Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C.sub.5-C.sub.18 alkyl, branched C.sub.5-C.sub.18 alkyl, linear C.sub.2-C.sub.18 alkenyl, branched C.sub.3-C.sub.18 alkenyl, aryl, aryl-C.sub.1-C.sub.18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: (I) wherein Ring A, Ring B, Ring C, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, L, m, n, and p are as defined herein. The compounds are modulators of G-protein coupled receptor 88 (GPR88). Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases mediated by GPR88, including Tourette's Syndrome, Huntington's Disease (HD), Addiction, Parkinson's Disease (PD), Schizophrenia, Alzheimer's disease, and Attention Deficit Hyperactivity Disorder (ADHD).

##STR00001##

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: (I) wherein Ring A, Ring B, Ring C, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, L, m, n, and p are as defined herein. The compounds are modulators of G-protein coupled receptor 88 (GPR88). Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases mediated by GPR88, including Tourette's Syndrome, Huntington's Disease (HD), Addiction, Parkinson's Disease (PD), Schizophrenia, Alzheimer's disease, and Attention Deficit Hyperactivity Disorder (ADHD).

##STR00001##

The present disclosure relates generally to eukaryotic initiation factor 2B modulators of formula A, or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof and methods of making and using thereof.

##STR00001##

The present disclosure relates generally to eukaryotic initiation factor 2B modulators of formula A, or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof and methods of making and using thereof.

##STR00001##

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C.sub.3-C.sub.18 alkyl, branched C.sub.5-C.sub.18 alkyl, linear C.sub.2-C.sub.18 alkenyl, branched C.sub.3-C.sub.18 alkenyl, aryl, aryl-C.sub.1-C.sub.18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.