Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-1H-pyrazolo[3,4-b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.

The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-1H-pyrazolo[3,4-b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.

Methods of using serum glucocorticoid induced kinase 1 (SGK1) inhibitors for reducing the development of diseases related to salt and water balance, and in particular, hydrocephalus and/or hypertension, are disclosed herein. Particularly, the present disclosure is directed to the use of SGK1 inhibitors to inhibit transepithelial ion transport, such as in one embodiment, in the choroid plexus of a subject, thereby reducing cerebrospinal fluid (CSF) production or, alternatively, in another embodiment, to inhibit transepithelial sodium transport in the kidney collecting duct thereby reducing sodium reabsorption into the blood.

Methods of using serum glucocorticoid induced kinase 1 (SGK1) inhibitors for reducing the development of diseases related to salt and water balance, and in particular, hydrocephalus and/or hypertension, are disclosed herein. Particularly, the present disclosure is directed to the use of SGK1 inhibitors to inhibit transepithelial ion transport, such as in one embodiment, in the choroid plexus of a subject, thereby reducing cerebrospinal fluid (CSF) production or, alternatively, in another embodiment, to inhibit transepithelial sodium transport in the kidney collecting duct thereby reducing sodium reabsorption into the blood.

Compositions and methods for the treatment of tuberculosis, as well as other mycobacterial and gram positive bacterial infections are disclosed. These compositions contain a highly potent and selective oxazolidinone encapsulated with high efficiency to maximize dosing potential of low toxicity drugs, and are stable in the presence of plasma. The compositions are long circulating and retain their encapsulated drug while in the circulation following intravenous dosing to allow for efficient accumulation at the site of the bacterial or mycobacterial infection. The high doses that can be achieved when combined with the long circulating properties and highly stable retention of the drug allow for a reduced frequency of administration when compared to daily or twice daily administrations of other drugs typically utilized to treat these infections.

Compositions and methods for the treatment of tuberculosis, as well as other mycobacterial and gram positive bacterial infections are disclosed. These compositions contain a highly potent and selective oxazolidinone encapsulated with high efficiency to maximize dosing potential of low toxicity drugs, and are stable in the presence of plasma. The compositions are long circulating and retain their encapsulated drug while in the circulation following intravenous dosing to allow for efficient accumulation at the site of the bacterial or mycobacterial infection. The high doses that can be achieved when combined with the long circulating properties and highly stable retention of the drug allow for a reduced frequency of administration when compared to daily or twice daily administrations of other drugs typically utilized to treat these infections.

A medicament for treating hypertension is provided. The medicament has an active ingredient including cannabidiol or a pharmaceutically acceptable salt or ester thereof, and ligustrazine or a pharmaceutically acceptable salt or ester thereof is added to the active ingredient of the medicament. The medicament provided by the present invention has a good therapeutic effect on hypertension and can achieve a significant antihypertensive effect after being administered for a short time. The medicament for treating hypertension provided by the present invention has the advantages of low cost, low toxicity, stable chemical components, and continuous and stable antihypertensive effect.

A medicament for treating hypertension is provided. The medicament has an active ingredient including cannabidiol or a pharmaceutically acceptable salt or ester thereof, and ligustrazine or a pharmaceutically acceptable salt or ester thereof is added to the active ingredient of the medicament. The medicament provided by the present invention has a good therapeutic effect on hypertension and can achieve a significant antihypertensive effect after being administered for a short time. The medicament for treating hypertension provided by the present invention has the advantages of low cost, low toxicity, stable chemical components, and continuous and stable antihypertensive effect.