases (PDEs) and the pharmacology of sGC stimulators, sGC activators and PDE inhibitors. More particularly, the invention relates to the use of sGC stimulators and sGC activators in combination with PDE5 inhibitors for preparation of medicaments for the treatment of male erectile dysfunction (MED) in particular for the MED treatment of difficult to treat patients and patients not or not fully responding to PDE5 inhibitors.

Abstract: The invention relates to a method for producing medicaments that contain vardenafil hydrochloride, essentially as trihydrate in solid form, and to medicaments that can be obtained according to this method.

Abstract: There is disclosed a formulation for creating a rapid penile erection within 30 minutes. In an embodiment, a lozenge has a preparation configured to create a rapid penile erection. The preparation is effective to create the rapid penile erection with sildenafil citrate in a range of 50-100 mg. The preparation is effective to create the rapid penile erection with tadalafil in a range of 5-40 mg. The preparation is effective to create the rapid penile erection with vardenafil hydrochloride in a range of 5-40 mg. In various embodiments, the formulation includes a solvent configured to permeate skin. Other embodiments are also disclosed.

Abstract: A compound of formula (I) wherein A, R1, R3, and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment of arrhythmia, maintaining normal sinus rhythm, IKur-associated disorders, and other disorders mediated by ion channel function.

Abstract: This invention relates to novel 5-[(hydroxymethyl)aryl]-substituted pyrrolo[2,1-f][1,2,4]triazin-4-amines of formula (I), to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for treating angiogenesis-related disorders, in particular angiogenesis-related ocular disorders.

Abstract: The invention relates to a tobacco alkaloid releasing chewing gum comprising tobacco alkaloid, gum base, and chewing gum ingredients, said gum base comprising elastomer and resin-compounds constituting an amount in the range of about 2 to 20% by weight of said chewing gum.

Abstract: This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and the use of those compounds and compositions for the prevention and/or treatment of hyper-proliferative disorders and diseases associated with angiogenesis.

Abstract: Disclosed is a composition comprising a pyrazino-triazine derivative, an isomer thereof or a pharmaceutically acceptable salt thereof. It is very effective for preventing and treating NSCLC.

Abstract: The present application relates to novel heteroaryl-substituted pyrazolopyridines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.

Abstract: Multifunctional compounds are provided, comprising two or more functional moieties selected from: (i) a moiety that imparts an iron chelator function; (ii) a moiety that imparts a neuroprotective function; (iii) a moiety that imparts combined antiapoptotic, neuroprotective and/or neurorestorative functions; (iv) a moiety that imparts brain MAO inhibition, preferably with little or no MAO inhibition in liver and small intestine; (v) a moiety that imparts cholinesterase inhibitory function; and (vi) a moiety that imparts an N-methyl-D-aspartic acid receptor (NMDAR) inhibition, and pharmaceutically acceptable salts and optical isomers thereof. The multifunctional compounds are useful in the treatment or prevention of diseases, disorders or conditions that can be prevented and/or treated by iron chelation therapy, and/or neuroprotection and/or neurorestoration, and/or apoptosis inhibition and/or MAO inhibition and/or cholinesterase inhibition and/or NMADR inhibition.

Abstract: The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic ?7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

Abstract: Provided are 6-5 membered fused pyridine ring compounds according to Formula (I) or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising these compounds and their use in therapy. In particular, provided is the use of membered fused pyridine ring compounds in the treatment of Bruton's Tyrosine Kinase (Btk) mediated disorders.

Abstract: Methods for treating diseases in humans and vertebrate animals are provided using competitive antagonists of cellular metabolites combined with a protective agent for protecting host cells from toxic effects of the drugs. Also provided are kits comprising competitive antagonists and suitable protective agents. In addition, screening methods for identifying competitive antagonists, protective agents and potentiating agents, for use according to the methods of the invention, are provided.

Abstract: The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) pyrrolotriazines inhibit protein kinase activity thereby making them useful as anticancer agents.

Abstract: The present invention relates to combinations of triazine derivatives and of insulin sensitizers.

Abstract: The present invention is directed to novel substituted bicyclic aromatic compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.

Abstract: The present methods and compositions are of use for treatment of conditions involving fibrosis, such as Peyronie's disease plaque, penile corporal fibrosis, penile veno-occlusive dysfunction, Dupuytren's disease nodules, vaginal fibrosis, clitoral fibrosis, female sexual arousal disorder, abnormal wound healing, keloid formation, general fibrosis of the kidney, bladder, prostate, skin, liver, lung, heart, intestines or any other localized or generalized fibrotic condition, vascular fibrosis, arterial intima hyperplasia, atherosclerosis, arteriosclerosis, restenosis, cardiac hypertrophy, hypertension or any condition characterized by excessive fibroblast or smooth muscle cell proliferation or deposition of collagen and extracellular matrix in the blood vessels and/or heart.

Abstract: A method of treating osteoarthritis by reducing intraosseous hypertension in a patient in need thereof by administering to a patient an effective amount of a composition containing a bone edema medication, such as a vasoactive medication or phosphodiesterase inhibitor, including a PDE-5.

Abstract: The present invention is directed to metabolites of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-ol, the compound of formula (I), pharmaceutical compositions thereof, and to methods of using the metabolites and the pharmaceutical compositions in the treatment of cancer.

Abstract: The present invention relates to a process for the preparation of a medicament containing vardenafil hydrochloride trihydrate in solid form, in which vardenafil hydrochloride trihydrate is processed with suitable pharmaceutical auxiliaries at a temperature of from approx. 20° C. to approx. 45° C.

Abstract: The present application relates to novel drug formulations of vardenafil which dissolve rapidly in the mouth and lead to increased bioavailability and to a plateau-like plasma concentration profile, and to processes for their preparation.

Abstract: A compound of formula (I): wherein all symbols have the same meanings as defined in the specification; a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug thereof, has a Btk inhibitory activity, and is useful as a method for preventing and/or treating a rheumatoid arthritis, an autoimmune disease, a B cell lymphoma of cancer, and the like.

Abstract: Disclosed is a composition effective in reducing skin wrinkles. The composition comprises or uses a phosphodiesterase 5 (PDE5) inhibitor as an active ingredient. Further disclosed is a method for reducing skin wrinkles using the composition.

Abstract: The present application relates to novel substituted imidazopyridines and imidazopyridazines, to processes for their preparation, to their use, alone or in combinations, for the treatment and/or prophylaxis of diseases and to their use for the production of medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.

Abstract: The present application provides compounds that are useful as MCHR1 antagonists, especially for the treatment of obesity, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I wherein the variables are defined herein.

Abstract: New pyrrolotriazinone derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks).

Abstract: There is provided compositions and methods for the treatment of respiratory conditions such as pulmonary hypertension and sickle-cell disease in a patient in need thereof. The composition and method are for treating a patient in need thereof by inhalation of a composition containing amino acid ester compounds comprising at least one nitric oxide releasing group and pharmaceutical salts thereof.

Abstract: This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, pulmonary inflammation, acute respiratory distress syndrome, periodontitis, multiple sclerosis, gingivitis, gingivitis, atherosclerosis, dry eye, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and pounds.

Abstract: The invention relates to a product containing the compound of formula (I) below (I) or a pharmaceutically acceptable salt of this compound, in combination with at least one compound having PDE5-inhibitory properties, or a pharmaceutically acceptable salt thereof, for therapeutic use, simultaneously, separately or over a period of time, in the treatment of a disease wherein vasoconstriction is involved.

Abstract: Compounds, methods, and compositions for the treatment of infections in or exposure to humans and other host animals of Flaviviridae viruses, including HCV, that includes the administration of an effective amount of a spiro[2.4]heptane as described herein or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier, are provided. The spiro[2.4]heptane compounds either possess antiviral activity, or are metabolized to a compound that exhibits such activity.

Abstract: Conformationally constrained compounds that mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins are disclosed. Such reverse-turn mimetic structures have utility over a wide range of fields, including use as diagnostic and therapeutic agents. Libraries containing the reverse-turn mimetic structures of this invention are also disclosed as well as methods for screening the same to identify biologically active members. The invention also relates to the use of such compounds for inhibiting or treating disorders modulated by Wnt-signaling pathway, such as cancer, especially colorectal cancer, restenosis associated with angioplasty, polycystic kidney disease, aberrant angiogenesis disease, rheumatoid arthritis disease, tuberous sclerosis complex, Alzheimer's disease, excess hair growth or loss, or ulcerative colitis.

Abstract: The present invention provides heteroaromatic derivatives and pharmaceutical acceptable salts and formulations thereof useful in modulating the protein kinase activity, especially phosphatidylinositol 3-kinases (PI3 kinases) and mTOR, and in modulating inter- and/or intra-cellular signaling activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.