The present invention is directed to the compounds of Formula I which are inhibitors of tropomyosin-related kinase A (TrkA): Formula (I) or steroisomers, tautomers or a pharmaceutically acceptable salts, metabolites, isotopes, solvates or prodrugs thereof, wherein, Ra, Rb, Rc, Rd, R1, R2, L and Het-Ar are as defined herein. These compounds can be used for the preventive and/or therapeutic treatment of diseases or disorders associated with abnormal activities of nerve growth factor (NGF) receptor TrkA such as Pain, inflammation or an inflammatory diseases, Cancer, atherosclerosis, restenosis, thrombosis, Neurodegenerative diseases, Erectile Dysfunction (ED), Skin disorders, Autoimmune disease like Multiple sclerosis, Sjögren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis, Infectious diseases, diseases related to an imbalance of the regulation of bone remodeling, endometriosis, pelvic pain syndrome and diseases resulting from abnormal tissue remodelling and fibrotic disorders; or a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination.

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The present invention relates to a pharmaceutical composition comprising a combination of an FXR agonist and at least one lipid lowering agent (e.g., PPAR-alpha agonist, PPAR-delta agonist, PPAR-alpha and delta dual agonist, and/or statin). Also disclosed is use of the combination for the treatment or prevention of a FXR mediated disease or condition, such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), portal hypertension, bile acid diarrhea, NAFLD (nonalcoholic fatty liver disease), NASH (non-alcohol-induced steatohepatitis), and other chronic liver diseases. The combination of the present invention is useful for the treatment or prevention of conditions related to elevated lipid and liver enzyme levels. The present invention also relates to packs or kits including the pharmaceutical combination.

Provided are a method for efficiently manufacturing a nitrogen-containing compound, which is used for manufacturing a treatment agent for integrin-related diseases, or a salt thereof and a manufacturing intermediate of the compound or a salt thereof.

A method for manufacturing a novel nitrogen-containing compound or a salt thereof includes (1) a step of obtaining a compound represented by Formula [10] or a salt thereof through an amidation reaction; and (2) a step of deprotecting the compound represented by Formula [10] or a salt thereof.

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Compositions including the combination of cremastranone analogs and anti-angiogenic agents and the use of the compositions for targeting ocular angiogenesis such as seen in neovascular eye diseases are disclosed.

The present invention relates to a method of converting human fibroblasts into neural stem cells, and more particularly, to a method of directly converting human fibroblasts into neural stem cells using only a combination of small-molecule compounds without any introduction of a foreign gene, and to the use of the neural stem cells. The method of directly converting human fibroblasts into neural stem cells using only small-molecule compounds without any introduction of a foreign gene makes it possible to obtain genetically stable neural stem cells in an amount sufficient for use in cell therapy by deriving them from human fibroblasts. The neural stem cells obtained according to the method of the present invention can differentiate into functional neural cells and are not tumorigenic. Thus, these neural stem cells are useful as cellular therapeutic agents for treatment of brain diseases.

Disclosed are compounds of formulae I and II, and pharmaceutically acceptable salts and prodrugs thereof, which are inhibitors of the complement system. Also provided are pharmaceutical compositions comprising such a compound, and methods of using the compounds and compositions in the treatment or prevention of a disease or condition characterized by aberrant complement system activity. ##STR00001##

This invention relates to isolated polypeptides that are glucagon-receptor selective analogs and peptide derivatives thereof. These analogs are selective for human glucagon receptor with improved solubility, thermal stability, and physicochemical properties as compared to native endogenous glucagon. This invention also relates to methods of using such polypeptides in a variety of therapeutic and diagnostic indications, as well as methods of producing such polypeptides. These analogs are useful, alone or in combination with other therapeutic peptides, in methods of treating obesity, diabetes, metabolic disorders, and other disorders or disease.

Disclosed are compounds of formula I: ##STR00001## as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one such compound, and methods involving use of the compounds and compositions in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.

The present invention relates to a process for the preparation of pirfenidone, an immunosuppressive drug developed for the treatment of idiopathic pulmonary fibrosis.

Provided herein are compounds of the formulas: ##STR00001##
wherein: n, X.sub.2, R.sub.3, R.sub.3′, R.sub.4, R.sub.4′, R.sub.5, R.sub.5′, R.sub.6, and R.sub.6′ are as defined herein. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including diabetic peripheral neuropathy or cancer.