Described herein are inhibitors Transient Receptor Potential Canonical (TRPC) ion channels comprising TRPC4 protein and/or TRPC5 protein for use in combating obesity and other medical conditions including insulin resistance associated with Type II diabetes or development of Type II diabetes (pre-diabetes), metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Also disclosed is the use of the inhibitors for cosmetic purposes, such as cosmetic weight loss.

The present invention provides a novel heterocyclic derivative or a pharmaceutically acceptable salt thereof. For example, the present invention provides a heterocyclic derivative of the general formula [1] or its tautomer, or a pharmaceutically acceptable salt thereof: ##STR00001##
wherein R.sup.1 and R.sup.2 are the same or different aromatic rings, etc., and ring A is a heterocyclic ring. The compound of the invention or a pharmaceutically acceptable salt thereof has potent mPGES-1 inhibiting activity and is useful as an agent for the treatment or prevention of a disease, such as rheumatoid arthritis, osteoarthritis, temporomandibular joint disorders, low back pain, endometriosis, dysmenorrhea, overactive bladder, malignant tumors or neurodegenerative disease.

The present invention provides a novel heterocyclic derivative or a pharmaceutically acceptable salt thereof. For example, the present invention provides a heterocyclic derivative of the general formula [1] or its tautomer, or a pharmaceutically acceptable salt thereof: ##STR00001##
wherein R.sup.1 and R.sup.2 are the same or different aromatic rings, etc., and ring A is a heterocyclic ring. The compound of the invention or a pharmaceutically acceptable salt thereof has potent mPGES-1 inhibiting activity and is useful as an agent for the treatment or prevention of a disease, such as rheumatoid arthritis, osteoarthritis, temporomandibular joint disorders, low back pain, endometriosis, dysmenorrhea, overactive bladder, malignant tumors or neurodegenerative disease.

The invention provides compounds effective as sphingosine-1-phosphate receptor modulators for treatment of cardiopulmonary diseases, such as hypertension (including malignant hypertension), angina, myocardial infarction, cardiac arrhythmias, congestive heart failure, coronary heart disease, atherosclerosis, angina pectoris, dysrhythmias, cardiomyothopy (including hypertropic cardiomyothopy), heart failure, cardiac arrest, bronchitis, asthma, chronic obstructive pulmonary disease, cystic fibrosis, croup, emphysema, pleurisy, pulmonary fibrosis, pneumonia, pulmonary embolus, pulmonary hypertension, mesothelioma, ventricular conduction abnormalities, complete heart block, adult respiratory distress syndrome, sepsis syndrome, idiopathic pulmonary fibrosis, scleroderma, systemic sclerosis, retroperitoneal fibrosis, prevention of keloid formation, or cirrhosis.

The invention provides compounds effective as sphingosine-1-phosphate receptor modulators for treatment of cardiopulmonary diseases, such as hypertension (including malignant hypertension), angina, myocardial infarction, cardiac arrhythmias, congestive heart failure, coronary heart disease, atherosclerosis, angina pectoris, dysrhythmias, cardiomyothopy (including hypertropic cardiomyothopy), heart failure, cardiac arrest, bronchitis, asthma, chronic obstructive pulmonary disease, cystic fibrosis, croup, emphysema, pleurisy, pulmonary fibrosis, pneumonia, pulmonary embolus, pulmonary hypertension, mesothelioma, ventricular conduction abnormalities, complete heart block, adult respiratory distress syndrome, sepsis syndrome, idiopathic pulmonary fibrosis, scleroderma, systemic sclerosis, retroperitoneal fibrosis, prevention of keloid formation, or cirrhosis.

The present invention relates to sulfonamide compounds of formula (I) and formula (II), or a pharmaceutically acceptable salt thereof. The present sulfonamide compounds are useful non-systemic TGR5 agonists that can be used to treat diabetic diseases in human. The present invention provides a pharmaceutical composition containing sulfonamide compounds of formula (I) and formula (II) and a method of making as well as a method of using same in treating patients inflicted with metabolic disorders by administering same. The compounds of the present invention may be used in combination with additional anti-diabetic drugs. ##STR00001##

The present invention relates to sulfonamide compounds of formula (I) and formula (II), or a pharmaceutically acceptable salt thereof. The present sulfonamide compounds are useful non-systemic TGR5 agonists that can be used to treat diabetic diseases in human. The present invention provides a pharmaceutical composition containing sulfonamide compounds of formula (I) and formula (II) and a method of making as well as a method of using same in treating patients inflicted with metabolic disorders by administering same. The compounds of the present invention may be used in combination with additional anti-diabetic drugs. ##STR00001##

The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to benzimidazole containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with dysregulation of histone deacetylase (HDAC).

The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to benzimidazole containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with dysregulation of histone deacetylase (HDAC).

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.